temozolomide and Brain Stem Neoplasms

temozolomide has been researched along with Brain Stem Neoplasms in 38 studies

Brain Stem Neoplasms: Benign and malignant intra-axial tumors of the MESENCEPHALON; PONS; or MEDULLA OBLONGATA of the BRAIN STEM. Primary and metastatic neoplasms may occur in this location. Clinical features include ATAXIA, cranial neuropathies (see CRANIAL NERVE DISEASES), NAUSEA, hemiparesis (see HEMIPLEGIA), and quadriparesis. Primary brain stem neoplasms are more frequent in children. Histologic subtypes include GLIOMA; HEMANGIOBLASTOMA; GANGLIOGLIOMA; and EPENDYMOMA.

Research

Studies (38)

Authors

Clinical Trials (5)

Trial Overview

Trial Outcomes

Apparent Volume of Distribution (Vd/F) for Veliparib [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. (NCT01514201)
Timeframe: Up to day 4

Maximum Concentration of Veliparib (Cmax) on Day 1 (Measured in μM) [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. Cmax measures the highest concentration of drug. (NCT01514201)
Timeframe: Day 1

Maximum-tolerated Dose of Veliparib Defined as Highest Dose Level With Fewer Than 2 Dose Limiting Toxicities in 6 Patients as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)

The traditional 3+3 dose finding algorithm was used to estimate the maximum-tolerated dose of veliparib given concurrently with radiation therapy. The dose-limiting toxicity observation period was the first 10 weeks of therapy. Dose-limiting toxicities included any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with a few exceptions (see section 5.2.1.2 of the protocol document), any grade 2 non-hematologic toxicity that persisted for >7 days and considered medically significant that required treatment interruption; grade 3 or higher thrombocytopenia or grade 4 neutropenia; and any Veliparib related adverse event that led to a dose reduction or the permanent cessation of therapy. (NCT01514201)
Timeframe: 10 weeks

Mean Apparent Clearance (CL/F) for Veliparib [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. (NCT01514201)
Timeframe: Up to day 4

Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)

DLTs were defined as any of the following adverse events that were at least possibly attributable to Veliparib observed during the dose finding phase (the first 10 weeks of therapy). Hematologic dose limiting toxicities included grade 3 and higher thrombocytopenia or grade 4 neutropenia. Non-hematologic dose limiting toxicities included any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with some exceptions (e.g., nausea and vomiting of <5 days; fever or infection of <5 days; hypophosphatemia, hypokalemia, hypocalcemia or hypomagnesemia responsive to oral supplementation; elevation of transaminases that return to levels meeting eligibility criteria within 7 days), or any grade non-hematologic toxicity that persisted for >7 days and considered medically significant or sufficiently intolerable by patients that required treatment interruption. (NCT01514201)
Timeframe: 10 weeks

Overall Survival

Overall survival was defined as the interval from date on treatment to date of death from any cause or to date of last follow-up. Patients who had not failed (died) at the time of analyses were censored at their last date of contact. The method of Kaplan and Meier was used to estimate overall survival. The 3-year estimate with a 95% confidence interval is reported. (NCT01514201)
Timeframe: Time from initiation of therapy to the date of death from any cause or to the date patient was known to be alive for surviving patients, assessed to up to 3 years

Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)

Unacceptable toxicities during maintenance included events at least possibly attributable to Veliparib and temozolomide (TMZ) such as any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with some exceptions (e.g., grade 3 nausea/vomiting <5 days, grade 3 fever or infection <5 days), grade 3+ thrombocytopenia, grade 4 neutropenia, delay >14 days in starting subsequent cycle due to neutrophil <1,000/mm3 or platelet <100,000/mm3. Maintenance therapy was initiated with 25 mg/m2 Veliparib and 135 mg/m2 of TMZ, with the possibility to escalate TMZ to 175 mg/m2 and 200 mg/m2 in courses 2 and 3, respectively, if no unacceptable toxicities occurred following one course of treatment at each of the dose levels to be tested. Intra-patient dose escalation to a given dose (135, 175, or 200 mg/m2) was halted based on rules employed in 3+3 designs. This dose escalation was intended for all patients but was halted early, during the phase I portion, as it was not well tolerated. (NCT01514201)
Timeframe: 28 days per treatment cycle

Percentage of Participants With Significant Changes in Poly(ADP-ribose) Polymerase (PARP) Levels Post-Veliparib, as Measured in Peripheral Blood Monocytes (PBMCs)

Blood samples were collected from patients and assessed pre- and post-Veliparib to assess treatment-induced changes. A significant change in PBMC PARP level was arbitrarily defined as a >50% increase or decrease from the pre-treatment level, documented at week 6 and/or week 11 after starting protocol therapy. (NCT01514201)
Timeframe: Baseline and up to 11 weeks

Percentage of Patients With Pseudo Progression

For participants that showed possible tumor progression (pseudo progression) on magnetic resonance imaging (MRI) during the first 6 months of therapy, treating physicians had the option of allowing patients to remain on therapy and repeating the disease assessment in 4-6 weeks. If the repeat MRI at 4-6 weeks showed disease progression, the patient was noted to have true disease progression (and the progression date corresponded to that of the first MRI). If the repeat MRI at 4-6 weeks did not show disease progression, then the patient was noted to have pseudo progression. The percentage of patients observed to have experienced pseudo progression was provided with a 95% confidence interval. (NCT01514201)
Timeframe: Up to 6 months

Progression-free Survival (PFS)

PFS was defined as the interval from date of treatment initiation to date of first event (disease progression or relapse, second malignancy or death from any cause). Patients who had not failed at the time of analyses were censored at their last date of contact. The method of Kaplan and Meier was used to estimate PFS. A 3-year estimate with a 95% confidence interval is reported. (NCT01514201)
Timeframe: Time from initiation of treatment to the earliest date of failure (disease progression, death from any cause, or second malignancy), assessed up to 3 years

Terminal Half-life (t1/2) for Veliparib [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. (NCT01514201)
Timeframe: Up to day 4

Trough for Veliparib [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. (NCT01514201)
Timeframe: Up to day 4

Levels of Urinary Biomarkers

Urine samples were analyzed for a panel of biomarkers. Netrin-1 levels were determined by ELISA. Levels of matrix metalloproteinase 3 (MMP3) and basic fibroblast growth factor (bFGF) were analyzed using custom Luminex® screening assays. Tissue inhibitor of metalloproteinase 1 (TIMP1) levels were analyzed using a Luminex® performance assay. Protein concentrations are given in picograms per microgram (pg/μg), and were determined by dividing the concentration of the target protein in the sample (pg/mL) by the concentration of total protein in the sample (μg/mL) as a normalization measure. (NCT01514201)
Timeframe: Baseline to up to 3 years

Maximum Concentration of Veliparib (Cmax) on Days 1 and 4 (Measured in ng/mL) [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. Cmax measures the highest concentration of drug. (NCT01514201)
Timeframe: Up to day 4

Reviews

2 reviews available for temozolomide and Brain Stem Neoplasms

Trials

11 trials available for temozolomide and Brain Stem Neoplasms

Other Studies

25 other studies available for temozolomide and Brain Stem Neoplasms