Page last updated: 2024-10-20

pteridines and Metastase

pteridines has been researched along with Metastase in 7 studies

Research Excerpts

ExcerptRelevanceReference
" Treatment of syngeneic R3T or 4T1 tumor-bearing mice with orally given SD-208 inhibited primary tumor growth as well as the number and size of metastases."3.73Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo. ( Barnard, N; Chakravarty, J; Dugar, S; Ge, R; Lattime, E; Medicherla, S; Murphy, A; Protter, A; Rajeev, V; Ray, P; Reiss, M; Rittling, S; Schreiner, G, 2006)
"To determine the maximum tolerated dose (MTD) of volasertib, a Polo-like kinase inhibitor, combined with afatinib, an oral irreversible ErbB family blocker, in patients with advanced solid tumors (NCT01206816; Study 1230."2.80A phase I study of volasertib combined with afatinib, in advanced solid tumors. ( De Smet, M; Herremans, C; Liu, D; Machiels, JP; Peeters, M; Pilz, K; Rottey, S; Specenier, P; Strelkowa, N; Surmont, V, 2015)

Research

Studies (7)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's1 (14.29)29.6817
2010's6 (85.71)24.3611
2020's0 (0.00)2.80

Authors

AuthorsStudies
Breitenbuecher, F1
von Pawel, J1
Sebastian, M1
Kortsik, C1
Ting, S1
Kasper, S1
Wohlschläger, J1
Worm, K1
Morresi-Hauf, A1
Schad, A1
Westerwick, D1
Wehler, B1
Werner, M1
Munzert, G1
Gaschler-Markefski, B1
Schmid, KW1
Schuler, M1
Stone, A1
Cowley, MJ1
Valdes-Mora, F1
McCloy, RA1
Sergio, CM1
Gallego-Ortega, D1
Caldon, CE1
Ormandy, CJ1
Biankin, AV1
Gee, JM1
Nicholson, RI1
Print, CG1
Clark, SJ1
Musgrove, EA1
Fan, L1
Li, P1
Yin, Z1
Fu, G1
Liao, DJ1
Liu, Y1
Zhu, J1
Zhang, Y1
Wang, L1
Yan, Q1
Guo, Y1
Shao, C1
Huang, G1
Wang, Z1
Stadler, WM1
Vaughn, DJ1
Sonpavde, G1
Vogelzang, NJ1
Tagawa, ST1
Petrylak, DP1
Rosen, P1
Lin, CC1
Mahoney, J1
Modi, S1
Lee, P1
Ernstoff, MS1
Su, WC1
Spira, A1
Pilz, K2
Vinisko, R1
Schloss, C1
Fritsch, H1
Zhao, C1
Carducci, MA1
Machiels, JP1
Peeters, M1
Herremans, C1
Surmont, V1
Specenier, P1
De Smet, M1
Strelkowa, N1
Liu, D1
Rottey, S1
Kaneda, MM1
Cappello, P1
Nguyen, AV1
Ralainirina, N1
Hardamon, CR1
Foubert, P1
Schmid, MC1
Sun, P1
Mose, E1
Bouvet, M1
Lowy, AM1
Valasek, MA1
Sasik, R1
Novelli, F1
Hirsch, E1
Varner, JA1
Ge, R1
Rajeev, V1
Ray, P1
Lattime, E1
Rittling, S1
Medicherla, S1
Protter, A1
Murphy, A1
Chakravarty, J1
Dugar, S1
Schreiner, G1
Barnard, N1
Reiss, M1

Clinical Trials (3)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
An Open-label, Single-arm, Phase II Trial of Intravenous BI 6727 in Patients With Locally Advanced, Metastatic or Recurrent Urothelial Cancer of the Bladder, Renal Pelvis, or Ureters After Failure of Prior Chemotherapy[NCT01023958]Phase 250 participants (Actual)Interventional2009-11-19Completed
An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 in Combination With Oral BIBW 2992 in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit[NCT01206816]Phase 157 participants (Actual)Interventional2010-10-04Completed
Phase 2 Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma[NCT03795610]Phase 215 participants (Anticipated)Interventional2020-03-06Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

AUC0-∞ of Volasertib

Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of volasertib (NCT01023958)
Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Interventionng*h/mL (Geometric Mean)
Volasertib (BI 6727)5470

CL of Volasertib

Total plasma clearance after intravascular administration (CL) of volasertib (NCT01023958)
Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

InterventionmL/min (Geometric Mean)
Volasertib (BI 6727)914

Cmax of Volasertib

Maximum measured concentration in plasma (Cmax) of volasertib (NCT01023958)
Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Interventionng/mL (Geometric Mean)
Volasertib (BI 6727)253

Disease Control Rate

Disease control rate. Disease control is defined as having a best overall response of complete response (CR), partial response (PR) or stable disease (SD). (NCT01023958)
Timeframe: From first drug administration until end of study, up to 2 years

InterventionPercentage of participants (Number)
Volasertib (BI 6727)40.0

Duration of Disease Control

Disease control is defined as having a best overall response of CR, PR, or SD. The duration of disease control is measured from the time of first response to progression or death whichever occurs first. (NCT01023958)
Timeframe: Time of first response to progression or death, up to 2 years

InterventionWeeks (Median)
Volasertib (BI 6727)27.0

Duration of Overall Response

The duration of overall response is measured from the time of first response (CR or PR) to progression or death whichever occurs first. (NCT01023958)
Timeframe: From the time of first response (CR or PR) to progression or death, up to 2 years

InterventionWeeks (Median)
Volasertib (BI 6727)41.0

Laboratory Investigation: Alkaline Phosphatase

Difference from baseline in laboratory parameter Alkaline phosphatase (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

InterventionU/L (Mean)
Volasertib (BI 6727)35

Laboratory Investigation: ALT/GPT, SGPT

Difference from baseline in laboratory parameter Alanine aminotransferase(ALT)/GPT, SGPT (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

InterventionU/L (Mean)
Volasertib (BI 6727)3

Laboratory Investigation: AST/GOT, SGOT

Difference from baseline in laboratory parameter Aspartate aminotransferase(AST)/GOT, SGOT (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

InterventionU/L (Mean)
Volasertib (BI 6727)5

Laboratory Investigation: Creatinine

Difference from baseline in laboratory parameter Creatinine (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

Interventionumol/L (Mean)
Volasertib (BI 6727)16

Laboratory Investigation: Haemoglobin

Difference from baseline in laboratory parameter Haemoglobin (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

Interventiong/L (Mean)
Volasertib (BI 6727)-19

Laboratory Investigation: Lymphocytes

Difference from baseline in laboratory parameter Lymphocytes (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

Intervention10^9 cells/L (Mean)
Volasertib (BI 6727)-0.8

Laboratory Investigation: Neutrophils

Difference from baseline in laboratory parameter Neutrophils (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

Intervention10^9 cells/L (Mean)
Volasertib (BI 6727)-1.9

Laboratory Investigation: Platelets

Difference from baseline in laboratory parameter Platelets (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

Intervention10^9 cells/L (Mean)
Volasertib (BI 6727)-23

Laboratory Investigation: Total Bilirubin

Difference from baseline in laboratory parameter total Bilirubin (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

Interventionumol/L (Mean)
Volasertib (BI 6727)4.7

Laboratory Investigation: White Blood Cell Count

Difference from baseline in laboratory parameter white blood cell count (NCT01023958)
Timeframe: Baseline and last value on treatment (up to 2 years)

Intervention10^9 cells/L (Mean)
Volasertib (BI 6727)-1.8

Objective Tumour Response According to RECIST Criteria

Objective tumor response, defined as complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. (NCT01023958)
Timeframe: From first drug administration until end of study, up to 2 years

InterventionPercentage of participants (Number)
Volasertib (BI 6727)14.0

Occurrence of Unacceptable Toxicity

Occurrence of unacceptable toxicity is defined by CTCAE as as drug related CTCAE Grade 3 or greater non-hematological toxicity (except emesis or diarrhea responding to supportive treatment); drug-related CTCAE Grade 4 neutropenia for seven or more days and / or complicated by infection; or drug-related CTCAE Grade 4 thrombocytopenia. (NCT01023958)
Timeframe: From first drug administration up to 21 days after final administration, up to 2 years

InterventionPercentage of participants (Number)
Volasertib (BI 6727)30

Overall Survival

"Overall survival (OS) is the time from first infusion to death. Patients who were alive at the time of analysis or lost to follow-up were censored at the last follow-up date when they were known to be alive.~Overall survival was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals." (NCT01023958)
Timeframe: Time from first infusion to death, up to 2 years

InterventionMonths (Median)
Volasertib (BI 6727)8.5

Progression-free Survival

"Progression-free survival (PFS) is the time from first treatment to the occurrence of tumor progression or death, whichever occurs first. Disease progression is defined according to the RECIST guideline but also includes the investigators' assessment which may, in some cases, include only clinical progression (deterioration of general health status per investigator). PFS was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals.~Patients without evidence of disease progression were to be censored at the last image date." (NCT01023958)
Timeframe: Time from first treatment to the occurrence of tumor progression or death, up to 2 years

InterventionWeeks (Median)
Volasertib (BI 6727)6.1

t1/2 of Volasertib

Terminal half-life (t1/2) of volasertib (NCT01023958)
Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

Interventionhours (Geometric Mean)
Volasertib (BI 6727)150

Tmax of Volasertib

Time from dosing to maximum measured concentration (Tmax) of volasertib (NCT01023958)
Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

InterventionHours (Median)
Volasertib (BI 6727)2.03

Vss of Volasertib

Apparent volume of distribution at steady state following intravascular administration (Vss) of volasertib (NCT01023958)
Timeframe: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

InterventionLitres (Geometric Mean)
Volasertib (BI 6727)7470

Occurrence and Intensity of AE's Graded According to CTCAE

"Occurrence and intensity of adverse events (AEs) graded according to Common Toxicity Criteria of Adverse Events (CTCAE).~The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE)." (NCT01023958)
Timeframe: From first drug administration until end of study, up to 2 years

InterventionPercentage of participants (Number)
Grade 1Grade 2Grade 3Grade 4Grade 5
Volasertib (BI 6727)8.028.036.020.06.0

Number of Participants With Dose Limiting Toxicities (DLT)

MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, <500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever >38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2. (NCT01206816)
Timeframe: 22 Days

Interventionparticipants (Number)
Volasertib150 mg+Afatinib 30 mg (Schedule A)0
Volasertib 225 mg+Afatinib 30 mg (Schedule A)0
Volasertib 300 mg+Afatinib 30 mg (Schedule A)3
Volasertib 300 mg+Afatinib 40 mg (Schedule A)2
Volasertib 300 mg+Afatinib 50 mg (Schedule B)0
Volasertib 300 mg+Afatinib 70 mg (Schedule B)5
Volasertib 300 mg+Afatinib 90 mg (Schedule B)2

Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0

Number of patients with investigator defined drug-related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria v 3.0 (NCT01206816)
Timeframe: After the first drug administration until 28 days after the last drug administration, up to 413 days.

Interventionparticipants (Number)
Volasertib150 mg+Afatinib 30 mg (Schedule A)3
Volasertib 225 mg+Afatinib 30 mg (Schedule A)3
Volasertib 300 mg+Afatinib 30 mg (Schedule A)18
Volasertib 300 mg+Afatinib 40 mg (Schedule A)3
Volasertib 300 mg+Afatinib 50 mg (Schedule B)3
Volasertib 300 mg+Afatinib 70 mg (Schedule B)19
Volasertib 300 mg+Afatinib 90 mg (Schedule B)6

Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.

"Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The 3 + 3 design with de-escalation for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days." (NCT01206816)
Timeframe: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)

,
Interventionmg (Number)
VolasertibAfatinib
Volasertib in Combination With Afatinib (Schedule A)30030
Volasertib in Combination With Afatinib (Schedule B)30070

Number of Patients With Best Overall Response.

"Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response, partial response, stable disease, progressive disease or not evaluable.~As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression." (NCT01206816)
Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

,,,,,,
Interventionparticipants (Number)
Complete responsePartial responseStable diseaseProgressive diseaseNot evaluableUnknown
Volasertib 225 mg+Afatinib 30 mg (Schedule A)000300
Volasertib 300 mg+Afatinib 30 mg (Schedule A)018812
Volasertib 300 mg+Afatinib 40 mg (Schedule A)000300
Volasertib 300 mg+Afatinib 50 mg (Schedule B)001200
Volasertib 300 mg+Afatinib 70 mg (Schedule B)0051004
Volasertib 300 mg+Afatinib 90 mg (Schedule B)002400
Volasertib150 mg+Afatinib 30 mg (Schedule A)010200

Number of Patients With Disease Control

"Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Patients who had a best overall tumour response of complete response (CR), partial response (PR) or stable disease (SD) were assessed to show disease control.~As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression." (NCT01206816)
Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

,,,,,,
Interventionparticipants (Number)
YESNOUnknown
Volasertib 225 mg+Afatinib 30 mg (Schedule A)030
Volasertib 300 mg+Afatinib 30 mg (Schedule A)992
Volasertib 300 mg+Afatinib 40 mg (Schedule A)030
Volasertib 300 mg+Afatinib 50 mg (Schedule B)120
Volasertib 300 mg+Afatinib 70 mg (Schedule B)5104
Volasertib 300 mg+Afatinib 90 mg (Schedule B)240
Volasertib150 mg+Afatinib 30 mg (Schedule A)120

Number of Patients With Objective Response (OR)

"Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR).~As Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions." (NCT01206816)
Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

,,,,,,
Interventionparticipants (Number)
YesNoUnknown
Volasertib 225 mg+Afatinib 30 mg (Schedule A)030
Volasertib 300 mg+Afatinib 30 mg (Schedule A)1172
Volasertib 300 mg+Afatinib 40 mg (Schedule A)030
Volasertib 300 mg+Afatinib 50 mg (Schedule B)030
Volasertib 300 mg+Afatinib 70 mg (Schedule B)0154
Volasertib 300 mg+Afatinib 90 mg (Schedule B)060
Volasertib150 mg+Afatinib 30 mg (Schedule A)120

Trials

3 trials available for pteridines and Metastase

ArticleYear
Comprehensive Biomarker Analyses in Patients with Advanced or Metastatic Non-Small Cell Lung Cancer Prospectively Treated with the Polo-Like Kinase 1 Inhibitor BI2536.
    Oncology research and treatment, 2017, Volume: 40, Issue:7-8

    Topics: Antimitotic Agents; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cohort Studies; Disease Progr

2017
An open-label, single-arm, phase 2 trial of the Polo-like kinase inhibitor volasertib (BI 6727) in patients with locally advanced or metastatic urothelial cancer.
    Cancer, 2014, Apr-01, Volume: 120, Issue:7

    Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Disease-Free Survival; Female; Humans; Male; Middle

2014
A phase I study of volasertib combined with afatinib, in advanced solid tumors.
    Cancer chemotherapy and pharmacology, 2015, Volume: 76, Issue:4

    Topics: Administration, Oral; Adult; Afatinib; Aged; Antineoplastic Combined Chemotherapy Protocols; Cohort

2015

Other Studies

4 other studies available for pteridines and Metastase

ArticleYear
BCL-2 hypermethylation is a potential biomarker of sensitivity to antimitotic chemotherapy in endocrine-resistant breast cancer.
    Molecular cancer therapeutics, 2013, Volume: 12, Issue:9

    Topics: Antimitotic Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis

2013
Ribosomal s6 protein kinase 4: a prognostic factor for renal cell carcinoma.
    British journal of cancer, 2013, Sep-03, Volume: 109, Issue:5

    Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Butadienes; Carcinoma, Renal Cell; Cell Cycle; Cell Line

2013
Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression.
    Cancer discovery, 2016, Volume: 6, Issue:8

    Topics: Animals; Antineoplastic Agents; Biomarkers; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cell Mov

2016
Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2006, Jul-15, Volume: 12, Issue:14 Pt 1

    Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma; Cell Proliferation; Disease Progression; Epith

2006