| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| A Multicenter, Randomized, Open-Label Phase 3 Study to Investigate the Efficacy and Safety of Aldoxorubicin Compared to Investigator's Choice in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcomas Who Either Relapsed or Were R [NCT02049905] | Phase 3 | 433 participants (Actual) | Interventional | 2014-01-31 | Completed |
| A Phase III Multicenter, International, Randomized, Double-blind, Placebo-controlled Study of Doxorubicin Plus Palifosfamide-tris vs. Doxorubicin Plus Placebo in Patients With Front-line Metastatic Soft Tissue Sarcoma. [NCT01168791] | Phase 3 | 447 participants (Actual) | Interventional | 2010-07-31 | Completed |
| A Phase I Multicenter, Open-label Study of the Effect on QTc, Pharmacokinetics, Safety, and Preliminary Efficacy of Single-agent Palifosfamide-tris in Subjects With Advanced Solid Tumors [NCT01340547] | Phase 1 | 24 participants (Anticipated) | Interventional | 2011-06-30 | Active, not recruiting |
| Apatinib+Ifosfamide and Etoposide (IE) Versus IE Alone for Relapsed or Refractory Osteosarcoma: a Real-world Study in Two Centers in China [NCT04690231] | | 79 participants (Actual) | Interventional | 2020-12-01 | Completed |
| Localized High-Risk Soft Tissue Sarcomas Of The Extremities And Trunk Wall In Adults: An Integrating Approach Comprising Standard Vs Histotype-Tailored Neoadjuvant Chemotherapy [NCT01710176] | Phase 3 | 550 participants (Actual) | Interventional | 2011-06-01 | Active, not recruiting |
| A Randomized Phase 2 Trial of Brentuximab Vedotin (SGN35, NSC# 749710), or Crizotinib (NSC#749005, Commercially Labeled) in Combination With Chemotherapy for Newly Diagnosed Patients With Anaplastic Large Cell Lymphoma (ALCL) [NCT01979536] | Phase 2 | 137 participants (Actual) | Interventional | 2013-11-13 | Active, not recruiting |
| A Pilot Phase II Study for Children With Infantile Fibrosarcoma [NCT00072280] | Phase 2 | 7 participants (Actual) | Interventional | 2004-11-30 | Terminated(stopped due to Due to poor accrual) |
| A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LLy) [NCT02112916] | Phase 3 | 847 participants (Actual) | Interventional | 2014-10-04 | Active, not recruiting |
| A Phase 2 Trial of Chemotherapy Followed by Response-Based Whole Ventricular &Amp; Spinal Canal Irradiation (WVSCI) for Patients With Localized Non-Germinomatous Central Nervous System Germ Cell Tumor [NCT04684368] | Phase 2 | 160 participants (Anticipated) | Interventional | 2021-07-13 | Recruiting |
| Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT) [NCT04322318] | Phase 2 | 221 participants (Anticipated) | Interventional | 2020-10-19 | Recruiting |
| International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Testing Imatinib in Combination With Two Different Cytotoxic Chemotherapy Backbones [NCT03007147] | Phase 3 | 475 participants (Anticipated) | Interventional | 2017-08-08 | Recruiting |
| Pazopanib Neoadjuvant Trial in Non-Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS): A Phase II/III Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib (NSC# 737754) [NCT02180867] | Phase 2/Phase 3 | 140 participants (Actual) | Interventional | 2014-07-11 | Active, not recruiting |
| Presurgical Chemotherapy Compared With Immediate Surgery and Adjuvant Chemotherapy for Nonmetastatic Osteosarcoma of the Pelvis and Sacrum [NCT03360760] | | 100 participants (Anticipated) | Interventional | 2018-08-01 | Recruiting |
| (RICE) Plus Bortezomib (Velcade) in a Dose-Escalating Fashion for Patients With Relapsed or Primary Refractory Aggressive B-Cell NHL [NCT01300793] | Phase 1 | 6 participants (Actual) | Interventional | 2007-05-31 | Terminated(stopped due to closed for low accrual and no data is available.) |
| Feasibility and Dose Discovery Analysis of Zoledronic Acid With Concurrent Chemotherapy in the Treatment of Newly Diagnosed Metastatic Osteosarcoma [NCT00742924] | Phase 1 | 24 participants (Actual) | Interventional | 2008-08-31 | Completed |
| Phase II Trial of Pembrolizumab in Combination With ICE Salvage Chemotherapy for Relapsed/Refractory Hodgkin Lymphoma [NCT03077828] | Phase 2 | 43 participants (Actual) | Interventional | 2017-04-21 | Active, not recruiting |
| A Treatment Strategy of the Use of 1st Line Chemotherapy in Patients With Poor-Prognosis Disseminated Non-Seminomatous Germ Cell Tumors Based on Tumor Marker Decline: A Phase II Trial of Paclitaxel, Ifosfamid and Cisplatin Regimen. [NCT02414685] | Phase 2 | 19 participants (Actual) | Interventional | 2015-04-30 | Completed |
| A Study of Etoposide and Ifosfamide Combined With or Without Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma [NCT05590572] | Phase 1/Phase 2 | 148 participants (Anticipated) | Interventional | 2023-01-31 | Not yet recruiting |
| Multicentric, Randomized Phase II Trial for the Treatment of Patients With Relapsed Osteosarcoma [NCT02718482] | Phase 2 | 7 participants (Actual) | Interventional | 2016-04-06 | Terminated(stopped due to Not adequate enrollment (sample size not possible to reach)) |
| A Phase III Randomised Study Comparing Three Combination Chemotherapy Regimens in Patients With Non Pre-treated Advanced Non-small Cell Lung Cancer [NCT00622349] | Phase 3 | 707 participants (Actual) | Interventional | 2004-02-29 | Completed |
| A Phase II Multicenter, Parallel Group, Randomized Study of Palifosfamide Tris Plus Doxorubicin Versus Doxorubicin in Subjects With Unresectable or Metastatic Soft-tissue Sarcoma [NCT00718484] | Phase 2 | 67 participants (Actual) | Interventional | 2008-08-31 | Active, not recruiting |
| Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma [NCT02306161] | Phase 3 | 312 participants (Actual) | Interventional | 2014-12-12 | Active, not recruiting |
| Mobilization of Autologous Peripheral Blood Stem Cells (PBSC) in CD20+ Lymphoma Patients Using RICE, G-CSF (Granulocyte-Colony Stimulating Factor), and Plerixafor [NCT01097057] | Phase 2 | 20 participants (Actual) | Interventional | 2010-11-09 | Completed |
| A Phase 2 Study of Polatuzumab Vedotin With Rituximab, Ifosfamide, Carboplatin, and Etoposide (PolaR-ICE) as Initial Salvage Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma [NCT04665765] | Phase 2 | 41 participants (Actual) | Interventional | 2021-01-18 | Active, not recruiting |
| A Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Ifosfamide Plus Paclitaxel in Chemotherapy-Naive Patients With Newly Diagnosed Stage I-IV, Persistent or Recurrent Carcinosarcoma (Mixed Mesodermal Tumors) of the Uterus, Fallopian Tube, P [NCT00954174] | Phase 3 | 637 participants (Actual) | Interventional | 2009-08-17 | Active, not recruiting |
| A Scandinavian Sarcoma Group Treatment Protocol for Adult Patients With Non-metastatic High-risk Soft Tissue Sarcoma of the Extremities and Trunk Wall [NCT00790244] | Phase 2 | 188 participants (Anticipated) | Interventional | 2007-10-31 | Recruiting |
| Intensified Tyrosine Kinase Inhibitor Therapy (Dasatinib NSC# 732517) in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL) [NCT00720109] | Phase 2/Phase 3 | 63 participants (Actual) | Interventional | 2008-07-14 | Completed |
| An Open, Single-arm, Multi-center Clinical Trial of Molecular Subtype-guided R-MINE+X Regimen in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) [NCT05784987] | | 60 participants (Anticipated) | Interventional | 2023-04-15 | Not yet recruiting |
| Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma [NCT00354744] | Phase 3 | 109 participants (Actual) | Interventional | 2006-07-31 | Completed |
| High-dose Chemotherapy and Autologous Stem Cell Transplant or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma - Randomized Phase III Trial [NCT02531841] | Phase 3 | 250 participants (Anticipated) | Interventional | 2014-07-31 | Recruiting |
| Treatment of Recurrent or Resistant Pediatric Malignant Germ Cell Tumors With Paclitaxel, Ifosfamide and Carboplatin [NCT00467051] | Phase 2 | 20 participants (Actual) | Interventional | 2007-11-05 | Completed |
| A Phase II Study To Assess The Ability Of Neoadjuvant Chemotherapy Plus/Minus Second Look Surgery To Eliminate All Measurable Disease Prior To Radiotherapy For NGGCT [NCT00047320] | Phase 2 | 104 participants (Actual) | Interventional | 2004-01-31 | Completed |
| A Phase I Study of Oral Palifosfamide Tris in Advanced, Refractory, Solid Tumors [NCT00607711] | Phase 1 | 20 participants (Anticipated) | Interventional | 2008-03-31 | Suspended(stopped due to IND was withdrawn) |
| SIOP CNS GCT II: Prospective Trial for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Intracranial Germ Cell Tumors [NCT01424839] | Phase 4 | 400 participants (Anticipated) | Interventional | 2011-10-31 | Recruiting |
| Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index Low-Intermediate Risk, High-Intermediate Risk, or High Risk Diffuse Large B Cell Lymphoma [NCT00712582] | Phase 2 | 96 participants (Actual) | Interventional | 2008-07-01 | Completed |
| A Phase I Study of Intravenous (IV) Palifosfamide-tris Administered in Combination With IV Etoposide and IV Carboplatin in Patients With Malignancies for Which Etoposide and Carboplatin Are an Appropriate Choice [NCT01242072] | Phase 1 | 12 participants (Anticipated) | Interventional | 2010-11-30 | Active, not recruiting |
| Magnetic Resonance Based Non-Invasive Thermometry for Hyperthermic Treatment of Extremity Soft Tissue Sarcomas: A Multimodal Phase I/II Study [NCT00093509] | Phase 1/Phase 2 | 15 participants (Actual) | Interventional | 1999-11-30 | Completed |
| A Pilot Study to Evaluate Novel Agents (Temozolomide and Cixutumumab [IMC-A12, Anti-IGF-IR Monoclonal Antibody NSC # 742460]) in Combination With Intensive Multi-agent Interval Compressed Therapy for Patients With High-Risk Rhabdomyosarcoma [NCT01055314] | Phase 2 | 175 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Phase 1/2 Study of Lenvatinib in Children and Adolescents With Refractory or Relapsed Solid Malignancies and Young Adults With Osteosarcoma [NCT02432274] | Phase 1/Phase 2 | 117 participants (Actual) | Interventional | 2014-12-29 | Completed |
| A Multi-center, Open-Label, Adaptive, Randomized Study of Palifosfamide-tris, a Novel DNA Crosslinker, in Combination With Carboplatin and Etoposide (PaCE) Chemotherapy Versus Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients With Extens [NCT01555710] | Phase 3 | 548 participants (Anticipated) | Interventional | 2012-05-31 | Active, not recruiting |
| Pilot Trial of an Implantable Microdevice for In Vivo Drug Sensitivity Testing in Patients With Sarcomas [NCT04199026] | Early Phase 1 | 20 participants (Anticipated) | Interventional | 2024-01-31 | Not yet recruiting |
| A Randomized Study Comparing Chemotherapy Followed by G-CSF Alone Versus G-CSF Plus GM-CSF for Mobilization of Peripheral Blood Stem Cells in Patients With Non-Hodgkin's Lymphomas [NCT00499343] | Phase 2 | 84 participants (Actual) | Interventional | 2004-01-31 | Completed |
| A European Treatment Protocol for Bone-sarcoma in Patients Older Than 40 Years [NCT02986503] | | 100 participants (Actual) | Observational | 2002-01-31 | Completed |
| Randomized Phase III Trial of Chemotherapy vs. Pembrolizumab Plus Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma [NCT05711628] | Phase 3 | 0 participants (Actual) | Interventional | 2023-08-10 | Withdrawn(stopped due to Other - Protocol moved to Withdrawn) |
| A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma [NCT01231906] | Phase 3 | 642 participants (Actual) | Interventional | 2010-11-22 | Active, not recruiting |
| A Phase II Trial of Response-Adapted Second-Line Therapy for Hodgkin Lymphoma Using Anti-PD-1 Antibody Nivolumab ? ICE Chemotherapy as a Bridge to Autologous Hematopoietic Cell Transplant (NICE Trial) [NCT03016871] | Phase 2 | 78 participants (Actual) | Interventional | 2017-04-24 | Active, not recruiting |
| A Phase I Study Combining Ibrutinib With Rituximab, Ifosfamide, Carboplatin, and Etoposide (R-ICE) in Patients With Relapsed or Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL) [NCT02219737] | Phase 1 | 26 participants (Actual) | Interventional | 2014-09-12 | Completed |
| A Randomized Controlled Multi-center Clinical Trial on Treatment of Stage I/II NK/T Cell Lymphoma With DDGP Regiment (Gemcitabine,Pegaspargase,Cisplatin,Dexamethasone) [NCT01501136] | Phase 4 | 200 participants (Anticipated) | Interventional | 2011-01-31 | Recruiting |
| A Phase II Study of Sorafenib With Chemotherapy, Radiation, and Surgery for High-Risk Soft Tissue Sarcomas [NCT02050919] | Phase 2 | 20 participants (Actual) | Interventional | 2013-12-03 | Completed |
| A Phase II Randomized, Open Label Study of Ad-RTS-hIL-12 Monotherapy or Combination With Palifosfamide in Subjects With Recurrent/Metastatic Breast Cancer and Accessible Lesions [NCT01703754] | Phase 2 | 12 participants (Actual) | Interventional | 2013-03-31 | Completed |
| A Phase I Study of Avelumab Plus Utomilumab-Based Combination Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma [NCT03440567] | Phase 1 | 16 participants (Anticipated) | Interventional | 2018-04-02 | Active, not recruiting |
| Phase I/Ib Study of Carfilzomib Plus Rituximab Plus Ifosfamide Plus Carboplatin Plus Etoposide (C-R-ICE) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) [NCT01959698] | Phase 1 | 29 participants (Actual) | Interventional | 2014-04-17 | Active, not recruiting |
| A Randomized Phase II Study of Bortezomib Plus ICE (BICE) Versus Standard ICE for Patients With Relapsed/Refractory Classical Hodgkin Lymphoma [NCT00967369] | Phase 2 | 20 participants (Actual) | Interventional | 2009-08-24 | Completed |
| Effects of Rolapitant on Nausea/Vomiting in Patients With Sarcoma Receiving Multi-Day Highly Emetogenic Chemotherapy (HEC) With Doxorubicin and Ifosfamide Regimen (AI) [NCT02732015] | Phase 2 | 37 participants (Actual) | Interventional | 2016-10-12 | Terminated(stopped due to Terminated per PI's request) |
| Single-center, Open, Non-randomized, Phase II Prospective Study of Apatinib Combined With Chemotherapy in the Treatment of Unresectable Soft Tissue Sarcoma [NCT04126811] | Phase 2 | 120 participants (Anticipated) | Interventional | 2019-06-01 | Recruiting |
| Evaluation of Fosaprepitant's Effect on Drug Metabolism in Sarcoma Patients Receiving Ifosfamide-based Multi-day Chemotherapy Regimen [NCT01490060] | | 47 participants (Actual) | Interventional | 2012-05-31 | Completed |
| Phase I Study of Romidepsin (ISTODAX®) Plus ICE for Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma [NCT01590732] | Phase 1 | 22 participants (Actual) | Interventional | 2012-10-29 | Completed |
| Phase III Study on Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma. [NCT02063022] | Phase 3 | 278 participants (Actual) | Interventional | 2009-01-22 | Completed |
| Treatment Regimen or Children or Adolescent With Mature B-cell NHL or B-AL in China [NCT02405676] | Phase 2/Phase 3 | 200 participants (Anticipated) | Interventional | 2015-01-31 | Active, not recruiting |
| Phase III Trial Investigating the Potential Benefit of Intensified Peri-operative Chemotherapy With in High-risk CINSARC Patients With Resectable Soft-tissue SARComas [NCT03805022] | Phase 3 | 351 participants (Anticipated) | Interventional | 2019-02-14 | Recruiting |
| B-cell Mature Non-Hodgkin's Lymphoma Treatment Protocol in Children and Adolescents 2021 (B-NHL-M-2021) [NCT05518383] | Phase 4 | 300 participants (Anticipated) | Interventional | 2022-05-25 | Recruiting |
| A Phase II Trial of Tafasitamab and Lenalidomide Followed by Tafasitamab and ICE as Salvage Therapy for Transplant Eligible Patients With Relapsed/ Refractory Large B-Cell Lymphoma [NCT05821088] | Phase 2 | 37 participants (Anticipated) | Interventional | 2023-06-29 | Recruiting |
| The Effect of Antiangiogenic Therapy With Pazopanib Prior to Preoperative Chemotherapy for Subjects With Extremity Soft Tissue Sarcomas: A Randomized Study to Evaluate Response by Imaging [NCT01446809] | | 23 participants (Actual) | Interventional | 2012-04-30 | Completed |
| Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT) [NCT01602666] | Phase 2 | 262 participants (Actual) | Interventional | 2012-05-29 | Active, not recruiting |
| A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-operative Chemotherapy [NCT00134030] | Phase 3 | 1,334 participants (Actual) | Interventional | 2005-11-14 | Completed |
| Multicenter Single Arm Phase II Study of Single Agent Palifosfamide in Recurrent and Incurable Germ Cell Tumors [NCT01808534] | Phase 2 | 5 participants (Actual) | Interventional | 2013-02-28 | Terminated(stopped due to Due to Low Accrual) |
| A Phase I/II Trial of Brentuximab Vedotin (BV), Ifosfamide (I), Carboplatin (C), and Etoposide (E) for Patients With Relapsed or Refractory Hodgkin Lymphoma (BV-ICE) [NCT02227199] | Phase 1/Phase 2 | 45 participants (Actual) | Interventional | 2014-10-10 | Active, not recruiting |
| LS1781: Phase 2 Trial of High Dose Intravenous Ascorbic Acid as an Adjunct to Salvage Chemotherapy in Relapsed / Refractory Lymphoma and Patients With Clonal Cytopenia of Undetermined Significance [NCT03418038] | Phase 2 | 55 participants (Anticipated) | Interventional | 2018-03-23 | Recruiting |
| A Pilot Phase II Study of Pre-Operative Radiation Therapy and Thalidomide (IND 48832; NSC 66847) for Low Grade Primary Soft Tissue Sarcoma or Pre-Operative MAID/Thalidomide/Radiation Therapy for High/Intermediate Grade Primary Soft Tissue Sarcoma of the E [NCT00089544] | Phase 2 | 23 participants (Actual) | Interventional | 2004-06-17 | Terminated |
| Phase I/II, Open-Label Study of R-ICE (Rituximab-Ifosfamide-Carboplatin-Etoposide) With Lenalidomide (R2-ICE) in Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL) [NCT02628405] | Phase 1/Phase 2 | 63 participants (Actual) | Interventional | 2016-05-20 | Active, not recruiting |
| A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Comparing the Efficacy and Safety of a Sintilimab Plus ICE Regimen Versus a Placebo Plus ICE Regimen in Classic Hodgkin's Lymphoma Patients With First-line Standard Chemotherapy [NCT04044222] | Phase 3 | 240 participants (Anticipated) | Interventional | 2019-10-21 | Recruiting |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
| Trial | Outcome |
|---|
| NCT00047320 (6) [back to overview] | Number of Patients Experiencing Toxic Death |
| NCT00047320 (6) [back to overview] | Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity |
| NCT00047320 (6) [back to overview] | Overall Survival (OS) |
| NCT00047320 (6) [back to overview] | Progression-free Survival (PFS) |
| NCT00047320 (6) [back to overview] | The Probability of Event-free Survival (EFS) |
| NCT00047320 (6) [back to overview] | Response to Induction Chemotherapy |
| NCT00072280 (1) [back to overview] | "Failure-free Survival (FFS) in Chemotherapy Plus Possible Surgery Arm" |
| NCT00089544 (1) [back to overview] | Treatment Delivery With Compliance Defined as Receiving at Least 95% of the Pre-operative Protocol Dose of RT, All 3 Cycles of MAID (if Applicable), and Receive Thalidomide on 75% of the Days During Radiation |
| NCT00134030 (3) [back to overview] | Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 |
| NCT00134030 (3) [back to overview] | Percentage of Patients With Overall Survival |
| NCT00134030 (3) [back to overview] | Event-free Survival (EFS) |
| NCT00354744 (3) [back to overview] | Number of Patients With Complete or Partial Response Assessed by RECIST Criteria |
| NCT00354744 (3) [back to overview] | Percentage of Patients Event Free at 4 Years Following Study Entry |
| NCT00354744 (3) [back to overview] | Percentage of Patients Experiencing Adverse Events Due to Concurrent Therapy |
| NCT00467051 (2) [back to overview] | The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity. |
| NCT00467051 (2) [back to overview] | Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria |
| NCT00499343 (1) [back to overview] | CD34+ Cells/kg in Blood Stem Cells |
| NCT00712582 (2) [back to overview] | 2-year PFS From the Start of Induction Therapy Conditional |
| NCT00712582 (2) [back to overview] | Overall Survival at 1 Year |
| NCT00720109 (5) [back to overview] | Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy |
| NCT00720109 (5) [back to overview] | Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events |
| NCT00720109 (5) [back to overview] | Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib) |
| NCT00720109 (5) [back to overview] | Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation |
| NCT00720109 (5) [back to overview] | Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy |
| NCT00742924 (1) [back to overview] | Limiting Toxicity |
| NCT00954174 (7) [back to overview] | Patient-reported Peripheral Neuropathy Symptoms - Post Baseline |
| NCT00954174 (7) [back to overview] | Duration of Progression-free Survival |
| NCT00954174 (7) [back to overview] | Overall Survival |
| NCT00954174 (7) [back to overview] | Patient Reported Peripheral Neuropathy Symptoms - Baseline |
| NCT00954174 (7) [back to overview] | Patient-Reported Quality of Life (QOL) - Baseline |
| NCT00954174 (7) [back to overview] | Incidence of Adverse Events as Assessed by CTCAE Version 3.0 |
| NCT00954174 (7) [back to overview] | Patient Reported Quality of Life (QOL) - Post Baseline |
| NCT00967369 (4) [back to overview] | Overall Response After 3 Cycles of Botezomib Plus ICE (BICE) Versus Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma |
| NCT00967369 (4) [back to overview] | PET Scan Response After 3 Cycles of BICE Versus ICE Chemotherapy. |
| NCT00967369 (4) [back to overview] | Progression Free Survival (PFS) Rate at 12 Months |
| NCT00967369 (4) [back to overview] | Overall Survival (OS) Rate at 24 Months |
| NCT01055314 (5) [back to overview] | Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment |
| NCT01055314 (5) [back to overview] | Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0 |
| NCT01055314 (5) [back to overview] | Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment |
| NCT01055314 (5) [back to overview] | Event-Free Survival |
| NCT01055314 (5) [back to overview] | Response Rate (CR + PR) |
| NCT01097057 (4) [back to overview] | Number of Patients Who Achieved ≥5 x 10^6 CD34 Cells/kg in ≤4 Apheresis Days |
| NCT01097057 (4) [back to overview] | Total Number of Participants Who Did Not Collect ≥5 x 10^6 CD34 Cells/kg in a Maximum of Four Apheresis Days |
| NCT01097057 (4) [back to overview] | Number of Participants Requiring One or Two Apheresis Collection Days to Reach ≥5 x 10^6 CD34 Cells/kg |
| NCT01097057 (4) [back to overview] | Number of Patients to Mobilize ≥5 x 10^6 CD34 Cells/kg Autologous PBSC (Efficacy) |
| NCT01231906 (1) [back to overview] | Event-Free Survival |
| NCT01446809 (7) [back to overview] | Change in Maximum SUV of Tumors Measured by FDG-PET Post Receipt of 2 Courses of Preoperative Chemotherapy |
| NCT01446809 (7) [back to overview] | Change in Levels of VEGF and Soluble VEGFR2 Assessed by ELISA on Plasma and Tumor Extracts |
| NCT01446809 (7) [back to overview] | Progression Free Survival |
| NCT01446809 (7) [back to overview] | Pharmacokinetic Profile of Pazopanib |
| NCT01446809 (7) [back to overview] | Overall Survival |
| NCT01446809 (7) [back to overview] | Number of Participants With Pathologic Response at the Time of Surgery as Measured by % Tumor Viability ( >= 95% Necrosis) |
| NCT01446809 (7) [back to overview] | Change in Maximum SUV of Tumors Measured by FDG-PET Pre- and Post Receipt of Pazopanib Versus Placebo |
| NCT01490060 (1) [back to overview] | Complete Response |
| NCT01602666 (6) [back to overview] | Estimation of the Overall Survival (OS) Distribution of Patients With NGGCT Treated With IFR Assessed |
| NCT01602666 (6) [back to overview] | Estimation of the PFS Distribution of Patients With NGGCT Treated With Involved-field Radiation Therapy (IFR) |
| NCT01602666 (6) [back to overview] | Estimation of the PFS Distribution of Patients With Localized Germinoma Patients and Cerebrospinal Fluid (CSF) Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL |
| NCT01602666 (6) [back to overview] | Estimation of the OS Distribution of Patients With Localized Germinoma Patients and CSF Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL |
| NCT01602666 (6) [back to overview] | 3-year Progression-free Survival (PFS) Rate of Patients With Nongerminomatous Germ Cell Tumor (NGGCT) Who Were Treated With Reduced Dose Whole Ventricular-field Irradiation |
| NCT01602666 (6) [back to overview] | 3-year PFS Rate of Patients With Localized CNS Germinoma Who Were Treated With Reduced Dose Radiation Therapy |
| NCT01808534 (5) [back to overview] | Treatment Related Adverse Events Grade 3 or Higher |
| NCT01808534 (5) [back to overview] | Duration of Remission in Patients Who Achieve a Partial or Complete Response |
| NCT01808534 (5) [back to overview] | Overall Response Rate (Defined as Partial Response or Complete Response) |
| NCT01808534 (5) [back to overview] | Overall Survival |
| NCT01808534 (5) [back to overview] | Progression Free Survival (PFS) |
| NCT01959698 (6) [back to overview] | Progression-free Survival |
| NCT01959698 (6) [back to overview] | Overall Survival |
| NCT01959698 (6) [back to overview] | Overall Response Rate (PR + CR) |
| NCT01959698 (6) [back to overview] | MTD Defined as the Dose of Carfilzomib Added to Standard R-ICE Chemotherapy Which, if Exceeded, Would Put the Patient at an Undesirable Risk of Medically Unacceptable Dose-limiting Toxicities (Phase I) |
| NCT01959698 (6) [back to overview] | Complete Response Rate According to the International Working Group Response Criteria as Reported by the Revised Cheson Criteria |
| NCT01959698 (6) [back to overview] | Toxicity of the Addition of Carfilzomib to R-ICE at the MTD, Assessed by the CTEP Version 4.0 of the NCI CTCAE |
| NCT01979536 (3) [back to overview] | Prognostic Significance of Minimal Residual Disease |
| NCT01979536 (3) [back to overview] | Occurrence of Grade 3+ Non-hematologic Adverse Events |
| NCT01979536 (3) [back to overview] | Event Free Survival (EFS) |
| NCT02050919 (7) [back to overview] | Distant Disease-free Survival (Stage IIB-III Patients) |
| NCT02050919 (7) [back to overview] | Number of Participants With Wound Complications |
| NCT02050919 (7) [back to overview] | Overall Disease-free Survival (Stage IIB-III Patients) |
| NCT02050919 (7) [back to overview] | Overall Survival at 2 Years |
| NCT02050919 (7) [back to overview] | Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis. |
| NCT02050919 (7) [back to overview] | Number of Participants With Local Recurrence |
| NCT02050919 (7) [back to overview] | Number of Grade 3-4 Adverse Events |
| NCT02112916 (6) [back to overview] | EFS for Very High Risk (VHR) T-ALL Patients Treated With High Risk (HR) Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Become Minimal Residual Disease (MRD) Negative and Those Who Remain MRD Positive at the End of HR Block 3 |
| NCT02112916 (6) [back to overview] | EFS for Very High Risk (VHR) T-LLy Patients Treated With HR Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Have Complete or Partial Remission and Those Who do Not Respond |
| NCT02112916 (6) [back to overview] | Event-free Survival (EFS) for Modified Augmented Berlin-Frankfurt-Munster Backbone With or Without Bortezomib in All Randomized Patients |
| NCT02112916 (6) [back to overview] | Toxicity Rates Associated With Modified Standard Therapy, Including Dexamethasone and Additional Pegaspargase |
| NCT02112916 (6) [back to overview] | Cumulative Incidence Rates of Isolated Central Nervous System (CNS) Relapse for SR and IR T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no CRT) and Similar Patients on AALL0434 (Receive CRT) |
| NCT02112916 (6) [back to overview] | EFS for Standard (SR) and Intermediate Risk (IR) T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no Cranial Radiation Therapy [CRT]) and Similar Patients on AALL0434 (Received CRT) |
| NCT02180867 (6) [back to overview] | Feasible Dose: Pediatric |
| NCT02180867 (6) [back to overview] | Feasible Dose: Adult |
| NCT02180867 (6) [back to overview] | Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10 |
| NCT02180867 (6) [back to overview] | Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) |
| NCT02180867 (6) [back to overview] | Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) |
| NCT02180867 (6) [back to overview] | Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13 |
| NCT02227199 (4) [back to overview] | 2 Year Overall Survival |
| NCT02227199 (4) [back to overview] | 2 Year Progression-free Survival |
| NCT02227199 (4) [back to overview] | Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy |
| NCT02227199 (4) [back to overview] | Percentage of Patients That Achieve a Complete Remission Following Study Treatment |
| NCT02306161 (3) [back to overview] | Overall Survival |
| NCT02306161 (3) [back to overview] | Frequency of Toxicity-events |
| NCT02306161 (3) [back to overview] | Event-free Survival |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib |
| NCT02432274 (23) [back to overview] | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level |
| NCT02432274 (23) [back to overview] | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR) |
| NCT02432274 (23) [back to overview] | Cohort 3A: Recommended Dose (RD) of Lenvatinib When Given in Combination With Etoposide and Ifosfamide |
| NCT02432274 (23) [back to overview] | Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR) |
| NCT02432274 (23) [back to overview] | Cohort 1: Recommended Dose (RD) of Lenvatinib |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) |
| NCT02432274 (23) [back to overview] | Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4 |
| NCT02432274 (23) [back to overview] | Cohort 2A: Number of Participants With Best Overall Response (BOR) |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score |
| NCT02432274 (23) [back to overview] | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control |
| NCT02732015 (1) [back to overview] | Number of Participants With Complete Response (CR) of Rolapitant Hydrochloride Administered as a Single-dose |
Number of Patients Experiencing Toxic Death
Toxic death, defined as death predominantly attributable to treatment-related causes. (NCT00047320)
Timeframe: During chemotherapy (up to 18 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Radiation Therapy (CR From Induction) | 0 |
Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity
The number of patients who experienced non-hematological grade 4 toxicities anytime during chemotherapy. (NCT00047320)
Timeframe: During chemotherapy(up to 18 weeks)
| Intervention | participants (Number) |
|---|
| Radiation Therapy (CR From Induction) | 22 |
Overall Survival (OS)
Overall Survival was defined as time from study entry to death from any cause. Overall survival was estimated by KM estimate. (NCT00047320)
Timeframe: At 3 years from study entry
| Intervention | Probability (Number) |
|---|
| Radiation Therapy (CR From Induction) | 0.927 |
Progression-free Survival (PFS)
Progression-free Survival was defined as time from study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms are censored in this analysis. Progression -free survival was estimated by KM estimate. (NCT00047320)
Timeframe: At 3 years from study entry
| Intervention | Probability (Number) |
|---|
| Radiation Therapy (CR From Induction) | 0.837 |
The Probability of Event-free Survival (EFS)
Event-free Survival was defined as time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. Event-free survival was estimated by KM estimate. (NCT00047320)
Timeframe: At 3 years from study entry
| Intervention | Probability (Number) |
|---|
| Radiation Therapy (CR From Induction) | 0.837 |
Response to Induction Chemotherapy
A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response. (NCT00047320)
Timeframe: 18 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Responder | Non-Responder |
|---|
| Radiation Therapy (CR From Induction) | 74 | 11 |
"Failure-free Survival (FFS) in Chemotherapy Plus Possible Surgery Arm"
Failure is defined as the occurrence of one of the following: disease progression, defined as at least a 20% increase in the disease measurement, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions; relapse (defined with same criteria as for disease progression) after response; or death as a first event. Data will be summarized as number of eligible patients in each of the following categories at the time of data cutoff for analyses of 5-year FFS: 1)Failed; 2)Failure-free through 5 years of follow-up; 3)Failure-free until data cutoff (if less than 5 years of follow-up); 4)Withdrew from study; 5)Lost to follow-up. NOTE: Reported data are through March 2008 (see Caveats section). (NCT00072280)
Timeframe: Study enrollment until failure, completion of follow-up, or completion of 5-year FFS analyses (up to 5 years)
| Intervention | participants (Number) |
|---|
| Failed | Failure-free through 5 years of follow-up | Failure-free at cutoff (if < 5 years follow-up) | Withdrew from study | Lost to follow-up |
|---|
| Chemotherapy Plus Possible Surgery | 1 | 0 | 1 | 0 | 0 |
Treatment Delivery With Compliance Defined as Receiving at Least 95% of the Pre-operative Protocol Dose of RT, All 3 Cycles of MAID (if Applicable), and Receive Thalidomide on 75% of the Days During Radiation
Was to be estimated using a binomial distribution and accompanied by the associated 95% confidence interval. Due to early study closure, this endpoint could not be fully evaluated per the protocol plan. (NCT00089544)
Timeframe: Duration of treatment (which can continue up to approximately 15 months).
| Intervention | participants (Number) |
|---|
| Not Compliant | Compliant |
|---|
| Cohort A (Chemotherapy, Radiation, Thalidomide, Surgery) | 5 | 10 |
,| Cohort B (Thalidomide, Radiation, Surgery) | 2 | 5 |
Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Percentages of patients experiencing grade 3 and 4 adverse events. These will be compared using chi-square tests or Fisher's exact tests where appropriate. (NCT00134030)
Timeframe: Adverse events are assessed for up to 10 years per participant.
| Intervention | Participants (Count of Participants) |
|---|
| MAP-GR | 348 |
| MAPifn | 340 |
| MAP-PR | 287 |
| MAPIE | 281 |
Percentage of Patients With Overall Survival
"Overall survival is time from randomization until death from any cause.~Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Participants will be assessed for up to 10 years. 5 year overall survival is provided as a summary." (NCT00134030)
Timeframe: From date of randomization to date of death.
| Intervention | Percentage of participants (Number) |
|---|
| MAP-GR | 84 |
| MAPifn | 84 |
| MAP-PR | 68 |
| MAPIE | 68 |
Event-free Survival (EFS)
"EFS is defined as time from randomisation to the first of: death, detection of local recurrence or metastasis, progression of metastatic disease, or detection of a secondary malignancy.~EFS will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Follow up per participant will be assessed for up to 10 years. The 3 year EFS is provided as a summary." (NCT00134030)
Timeframe: From date of randomization to date of the event.
| Intervention | Percentage EFS (Number) |
|---|
| MAP-GR | 74 |
| MAPifn | 77 |
| MAP-PR | 55 |
| MAPIE | 53 |
Number of Patients With Complete or Partial Response Assessed by RECIST Criteria
"Volumetric measurements of the primary tumor using an elliptical model (0.5 x the product of the 3 largest perpendicular diameters) to assess response to neoadjuvant therapy. The RECIST (Response Evaluation Criteria in Solid Tumors) from the NCI will be used for assessment of the size of measurable metastases, including nodal metastases. Primary Tumor Measurement: Technical guidelines for cross-sectional imaging computed tomography (CT) slice thickness should be 5mm or less and the diameter of the measurable mass should be at least twice the reconstructed slice thickness. Smaller masses are considered detectable, but will be counted as non-measurable. Complete Response (CR): Complete disappearance of the tumor confirmed at >4 weeks. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment. Progressive Disease (PD): At least 40% increase in tumor volume compared to the smallest volume obtained since the beginning." (NCT00354744)
Timeframe: Protocol week 6 evaluation
| Intervention | percentage of participants (Number) |
|---|
| High_Risk_Rhabdomyosarcoma | 63 |
Percentage of Patients Event Free at 4 Years Following Study Entry
Event-free survival: Time to recurrence, second malignancy, or death as a first event, estimated from a Kaplan Meier curve (NCT00354744)
Timeframe: 4 years
| Intervention | Percentage of patients (Number) |
|---|
| High_Risk_Rhabdomyosarcoma | 36 |
Percentage of Patients Experiencing Adverse Events Due to Concurrent Therapy
Adverse events are reported for patients receiving concurrent irinotecan hydrochloride and radiotherapy. (NCT00354744)
Timeframe: From enrollment to up to 2 years
| Intervention | percentage of patients (Number) |
|---|
| Course 1 | Course 2 | Course 3 | Course 4 |
|---|
| High_Risk_Rhabdomyosarcoma | 53.3 | 68.4 | 79.3 | 55.7 |
The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.
(NCT00467051)
Timeframe: Two cycles of chemotherapy; expected to be 42 days of treatment.
| Intervention | Participants (Count of Participants) |
|---|
| Experimental | 18 |
Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Patients who demonstrate a PR or CR, as defined below, will be considered as responders. RECIST criteria: CR (complete response) = disappearance of all target lesions, PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD (stable disease) = small changes that do not meet above criteria. (NCT00467051)
Timeframe: At baseline (day 1) and after completion of protocol therapy (2 cycles or 42 days)
| Intervention | participants (Number) |
|---|
| Responder | Non-Responder |
|---|
| Treatment (Chemotherapy, Biological Therapy) | 12 | 8 |
CD34+ Cells/kg in Blood Stem Cells
After blood counts return to normal, stem cell collection (takes approximately 4 hours) up to 6 sessions. (NCT00499343)
Timeframe: The process of stem cell collections take about 4 hours, 1-6 sessions may be needed.
| Intervention | CD34+ cells/kg (Median) |
|---|
| Rituximab + Ifosfamide + Etoposide + 2 Growth Factors | 7.5 |
| Rituximab + Ifosfamide + Etoposide + 1 Growth Factor | 10.34 |
2-year PFS From the Start of Induction Therapy Conditional
2-year PFS from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation. (NCT00712582)
Timeframe: 2 years
| Intervention | percentage of patients (Number) |
|---|
| Consolidation A | 86.6 |
| Consolidation B | 90.6 |
| Consolidation C | 0.4 |
Overall Survival at 1 Year
Overall survival from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation. (NCT00712582)
Timeframe: 1 year
| Intervention | Percent of patients (Number) |
|---|
| Consolidation A | 98.3 |
| Consolidation B | 96.9 |
| Consolidation C | 50.0 |
Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy
Event-Free Survival (EFS) curves will be constructed using the Kaplan-Meier life table method with standard errors computed using the method of Peto and Peto. A 1-sided 95% confidence interval for EFS will be constructed. (NCT00720109)
Timeframe: At 3 years
| Intervention | Percent probability (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 79.8 |
| Standard-risk | 83.2 |
| High-risk | 66.7 |
Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events
Number of patients in safety cohort with dose limiting toxicity (DLT)(including treatment delay) (NCT00720109)
Timeframe: Weeks 3 through 23 of treatment (From week 3 Induction through Intensification Block 1)
| Intervention | Pts with DLTs (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 1 |
Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib)
An event is defined as: Induction failure, relapse at any site, secondary malignancy, or death. (NCT00720109)
Timeframe: From the time entry on study to first event or date of last follow-up, assessed up to 7 years
| Intervention | percentage of patients (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 79.8 |
| Standard-risk | 83.2 |
| High-risk | 66.7 |
Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation
A 1-sample Z-test of proportions (alpha=5%, 1-sided test) will be used. (NCT00720109)
Timeframe: At end of consolidation (at 11 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 10.5 |
| Standard-risk | 0 |
| High-risk | 66.7 |
Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy
Percent of patients MRD Positive (MRD > 0.01%) at End of Induction. (NCT00720109)
Timeframe: At the end of induction therapy (at 5 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 40.7 |
| Standard-risk | 29.2 |
| High-risk | 100.0 |
Limiting Toxicity
"The occurrence of Limiting Toxicity defined as Any CTC AE version 4 Grade 3 and 4 non-hematologic toxicity thought to be possibly, probably or definitely related to zoledronic acid with the specific exclusion of:~Grade 3 nausea and vomiting controlled with adequate antiemetic prophylaxis.~Grade 3 transaminase (AST/ALT) that occurs during the evaluation period but resolves to ≤ Grade 2, before the planned dose of therapy after definitive surgery.~Grade 3 fever or infection.~Grade 3 or 4 hypocalcemia (see Section 5.1.1)~Grade 3 mucositis.~Grade 3 fatigue that returns to ≤ Grade 2, before the planned dose of therapy after definitive surgery.~Grade 3 joint range of motion, decreased or joint effusion that is related to the primary tumor." (NCT00742924)
Timeframe: Enrollment through the first 12 weeks of therapy.
| Intervention | participants (Number) |
|---|
| Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid | 1 |
| Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid | 1 |
| Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid | 3 |
| Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD | 2 |
Patient-reported Peripheral Neuropathy Symptoms - Post Baseline
Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 11 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). The Ntx score ranges 0-44 with a large score suggesting less peripheral neuropathy symptoms.Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life. (NCT00954174)
Timeframe: Prior to cycle 3, Prior to cycle 6, 30 weeks post cycle 1
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Prior to cycle 3 | Prior to cycle 6 | 30 weeks post cycle 1 |
|---|
| Regimen I - Uterine and Non-Uterine Subjects | 37.2 | 34.1 | 34.8 |
,| Regimen II - Uterine and Non-Uterine Subjects | 37.0 | 34.2 | 34.9 |
Duration of Progression-free Survival
Measured in months from randomization to last contact or the earlier of the date of progression or death. (NCT00954174)
Timeframe: Approximately 9 years and 7 months
| Intervention | months (Median) |
|---|
| Regimen I - Uterine Carcinsarcoma Subjects | 16.3 |
| Regimen II - Uterine Carcinsarcoma Subjects | 11.7 |
| Regimen III - Non-uterine Carcinsarcoma Subjects | 14.6 |
| Regimen IV - Non-uterine Carcinsarcoma Subjects | 10.3 |
Overall Survival
Measured in months from randomization to last contact or death. Primary analysis was restricted to the eligible uterine carcinosarcoma cohort. (NCT00954174)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 115 months.
| Intervention | months (Median) |
|---|
| Regimen I- Uterine Carcinsarcoma Subjects | 37.3 |
| Regimen II - Uterine Carcinsarcoma Subjects | 29 |
Patient Reported Peripheral Neuropathy Symptoms - Baseline
Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 11 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). . The Ntx score ranges 0-44 with a large score suggesting less peripheral neuropathy symptoms. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life. (NCT00954174)
Timeframe: Baseline (Pre cycle 1)
| Intervention | units on a scale-baseline (Mean) |
|---|
| Regimen I - Uterine and Non-Uterine Subjects | 40.2 |
| Regimen II - Uterine and Non-Uterine Subjects | 41.0 |
Patient-Reported Quality of Life (QOL) - Baseline
Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). The FACT-En TOI is a scale for assessing general QOL of endometrial cancer patients. The FACT-En TOI score ranges 0-120 with a large score suggesting better QOL. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life. (NCT00954174)
Timeframe: Baseline - Prior to study treatment
| Intervention | units on a scale (time point) (Mean) |
|---|
| Regimen I - Uterine and Non-Uterine Subjects | 96.2 |
| Regimen II - Uterine and Non-Uterine Subjects | 97.5 |
Incidence of Adverse Events as Assessed by CTCAE Version 3.0
Maximum grade experienced among all treated and eligible patients. The grades are described by severity. Grade 1 is the lowest (most mild) and Grade 5 being death (most severe). Adverse events were analyzed across cohorts since disease site was considered independent of AEs. (NCT00954174)
Timeframe: Patients were assessed for adverse events during active protocol treatment and up to 30 days after the last cycle of treatment on the protocol.
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Regimen I - Uterine and Non-Uterine Subjects | 3 | 22 | 107 | 130 | 6 |
,| Regimen II - All Uterine and Non-Uterine Subjects | 3 | 80 | 97 | 61 | 3 |
Patient Reported Quality of Life (QOL) - Post Baseline
Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). The FACT-En TOI is a scale for assessing general QOL of endometrial cancer patients. The FACT-En TOI score ranges 0-120 with a large score suggesting better QOL. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life. (NCT00954174)
Timeframe: Prior to cycle 3, Prior to cycle 6, 30 weeks post cycle 1.
| Intervention | units on a scale (time point) (Least Squares Mean) |
|---|
| Pre-cycle 3 | Pree-cycle 6 | 30 weeks post cycle 1 |
|---|
| Regimen I - Uterine and Non-Uterine Subjects | 93.3 | 91.6 | 98.0 |
,| Regimen II - Uterine and Non-Uterine Subjects | 93.3 | 91.6 | 97.6 |
Overall Response After 3 Cycles of Botezomib Plus ICE (BICE) Versus Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
Response rates for Bortezomib, Ifosfamide, Carboplatin, Etoposide (BICE) and Ifosfamide, Carboplatin, Etoposide (ICE) treatment groups were assessed by the 1999 International Working Group (IWG)(CT alone) (Cheson et al., 1999) and compared to 2007 IWG (CT plus PET) (Cheson et al., 2007) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT00967369)
Timeframe: From baseline to 3 cycles of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Overall Response | Complete Response (CR) | Partial Response (PR) | Progressive Disease (PD) | Stable Disease (SD) |
|---|
| BICE (Bortezomib, Ifosfamide, Carboplatin, Etoposide) | 7 | 3 | 4 | 0 | 1 |
,| ICE (Ifosfamide, Carboplatin, Etoposide) | 6 | 1 | 5 | 0 | 3 |
PET Scan Response After 3 Cycles of BICE Versus ICE Chemotherapy.
Response rates for BICE and ICE treatment groups will be assessed by 1999 IWG (CT alone) (Cheson et al., 1999) and compared to 2007 IWG (CT plus PET) (Cheson et al., 2007) criteria. (NCT00967369)
Timeframe: Baseline up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| PET negativity : Complete Response (CR) | PET negativity : Partial Response (PR) | PET negativity : Stable Disease (SD) | PET positivity : Partial Response (PR) | PET positivity : Stable Disease (SD) | PET positivity : Progressive Disease (PD) |
|---|
| BICE (Bortezomib, Ifosfamide, Carboplatin, Etoposide) | 3 | 0 | 0 | 4 | 1 | 2 |
,| ICE (Ifosfamide, Carboplatin, Etoposide) | 6 | 4 | 1 | 2 | 2 | 0 |
Progression Free Survival (PFS) Rate at 12 Months
Progression free survival time is defined as the time interval from treatment start to progression or death due to any cause whichever happens first. Participants will be censored at the last follow-up date, if an event(progression/death) is not observed during the follow-up. (NCT00967369)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
| Intervention | percentage of participants (Number) |
|---|
| BICE (Bortezomib, Ifosfamide, Carboplatin, Etoposide) | 50 |
| ICE (Ifosfamide, Carboplatin, Etoposide) | 70 |
Overall Survival (OS) Rate at 24 Months
Overall Survival is time from date of treatment start until date of death due to any cause or last Follow-up within 24 months. (NCT00967369)
Timeframe: 24 months
| Intervention | percentage of participants (Number) |
|---|
| BICE (Bortezomib, Ifosfamide, Carboplatin, Etoposide) | 70 |
| ICE (Ifosfamide, Carboplatin, Etoposide) | 89 |
Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment
Proportion of no Grade 3+ cardiac toxicity. (NCT01055314)
Timeframe: From start to week 26 of therapy
| Intervention | Proportion of Participants (Number) |
|---|
| IMC-A12 | 0.9390 |
Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Number of patients with grade 3+ adverse events (AE) during therapy. (Grade 3+) = (Grade 3 + Grade 4 + Grade 5) . Grade 3: Severe and undesirable AE; Grade 4: Life threatening or disabling AE; Grade 5: Death related to AE. (NCT01055314)
Timeframe: Up to 54 weeks
| Intervention | Participants (Number) |
|---|
| IMC-A12 | 89 |
| Temozolomide | 61 |
Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment
Proportion of no Grade 4+ non-hematologic toxicity. (NCT01055314)
Timeframe: From start to week 26 of therapy
| Intervention | Proportion of Participants (Number) |
|---|
| Temozolomide | 0.7097 |
Event-Free Survival
Probability of no relapse, secondary malignancy, or death after 3 years in the study. (NCT01055314)
Timeframe: 3 years
| Intervention | Probability (Number) |
|---|
| IMC-A12 | 0.1627 |
| Temozolomide | 0.1919 |
Response Rate (CR + PR)
Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at > 4 weeks. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment; Overall Response (OR) = CR + PR. (NCT01055314)
Timeframe: From the start of treatment until a maximum of 2 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities
| Intervention | Proportion of Participants (Number) |
|---|
| IMC-A12 | 0.7667 |
| Temozolomide | 0.7846 |
Number of Patients Who Achieved ≥5 x 10^6 CD34 Cells/kg in ≤4 Apheresis Days
Number of patients to collect at least 5 x 10^6 CD34 cells/kg in under 4 apheresis procedures. (NCT01097057)
Timeframe: Up to Four Apheresis Days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide) | 17 |
Total Number of Participants Who Did Not Collect ≥5 x 10^6 CD34 Cells/kg in a Maximum of Four Apheresis Days
Number of participants who did not collect ≥5 x 10^6 CD34 cells/kg in up to four apheresis days (NCT01097057)
Timeframe: Up to Four Apheresis Days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide) | 0 |
Number of Participants Requiring One or Two Apheresis Collection Days to Reach ≥5 x 10^6 CD34 Cells/kg
Number of participants requiring one or two apheresis collection days to reach collection goal. (NCT01097057)
Timeframe: Up to Four Apheresis Days
| Intervention | Participants (Count of Participants) |
|---|
| One apheresis collection day | Two apheresis collection days | Three apheresis collection days | Four apheresis collection days |
|---|
| Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide) | 15 | 2 | 0 | 0 |
Number of Patients to Mobilize ≥5 x 10^6 CD34 Cells/kg Autologous PBSC (Efficacy)
Number of patients who achieved ≥5 x 10^6 CD34 cells/kg autologous PBSC collection by apheresis. (NCT01097057)
Timeframe: One Month
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide) | 17 |
Event-Free Survival
Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact. (NCT01231906)
Timeframe: 5 years after enrollment
| Intervention | Percent Probability (Number) |
|---|
| Arm A (Combination Chemotherapy) | 77.64 |
| Arm B (Combination Chemotherapy, Topotecan Hydrochloride) | 78.79 |
Change in Maximum SUV of Tumors Measured by FDG-PET Post Receipt of 2 Courses of Preoperative Chemotherapy
Change in maximum SUV of tumors measured by FDG-PET. Comparison conducted using a two-sided Wilcoxon rank sum test. (NCT01446809)
Timeframe: From baseline to 8 weeks
| Intervention | SUV (Median) |
|---|
| Pazopanib | -1.1 |
| Placebo | -4.0 |
Change in Levels of VEGF and Soluble VEGFR2 Assessed by ELISA on Plasma and Tumor Extracts
Plasma will be collected for measurement of VEGF and soluble VEGFR2 (sVEGFR2) at baseline, after the 14 day Run-in period of pazopanib, after completion of neoadjuvant chemotherapy and approximately every 3 months thereafter until completion of pazopanib maintenance therapy, when indicated. Quantitative enzyme-linked immunosorbent assays (ELISA) for VEGF and sVEGFR2 will be performed on plasma and tumor extracts. Plasma will also be collected for micro RNA at baseline, after the 14 day Run-in period of pazopanib, following neoadjuvant chemotherapy and every 3 months thereafter until completion of pazopanib maintenance therapy, when indicated. (NCT01446809)
Timeframe: At baseline and after 14 days
| Intervention | percentage of concentration (Number) |
|---|
| Pazopanib | NA |
| Placebo | NA |
Progression Free Survival
Defined as the duration of time from randomization to progressive disease (per RECIST), local recurrence, distant metastatic disease (exclusive of stage IV subjects), or death, whichever occurs first. (NCT01446809)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Pazopanib Hydrochloride) | 10 |
| Arm II (Placebo) | 4 |
Pharmacokinetic Profile of Pazopanib
Trough plasma pazopanib concentration measured during the 14 day run-in period on days 10 through 14. (NCT01446809)
Timeframe: Up to 14 days
| Intervention | ng/mL (Mean) |
|---|
| Pazopanib | 56.38 |
| Placebo | 0 |
Overall Survival
Defined as the interval of time from randomization until death from any cause. (NCT01446809)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Pazopanib | 12 |
| Placebo | 4 |
Number of Participants With Pathologic Response at the Time of Surgery as Measured by % Tumor Viability ( >= 95% Necrosis)
Estimate the amount of viable tumor, and report the percentage of necrosis. Analysis was only completed on a subset of participants. (NCT01446809)
Timeframe: An expected average of 12 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Pazopanib | 6 |
| Placebo | 6 |
Change in Maximum SUV of Tumors Measured by FDG-PET Pre- and Post Receipt of Pazopanib Versus Placebo
Change in maximum SUV (standardized uptake value) of tumors measured by FDG-PET. Comparison conducted using a two-sided Wilcoxon rank sum test. (NCT01446809)
Timeframe: From baseline to 15 days
| Intervention | Standardized uptake value-SUV (Median) |
|---|
| Pazopanib | -0.1 |
| Placebo | -0.1 |
Complete Response
Complete response (CR) defined as: No emetic episodes and no rescue medications. This is a cross-over designed study, the outcomes by single dose, two doses and control cycles were evaluated by combining the results from both cycle 1 and cycle 2 according to the treatment received. (NCT01490060)
Timeframe: From Day 1 to Day 5 in two 21-days cycles (Cycle 1 and Cycle 2).
| Intervention | percentage of participants (Number) |
|---|
| Control Cycle (Arm A/Arm B) | 17 |
| Arm A: Single Dose, Day 1 | 10 |
| Arm B: Two Doses, Day 1 + Day 4 | 50 |
Estimation of the Overall Survival (OS) Distribution of Patients With NGGCT Treated With IFR Assessed
Kaplan Meier estimate of the 3-year overall survival (OS) is provided. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. (NCT01602666)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT) | 92.42 |
Estimation of the PFS Distribution of Patients With NGGCT Treated With Involved-field Radiation Therapy (IFR)
Kaplan Meier estimate of the 3-year PFS is provided. PFS is the time interval measured from enrollment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study. (NCT01602666)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT) | 87.88 |
Estimation of the PFS Distribution of Patients With Localized Germinoma Patients and Cerebrospinal Fluid (CSF) Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL
Kaplan Meier estimate of the 3-year PFS rate is provided. PFS is the time interval measured from initiation of treatment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study. (NCT01602666)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| hCGbeta <= 50 mIU/mL | 93.26 |
| 50 mIU/mL < hCGbeta <= 100 mIU/mL | 80.00 |
Estimation of the OS Distribution of Patients With Localized Germinoma Patients and CSF Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL
Kaplan Meier estimate of the 3-year overall survival (OS) is provided for each group. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. (NCT01602666)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| hCGbeta <= 50 mIU/mL | 98.38 |
| 50 mIU/mL < hCGbeta <= 100 mIU/mL | 100 |
3-year Progression-free Survival (PFS) Rate of Patients With Nongerminomatous Germ Cell Tumor (NGGCT) Who Were Treated With Reduced Dose Whole Ventricular-field Irradiation
"Binomial estimate of the 3-year PFS rate defined as Yes for patients who were followed up per protocol and were progression free at 3-years, and No for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from enrollment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study." (NCT01602666)
Timeframe: 3 years
| Intervention | percentage of patients (Number) |
|---|
| Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT) | 83.33 |
3-year PFS Rate of Patients With Localized CNS Germinoma Who Were Treated With Reduced Dose Radiation Therapy
"Binomial estimate of the 3-year PFS rate defined as Yes for patients who were followed up per protocol and were progression free at 3-years, and No for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from initiation of treatment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study." (NCT01602666)
Timeframe: 3 years
| Intervention | percentage of patients (Number) |
|---|
| Stratum 2 Localized Germinoma | 86.49 |
Duration of Remission in Patients Who Achieve a Partial or Complete Response
The duration of remission is from the time of confirmed partial or complete response until progression or death. Patients continuing in remission at the end of the study will be treated as censored. Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Note: There were no patients who achieved partial or complete response. (NCT01808534)
Timeframe: Up to 2 years
| Intervention | months (Median) |
|---|
| Treatment (Palifosfamide) | 0 |
Overall Response Rate (Defined as Partial Response or Complete Response)
The percent of patients who were shown as having a partial remission or better based on definitions of response in RECIST 1.1. At least a 30% decrease in the sum of the diameters of target lesions, in reference to baseline sum diameters, needs to be confirmed to be considered as partial response or better. Note: There were no patients with a partial or complete response. (NCT01808534)
Timeframe: Up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Palifosfamide) | 0 |
Overall Survival
Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Time until death or last evaluation will be calculated. If a patient did not die, they will be censored in the analysis at their last known alive date. (NCT01808534)
Timeframe: Up to 2 years
| Intervention | months (Median) |
|---|
| Treatment (Palifosfamide) | 0.95 |
Progression Free Survival (PFS)
Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Time until progression, death or last evaluation will be calculated. If a patient did not progress or die, they will be censored at their last evaluation in the analysis. (NCT01808534)
Timeframe: Up to 2 years
| Intervention | months (Median) |
|---|
| Treatment (Palifosfamide) | 0.69 |
Progression-free Survival
The estimated distributions of progression-free survival will be obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. It is assumed a priori that any drop out times will be non-informative in terms of the censoring mechanism. Groups defined by levels of categorical or dichotomized numeric demographic/baseline variables will be compared in regards to time-to-event distributions using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses. (NCT01959698)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| Treatment (Carfilzomib, Rituximab, Chemotherapy) | 15.2 |
Overall Survival
The estimated distributions of overall survival will be obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. It is assumed a priori that any drop out times will be non-informative in terms of the censoring mechanism. Groups defined by levels of categorical or dichotomized numeric demographic/baseline variables will be compared in regards to time-to-event distributions using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses. (NCT01959698)
Timeframe: From the start of treatment until death for any reason, assessed up to 5 years
| Intervention | months (Median) |
|---|
| Treatment (Carfilzomib, Rituximab, Chemotherapy) | 22.6 |
Overall Response Rate (PR + CR)
Overall response rate (CR and PR) after 3 cycles of C R ICE in patients age of 18 to 75 with relapsed/refractory CD20-positive DLBCL treated with rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, R-HyperCVAD, etc.) induction. Response was based on a Modified Cheson Criteria with Complete response (CR): All lesions with a longest diameter ≤ 15 mm or short axis ≤ 10 mm (Not palpable during the clinical examination, No visible nodule on imaging, And disappearance of all non-nodal target lesions Or in case of hypermetabolic disease on the baseline PET scan, negative PET scan whatever the appearance of lesions on CT) and Partial Response (PR): ≥ 50 % of sum of the products of the diameters (SPD) of target lesions or in the case of hypermetabolic lesions on the baseline PET scan, persistence of at least one PET-positive site without progression of other lesions on CT (≥ 50 % of SPD of target lesions (or longest diameter if a single nodule) No clinically enlarged liver or spleen) (NCT01959698)
Timeframe: The time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented, assessed up to 12 weeks
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Carfilzomib, Rituximab, Chemotherapy) | 66 |
MTD Defined as the Dose of Carfilzomib Added to Standard R-ICE Chemotherapy Which, if Exceeded, Would Put the Patient at an Undesirable Risk of Medically Unacceptable Dose-limiting Toxicities (Phase I)
(NCT01959698)
Timeframe: 28 days
| Intervention | mg/m2 (Number) |
|---|
| Dose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9) | NA |
| Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9) | NA |
| Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9) | NA |
| Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9) | NA |
| Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9) | NA |
| Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9) | NA |
| Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9) | NA |
Complete Response Rate According to the International Working Group Response Criteria as Reported by the Revised Cheson Criteria
Efficacy rates were estimated using simple relative frequencies. Complete response rate after 3 cycles of C R ICE in patients age of 18 to 75 with relapsed/refractory CD20-positive DLBCL treated with rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, R-HyperCVAD, etc.) induction. Response was based on a Modified Cheson Criteria with Complete response (CR): All lesions with a longest diameter ≤ 15 mm or short axis ≤ 10 mm (Not palpable during the clinical examination, No visible nodule on imaging, And disappearance of all non-nodal target lesions Or in case of hypermetabolic disease on the baseline PET scan, negative PET scan whatever the appearance of lesions on CT) and Partial Response (PR): ≥ 50 % of sum of the products of the diameters (SPD) of target lesions or in the case of hypermetabolic lesions on the baseline PET scan, persistence of at least one PET-positive site without progression of other lesions on CT (≥ 50 % of SPD of target lesions (or longest diameter if a si (NCT01959698)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Carfilzomib, Rituximab, Chemotherapy) | 48 |
Toxicity of the Addition of Carfilzomib to R-ICE at the MTD, Assessed by the CTEP Version 4.0 of the NCI CTCAE
Count of participants that experienced serious adverse events assessed by the CTEP version 4.0 of the NCI CTCAE (NCT01959698)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Dose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9) | 2 |
| Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9) | 0 |
| Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9) | 0 |
| Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9) | 1 |
| Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9) | 1 |
| Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9) | 3 |
| Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9) | 4 |
Prognostic Significance of Minimal Residual Disease
Analyzed by estimating the 2-year EFS of negative MRD and positive MRD by arm. Minimal disease was performed using serial assessments of the t(2;5)(p23;q35) NPM-ALK fusion transcript using quantitative RT-PCR. Quantitative RT-PCR was performed by extracting total RNA from peripheral blood specimens. Peripheral blood samples were obtained at baseline, on day 1 of cycle 1, and on day 1 of cycle 2. The normalized copy numbers (NCN) were expressed as copy numbers of NPM-ALK per 104 copies of ABL. Minimal disease (MDD) was defined as >10 NCN at baseline. (NCT01979536)
Timeframe: Baseline up to progressive disease, relapse, or death, assessed up to 2 years
| Intervention | Percentage of patients (Number) |
|---|
| MRD Negative Arm BV (Brentuximab Vedotin, Combination Chemotherapy) | 89 |
| MRD Positive Arm BV (Brentuximab Vedotin, Combination Chemotherapy) | 52.6 |
| MRD Negative Arm CZ (Crizotinib, Combination Chemotherapy) | 85.6 |
| MRD Positive Arm CZ (Crizotinib, Combination Chemotherapy) | 58.1 |
Occurrence of Grade 3+ Non-hematologic Adverse Events
Will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicities will be summarized by individual toxicity counts separated by arm. (NCT01979536)
Timeframe: Up to 60 months
| Intervention | Percentage of patients (Number) |
|---|
| Arm BV (Brentuximab Vedotin, Combination Chemotherapy) | 80.6 |
| Arm CZ (Crizotinib, Combination Chemotherapy) | 87.9 |
Event Free Survival (EFS)
The Kaplan-Meier method will be used to estimate the 2-year EFS for each of the treatment regimens. (NCT01979536)
Timeframe: Time from study entry until progressive disease, relapse, or death, assessed up to 2 years
| Intervention | Percentage of patients (Number) |
|---|
| Arm BV (Brentuximab Vedotin, Combination Chemotherapy) | 78.8 |
| Arm CZ (Crizotinib, Combination Chemotherapy) | 76.8 |
Distant Disease-free Survival (Stage IIB-III Patients)
Time from registration to development of distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier used. (NCT02050919)
Timeframe: Time from registration until development of distant metastatic disease or death, whichever occurs first, assessed up to 2 years
| Intervention | Months (Median) |
|---|
| Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) | 16.4 |
Number of Participants With Wound Complications
Wound complication rate, including 1) any secondary operation for wound repair, or 2) wound management without secondary operation including invasive procedures without general or regional anesthesia, readmission for wound care, or persistent deep packing for 120 days or longer. (NCT02050919)
Timeframe: At least 120 days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) | 10 |
Overall Disease-free Survival (Stage IIB-III Patients)
Time from surgical resection to local recurrence, distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier used. (NCT02050919)
Timeframe: Time from surgical resection to local recurrence, distant metastatic disease, or death, whichever occurs first, assessed up to 2 years
| Intervention | Months (Median) |
|---|
| Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) | 13.3 |
Overall Survival at 2 Years
Percentage of patients alive at 2 years, Method of Kaplan-Meier used. (NCT02050919)
Timeframe: Time from registration until death from any cause
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) | 82 |
Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis.
Descriptive statistical analysis will be conducted. The proportion with 95% confidence interval will be summarized. (NCT02050919)
Timeframe: Assessed at surgical resection
| Intervention | % of participants (Number) |
|---|
| Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) | 20 |
Number of Participants With Local Recurrence
Number of patients with local recurrence after surgical resection of the primary tumor (NCT02050919)
Timeframe: Time from surgical resection until primary analysis ( Median follow-up for local recurrence 17.11 months, range 6.18 - 42.8 months)
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) | 0 |
Number of Grade 3-4 Adverse Events
Measured as the number of Grade 3-4 Adverse Events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (NCT02050919)
Timeframe: Up to 5 years
| Intervention | Grade 3-4 Adverse Events (Number) |
|---|
| Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) | 86 |
EFS for Very High Risk (VHR) T-ALL Patients Treated With High Risk (HR) Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Become Minimal Residual Disease (MRD) Negative and Those Who Remain MRD Positive at the End of HR Block 3
EFS will be calculated as time from the end of the three high-risk blocks of therapy to first event (relapse, second malignancy, remission death) or date of last contact. (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| VHR T-ALL MRD Undetectable | 25.0 |
| VHR T-ALL MRD Detectable | 88.9 |
EFS for Very High Risk (VHR) T-LLy Patients Treated With HR Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Have Complete or Partial Remission and Those Who do Not Respond
EFS for very high risk (VHR) T-LLy patients treated with HR Berlin-Frankfurt-Munster (BFM) intensification blocks who have complete or partial remission and those who do not respond (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| VHR T-LLy (CR/PR) | 0 |
Event-free Survival (EFS) for Modified Augmented Berlin-Frankfurt-Munster Backbone With or Without Bortezomib in All Randomized Patients
EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact. Three-year EFS rates will be calculated for both groups. (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Arm A (Combination Chemotherapy) | 81.7 |
| Arm B (Combination Chemotherapy, Bortezomib) | 85.1 |
Toxicity Rates Associated With Modified Standard Therapy, Including Dexamethasone and Additional Pegaspargase
Percentage of patients who experienced Grade 3 or higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (NCT02112916)
Timeframe: 3 years from start of therapy by patient
| Intervention | Percentage of participants (Number) |
|---|
| Total Patients | 78.0 |
Cumulative Incidence Rates of Isolated Central Nervous System (CNS) Relapse for SR and IR T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no CRT) and Similar Patients on AALL0434 (Receive CRT)
Cumulative incidence of isolated CNS relapse adjusting for competing risks using the method of: Gray R, A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1141:1154, 1988 (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Isolated CNS Relapse | Isolated Bone Marrow Relapse | Combined Bone Marrow Relapse |
|---|
| AALL0434 T-ALL Patients | 2.2 | 3.0 | 1.8 |
,| AALL1231 T-ALL Patients | 3.6 | 1.4 | 1.3 |
Feasible Dose: Pediatric
The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and < 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered. (NCT02180867)
Timeframe: After the first 6 weeks of Induction
| Intervention | milligram per square meter (Number) |
|---|
| All Pediatric Dose Finding CR Cohorts | 350 |
| All Pediatric Dose Finding RT Cohorts | 450 |
Feasible Dose: Adult
The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in adult unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and < 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered. (NCT02180867)
Timeframe: After the first 6 weeks of Induction
| Intervention | milligram (Number) |
|---|
| All Adult Dose Finding CR Cohorts | 600 |
| All Adult Dose Finding RT Cohorts | 800 |
Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10
A responder is defined by more than 90% tumor necrosis at week 10. A non-responder has less than 90% necrosis or progressive disease before week 10. (NCT02180867)
Timeframe: Week 10 after induction
| Intervention | Percentage of patients (Number) |
|---|
| Dose-Finding Level 1 RT | 0 |
| Dose-Finding Level 2 RT | 40 |
| Regimen C | 0 |
| Regimen D | 0 |
Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Participants who experienced Grade 3 or higher toxicity was assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). (NCT02180867)
Timeframe: Reporting of adverse events was required from the start of protocol therapy and until 30 days from the last administration of study drugs; up to 1 year
| Intervention | Percentage of patients (Number) |
|---|
| Pediatric Patients | Adult Patients |
|---|
| Dose-Finding Level 1 CR | 60 | 75 |
,| Dose-Finding Level 1 RT | 66.67 | 66.67 |
,| Dose-Finding Level 2 RT | 33.33 | 57.14 |
,| Regimen A | 75 | 86.67 |
,| Regimen B | 33.33 | 36 |
,| Regimen C | 0 | 40 |
Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Participants who experienced Grade 3 or higher toxicity was assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). (NCT02180867)
Timeframe: Reporting of adverse events was required from the start of protocol therapy and until 30 days from the last administration of study drugs; up to 1 year
| Intervention | Percentage of patients (Number) |
|---|
| Adult Patients |
|---|
| Regimen D | 0 |
Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13
A responder is defined by more than (90% tumor necrosis at week 13). A non-responder has less than 90% necrosis or progressive disease before week 13. (NCT02180867)
Timeframe: Week 13 after induction
| Intervention | Percentage of patients (Number) |
|---|
| Dose-Finding Level 1 CR | 66.67 |
| Regimen A | 46.67 |
| Regimen B | 24 |
2 Year Overall Survival
(NCT02227199)
Timeframe: Up to 2 years from initiation of study therapy.
| Intervention | Participants (Count of Participants) |
|---|
| Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | 3 |
| Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | 3 |
| Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | 37 |
2 Year Progression-free Survival
(NCT02227199)
Timeframe: Up to 2 years from initiation of therapy.
| Intervention | Participants (Count of Participants) |
|---|
| Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | 2 |
| Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | 3 |
| Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | 33 |
Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy
Will be defined as the dose at which =< 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. (NCT02227199)
Timeframe: Up to 28 days following the second course of chemotherapy, approximately 70 days
| Intervention | mg/kg (Number) |
|---|
| Treatment (Brentuximab, Ifosfamide, Carboplatin, Etoposide) | 1.5 |
Percentage of Patients That Achieve a Complete Remission Following Study Treatment
(NCT02227199)
Timeframe: 3 weeks following the completion of chemotherapy
| Intervention | Participants (Count of Participants) |
|---|
| Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | 3 |
| Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | 3 |
| Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | 26 |
Overall Survival
Time from study enrollment to death or last patient contact. (NCT02306161)
Timeframe: 5 years after enrollment
| Intervention | Percent Probability (Number) |
|---|
| Regimen A (VDC/IE) | 44.93 |
| Regimen B (VDC/IE + Ganitumab) | 48.19 |
Frequency of Toxicity-events
The number of induction or consolidation reporting periods in which a CTC version 4 codeable grade 4 or greater non-hematological adverse event, grade 3 or greater left ventricular systolic dysfunction or the reporting period is terminated because of a CTC codeable event. (NCT02306161)
Timeframe: Up to 202 days
| Intervention | Reporting Periods (Number) |
|---|
| Regimen A (VDC/IE) | 10 |
| Regimen B (VDC/IE + Ganitumab) | 27 |
Event-free Survival
Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact. (NCT02306161)
Timeframe: 5 years after enrollment
| Intervention | percent probability of participants (Number) |
|---|
| Regimen A (VDC/IE) | 30.88 |
| Regimen B (VDC/IE + Ganitumab) | 30.4 |
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores
KPS: compare effectiveness of medicine for disease and assess outcomes in participants. KPS Scores: recorded on 11 point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100%), where 0=Dead; 10=moribund, fatal processes progressing rapidly; 20=very sick, hospital admission necessary, active supportive treatment necessary; 30=severely disabled, hospital admission is indicated although death not imminent; 40=disabled, requires special care/assistance; 50=requires considerable assistance/frequent medical care; 60=requires occasional assistance, but is able to care for personal needs; 70=cares for self, unable to carry normal activity or active work; 80=normal activity with effort, some signs of disease; 90=able to carry on normal activity, minor signs of disease; 100=normal no complaints, no evidence of disease. Lower score, worse survival for most serious illnesses. (NCT02432274)
Timeframe: Baseline up to approximately 4 years 7 months
| Intervention | Participants (Count of Participants) |
|---|
| Baseline score: 100%, Worst Postbaseline score:80% | Baseline score: 100%, Worst Postbaseline score:90% | Baseline score: 70%, Worst Postbaseline score: 70% | Baseline score: 90%, Worst Postbaseline score: 70% | Baseline score: 80%, Worst Postbaseline score: 80% | Baseline score: 90%, Worst Postbaseline score: 60% | Baseline score:100%, Worst Postbaseline score:100% | Baseline score: 100%, Worst Postbaseline score:70% | Baseline score: 90%, Worst Postbaseline score: 80% | Baseline score: 90%, Worst Postbaseline score: 90% |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 2 | 2 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 1 |
,| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 2 | 2 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 3 |
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib
In acceptability questionnaire, participants were asked to answer the overall acceptability of lenvatinib suspension considering the following elements: taste, appearance, smell and how does it feel in the mouth. Overall acceptability was answered in terms of 7 responses: Super good, really good, good, may be good or may be bad, bad, really bad, super bad. Overall acceptability was the overall acceptance for taste, appearance, smell, and the feeling in mouth. In this measure, number of participants have been reported per their overall acceptability responses. (NCT02432274)
Timeframe: Cycle 1 Day 1 (Cycle length=28 days for Cohorts 1, 2A, 2B; Cycle length=21 days for Cohorts 3A, 3B)
| Intervention | Participants (Count of Participants) |
|---|
| Super Good | Really Good | Good | May be Good or May be Bad | Bad | Really Bad | Super Bad |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
,| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
,| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 0 | 0 | 1 | 1 | 1 | 1 | 0 |
,| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level
"Serum biomarkers included Fibroblast Growth Factor (FGF) 19, FGF 21, Vascular Endothelial Growth Factor (VEGF). In this outcome measure, percent change from baseline in serum biomarkers level per PFS-4, Yes and PFS-4, No have been reported. As per assessment of investigator based on RECIST v1.1, PFS-4, Yes= participants evaluable for PFS-4 month and alive and without PD at 4 months from the first dose, PFS-4, No=participants evaluable for PFS-4 month and not alive or with PD at 4 months from the first dose." (NCT02432274)
Timeframe: Cohort 2B: Baseline, Cycle 2-3 Day 1 (Duration of each cycle=28 days); Cohort 3B: Baseline, Cycle 2 Day 1, Cycle 4 Day 1 (Duration of each cycle=21 days)
| Intervention | percent change (Mean) |
|---|
| C2D1: FGF 19 (PFS-4, Yes) | C2D1: FGF 19 (PFS-4, No) | C3D1: FGF 19 (PFS-4, Yes) | C3D1: FGF 19 (PFS-4, No) | C2D1: FGF 21 (PFS-4, Yes) | C2D1: FGF 21 (PFS-4, No) | C3D1: FGF 21 (PFS-4, Yes) | C3D1: FGF 21 (PFS-4, No) | C2D1: VEGF (PFS-4, Yes) | C2D1: VEGF (PFS-4, No) | C3D1: VEGF (PFS-4, Yes) | C3D1: VEGF (PFS-4, No) |
|---|
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 48.7 | 109.9 | 47.3 | 194.5 | -14.9 | 134.3 | 55.0 | 17.0 | 119.9 | 124.2 | 64.3 | 23.2 |
Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level
"Serum biomarkers included Fibroblast Growth Factor (FGF) 19, FGF 21, Vascular Endothelial Growth Factor (VEGF). In this outcome measure, percent change from baseline in serum biomarkers level per PFS-4, Yes and PFS-4, No have been reported. As per assessment of investigator based on RECIST v1.1, PFS-4, Yes= participants evaluable for PFS-4 month and alive and without PD at 4 months from the first dose, PFS-4, No=participants evaluable for PFS-4 month and not alive or with PD at 4 months from the first dose." (NCT02432274)
Timeframe: Cohort 2B: Baseline, Cycle 2-3 Day 1 (Duration of each cycle=28 days); Cohort 3B: Baseline, Cycle 2 Day 1, Cycle 4 Day 1 (Duration of each cycle=21 days)
| Intervention | percent change (Mean) |
|---|
| C2D1: FGF 19 (PFS-4, Yes) | C2D1: FGF 19 (PFS-4, No) | C4D1: FGF 19 (PFS-4, Yes) | C4D1: FGF 19 (PFS-4, No) | C2D1: FGF 21 (PFS-4, Yes) | C2D1: FGF 21 (PFS-4, No) | C4D1: FGF 21 (PFS-4, Yes) | C4D1: FGF 21 (PFS-4, No) | C2D1: VEGF (PFS-4, Yes) | C2D1: VEGF (PFS-4, No) | C4D1: VEGF (PFS-4, Yes) |
|---|
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 172.1 | 78.3 | 237.7 | 91.9 | 70.2 | 7.2 | 256.2 | -1.5 | 87.9 | 95.8 | 84.3 |
Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR)
DOR was defined as time in months from the first documentation confirmed CR or PR until the first documentation of confirmed PD as assessed by investigator based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. 95% CI for the median were calculated according to Brookmeyer and Crowley method. (NCT02432274)
Timeframe: First documentation of CR/PR until first documentation of PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
| Intervention | months (Median) |
|---|
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 1.9 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 4.6 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | NA |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | NA |
Cohort 3A: Recommended Dose (RD) of Lenvatinib When Given in Combination With Etoposide and Ifosfamide
RD of lenvatinib when given in combination with ifosfamide and etoposide was defined as dose that resulted in no more than 1 DLT per 6 participants,or hematologic DLT in 1 participant and nonhematologic DLT in another participant per 6 participants,upon repeating same dose level.DLT was adverse drug reaction and assessed per CTCAE v4.03 defined as 1)Grade 4 neutropenia for >=10 days,2)Grade >=3 thrombocytopenia with bleeding,or lasting >=10 days,3)Grade >=3 febrile neutropenia lasting >=7 days,4)Next course of chemotherapy delayed for >=7 days,5)Grade >=3 nonhematologic toxicity persisting >7 days despite optimal supportive care,6)Grade 4 hypertension,confirmed systolic or diastolic blood pressure >25 mmHg above 95th percentile for age,or elevated diastolic blood pressure(>95th percentile for age)not controlled by single antihypertensive medication within 14 days use,7)Grade 3 proteinuria,8)Any recurrent Grade 2 nonhematological toxicity requiring >=2 interruption and dose reductions. (NCT02432274)
Timeframe: Cycle 1 (21 days)
| Intervention | milligram per square meter (mg/m^2) (Number) |
|---|
| Cohort 3A: All Participants | 14 |
Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR)
OR was defined as participants with best overall response (BOR) of CR or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. For OR, the BOR was defined as the best response (CR or PR for >4 weeks) recorded from the start of the treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. (NCT02432274)
Timeframe: From date of first dose of study drug until first documentation of PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 1 |
Cohort 1: Recommended Dose (RD) of Lenvatinib
RD was defined as the dose that had a dose limiting toxicity (DLT) rate closest to the targeted 20% rate. DLT was an adverse drug reaction and was assessed according to common terminology criteria for adverse events (CTCAE) version (v) 4.03 defined as 1) Grade 4 neutropenia for greater than or equal to (>=) 7 days, 2) Grade >=3 thrombocytopenia with bleeding, or lasting greater than (>) 7 days, 3) Grade >=3 febrile neutropenia, 4) Next course of chemotherapy delayed for >=7 days, 5) Grade >=3 non-hematologic toxicity persisting >7 days optimal supportive care, 6) Grade 4 hypertension, confirmed systolic or diastolic blood pressure >25 millimeters of mercury (mmHg) above the 95th percentile for age, or an elevated diastolic blood pressure (that is, >95th percentile for age) not controlled by a single antihypertensive medication within 14 days of use, 7) Grade 3 proteinuria, 8) Any recurrent Grade 2 non-hematological toxicity requiring >=2 interruption and dose reductions. (NCT02432274)
Timeframe: Cycle 1 (28 days)
| Intervention | milligram per square meter (mg/m^2) (Number) |
|---|
| Cohort 1: All Participants | 14 |
Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP)
TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD based on RECIST 1.1. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method. (NCT02432274)
Timeframe: From first dose of study drug until PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
| Intervention | months (Median) |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 3.7 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 6.3 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 5.5 |
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 5.5 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 3.0 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 7.1 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 12.0 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 6.9 |
Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR)
BOR: best response of CR or PR for >4 weeks or SD for >=7 weeks from first dose, recorded from start of treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have reduction in their short axis <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Not evaluable (NE) means BOR of NE or SD of <7 weeks duration. Unknown means no data were available on the case report form. (NCT02432274)
Timeframe: From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Not Evaluable or Unknown |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 0 | 0 | 2 | 1 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 0 | 0 | 5 | 2 | 2 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 0 | 0 | 4 | 4 | 2 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 0 | 2 | 3 | 2 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 0 | 0 | 10 | 2 | 2 |
,| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 0 | 3 | 9 | 4 | 2 |
,| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 0 | 2 | 13 | 12 | 3 |
Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib
Duration of each cycle for Cohorts 1, 2A, 2B is 28 days. Duration of each cycle for Cohorts 3A, 3B is 21 days. (NCT02432274)
Timeframe: Cohorts 1, 2A, 2B: Cycle(C)1 Day(D)1: 0.5-4 hours (h), 6-10 h post-dose, C1D15: pre-dose, 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose; Cohorts 3A, 3B: C1D1: 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| Cycle 1 Day 1: 0.5-4 hours | Cycle 1 Day 1: 6-10 hours | Cycle 1 Day 15: Pre-dose | Cycle 1 Day 15: 0.5-4 hours | Cycle 1 Day 15: 6-10 hours | Cycle 2 Day 1: Pre-dose | Cycle 2 Day 1: 2-12 hours |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 295.6 | 212.7 | 46.9 | 133.4 | 351.8 | 58.1 | 502.4 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 134.8 | 281.9 | 59.1 | 226.6 | 375.8 | 61.6 | 440.7 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 52.5 | 238.0 | 96.9 | 191.8 | 413.0 | 97.9 | 339.2 |
,| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 11.1 | 188 | 56.2 | 124 | 247 | 59.8 | 102 |
,| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 177.4 | 289.4 | 67.0 | 168.3 | 322.9 | 66.8 | 382.4 |
Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib
Duration of each cycle for Cohorts 1, 2A, 2B is 28 days. Duration of each cycle for Cohorts 3A, 3B is 21 days. (NCT02432274)
Timeframe: Cohorts 1, 2A, 2B: Cycle(C)1 Day(D)1: 0.5-4 hours (h), 6-10 h post-dose, C1D15: pre-dose, 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose; Cohorts 3A, 3B: C1D1: 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| Cycle 1 Day 1: 0.5-4 hours | Cycle 1 Day 1: 6-10 hours | Cycle 2 Day 1: Pre-dose | Cycle 2 Day 1: 2-12 hours |
|---|
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 105.2 | 191.9 | 51.7 | 205.6 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 111.4 | 148.5 | 76.1 | 237.4 |
,| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 209.7 | 164.8 | 50.4 | 275.3 |
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit
Participants were defined as having clinical benefit if they had a BOR of CR or PR for >4 weeks or durable SD (lasting >=23 weeks) or if participants had a BOR of CR or durable Non-CR/Non-PD (lasting >=23 weeks) as per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target/non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. Non-CR/Non-PD:persistence of 1 or more non-target lesions and maintenance of tumor marker level above the normal limits. (NCT02432274)
Timeframe: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 0 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 3 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 4 |
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 1 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 7 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 4 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 5 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 8 |
Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a BOR of CR or PR for >4 weeks or SD for >=7 weeks as assessed by investigator based on RECIST v1.1, recorded from start of study treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. 95% CI of the ORR were calculated according to Clopper and Pearson method. (NCT02432274)
Timeframe: From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
| Intervention | percentage of participants (Number) |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 0 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 0 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 0 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 6.7 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 28.6 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 0 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 16.7 |
Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS)
PFS was defined as the time (in months) from the date of first dose of study drug to the date of first documentation of PD or date of death, whichever occurred first, based on RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method. (NCT02432274)
Timeframe: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
| Intervention | months (Median) |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 3.7 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 6.3 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 5.5 |
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 5.5 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 3.0 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 7.1 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 12.0 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 6.9 |
Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS)
OS was defined as the time from the date of the first dose of study drug until the date of death from any cause. Participants who are lost to follow-up and those who are alive at the date of data cutoff were censored at the date the participant was last known to be alive (or the data cutoff date). 95% CI of median were calculated according to Brookmeyer and Crowley method. (NCT02432274)
Timeframe: From first dose of study drug until death (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
| Intervention | months (Median) |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 8.1 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 7.4 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 7.7 |
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 6.1 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 10.0 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 13.6 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | NA |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | NA |
Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4
Progression free survival at Month 4 (PFS-4) rate was defined as the percentage of participants who were alive and without PD at Month 4 after the first dose of study drug, based on RECIST v1.1, using a binomial proportion with corresponding 95% confidence interval (CI). PD: >= 20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of >=5 mm. Appearance of >=1 new lesions also considered PD. (NCT02432274)
Timeframe: At Month 4
| Intervention | percentage of participants (Number) |
|---|
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 32.1 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 66.7 |
Cohort 2A: Number of Participants With Best Overall Response (BOR)
BOR was defined as the best response of CR or PR for >4 weeks or SD for >=7 weeks recorded from the start of the treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. (NCT02432274)
Timeframe: From first dose of study drug until PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Stable Disease |
|---|
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 0 | 1 | 0 |
Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria
"An aliquot of the urine samples were collected to analyze protein by dipstick method, microscopic examination (if protein was abnormal). The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters of urine protein can be read as negative, Trace, plus (+) 1, +2, +3 and +4 indicating proportional concentrations in the urine sample. The plus sign increases with a higher level of proteins in the urine." (NCT02432274)
Timeframe: Baseline up to approximately 4 years 7 months
| Intervention | Participants (Count of Participants) |
|---|
| Baseline: Trace, Worst Post baseline: Negative | Baseline: Trace, Worst Post baseline: Trace | Baseline: +1, Worst Post baseline: Negative | Baseline: +1, Worst Post baseline: +1 | Baseline: Negative, Worst Post baseline: Negative | Baseline: +2, Worst Post baseline: Negative | Baseline: +3, Worst Post baseline: Negative | Baseline: +3, Worst Post baseline: +1 | Baseline: +3, Worst Post baseline: +2 | Baseline: +3, Worst Post baseline: Trace | Baseline: +4, Worst Post baseline: Trace | Baseline: +4, Worst Post baseline: +1 | Baseline: Negative, Worst Post baseline: Trace | Baseline: Negative, Worst Post baseline: +1 | Baseline: Negative, Worst Post baseline: +2 | Baseline: Negative, Worst Post baseline: +3 | Baseline: Trace, Worst Post baseline: +1 | Baseline: Trace, Worst Post baseline: +2 | Baseline: Trace, Worst Post baseline: +3 | Baseline: +1, Worst Post baseline: Trace | Baseline: +1, Worst Post baseline: +2 | Baseline: +1, Worst Post baseline: +3 | Baseline: Negative, Worst Post baseline: +4 | Baseline: +1, Worst Post baseline: +4 |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 2 | 0 | 3 | 0 | 1 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 0 | 1 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
,| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 6 | 2 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 1 |
,| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 0 | 1 | 0 | 0 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 5 | 7 | 1 | 1 | 2 | 1 | 1 | 1 | 3 | 1 | 0 | 0 |
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Number of participants with TEAEs (serious and non-serious adverse events) and SAEs were reported based on their safety assessments of hematology, clinical chemistry, proximal tibial growth, fecal occult blood, physical examinations, regular measurement of vital signs and electrocardiogram parameter values. (NCT02432274)
Timeframe: From the date of first dose of study drug up to 30 days after the last dose (up to approximately 7 years)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | SAEs |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 5 | 3 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 11 | 7 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 7 | 5 |
,| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 1 | 1 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 11 | 7 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 11 | 9 |
,| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 20 | 16 |
,| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 29 | 21 |
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score
Lansky Performance Play Scale rates a child's activity level for <16 years of age. Scores on scale range from 0 (unresponsive) to 100 ( fully active, normal), where 100=fully active, normal; 90=minor restrictions in physically strenuous activity; 80=active, but tires more quickly; 70=both greater restriction of and less time spent in play activity; 60=up and around, but minimal active play, keeps busy with quieter activities; 50=gets dressed, but lies around much of day, no active play, able to participant in quiet play and activities; 40=mostly in bed, participates in quiet activities; 30=in bed, needs assistance even for quiet play; 20=often sleeping, play entirely limited to very passive activities; 10=no play, does not get out of bed; 0=unresponsive. Higher score indicates more activity and lower indicates less or no activity. (NCT02432274)
Timeframe: Baseline up to approximately 4 years 7 months
| Intervention | Participants (Count of Participants) |
|---|
| Baseline score:100%, Worst Postbaseline score:90% | Baseline score: 70%, Worst Postbaseline score: 60% | Baseline score: 80%, Worst Postbaseline score: 60% | Baseline score: 100%, Worst Postbaseline score:60% | Baseline score: 80%, Worst Postbaseline score: 70% | Baseline score: 90%, Worst Postbaseline score: 70% | Baseline score: 90%, Worst Postbaseline score: 80% | Baseline score:100%, Worst Postbaseline score:100% | Baseline score: 80%, Worst Postbaseline score: 40% | Baseline score: 70%, Worst Postbaseline score: 80% | Baseline score: 80%, Worst Postbaseline score: 80% | Baseline score: 100%, Worst Postbaseline score:80% | Baseline score: 90%, Worst Postbaseline score: 90% | Baseline score: 60%, Worst Postbaseline score: 60% | Baseline score: 90%, Worst Postbaseline score: 60% | Baseline score: 70%, Worst Postbaseline score: 70% | Baseline score: 90%, Worst Postbaseline score:100% | Baseline score: 100%, Worst Postbaseline score:70% | Baseline score: 80%, Worst Postbaseline score: 50% |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
,| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
,| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 | 0 | 4 | 1 | 1 | 1 | 1 | 0 | 1 |
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control
Participants were defined as having disease control if they had a BOR of CR or PR for >4 weeks, or SD (minimum duration from first dose to SD >=7 weeks) or if participants had a BOR of CR or Non-CR/Non-PD (minimum duration from first dose to Non-CR/Non-PD >=7 weeks) per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (target/non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest SOD. Non-CR/Non-PD: persistence of 1 or more non-target lesions, maintenance of tumor marker level above the normal limits. (NCT02432274)
Timeframe: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 2 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 5 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 5 |
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 1 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 16 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 5 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 11 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 14 |
Number of Participants With Complete Response (CR) of Rolapitant Hydrochloride Administered as a Single-dose
Complete response (CR) no emetic episodes and no rescue medications. (NCT02732015)
Timeframe: Days 1-10
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 | 0 |
| Cohort 2 | 5 |