Phase I/II Trial of Oxaliplatin as Neoadjuvant Treatment in Adults With Newly Diagnosed Glioblastoma Multiforme
Overview
- Phase
- Phase 1
- Intervention
- oxaliplatin
- Conditions
- Adult Giant Cell Glioblastoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 59
- Locations
- 1
- Primary Endpoint
- Maximum-tolerated dose (MTD) defined as the dose level at which 2 out of 6 or the dose level below that at which >= 2 of 3 or > 2 of 6 patients experience dose-limiting toxicity (DLT) assessed by Common Toxicity Criteria (CTC) version 2.0 (Phase I)
- Status
- Terminated
- Last Updated
- 13 years ago
Overview
Brief Summary
This phase I/II trial is studying the side effects and best dose of oxaliplatin in treating patients with newly diagnosed glioblastoma multiforme. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing
Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose of oxaliplatin in patients with newly diagnosed glioblastoma multiforme who are receiving or not receiving anticonvulsants known to be metabolized by P450. II. Determine the dose-limiting toxicity and safety profile of this drug in this patient population. III. Assess the pharmacokinetics of this drug on this schedule and determine the effects of P450-inducing anticonvulsants on the pharmacokinetics in these patients. IV. Determine the radiographic response rate in patients treated with this drug. V. Determine survival and drug toxicity in these patients. OUTLINE: This is a phase I dose-escalation study of oxaliplatin followed by a phase II study. Patients are stratified according to whether concurrent anticonvulsant drugs induce P450 (yes vs modest/no or no drugs). Phase I: Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients (per stratum) receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients receive oxaliplatin as in phase I at the MTD determined in phase I. Patients are followed at 1 month, every 2 months until disease progression, and then monthly thereafter. PROJECTED ACCRUAL: Approximately 24 patients (12 per stratum) will be accrued for the phase I part of this study within 8-12 months. A total of 18-35 patients will be accrued for the phase II part of this study within 5-12 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed supratentorial grade IV astrocytoma
- •Glioblastoma multiforme
- •Subtotal resection or biopsy with measurable and contrast-enhancing disease on the postoperative, pretreatment MRI/CT scan
- •Performance status - Karnofsky 60-100%
- •Absolute neutrophil count at least 1,500/mm\^3
- •Platelet count at least 100,000/mm\^3
- •Hemoglobin at least 9.0 g/dL
- •Bilirubin normal
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (oxaliplatin)
Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.
Intervention: oxaliplatin
Treatment (oxaliplatin)
Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.
Intervention: pharmacological study
Outcomes
Primary Outcomes
Maximum-tolerated dose (MTD) defined as the dose level at which 2 out of 6 or the dose level below that at which >= 2 of 3 or > 2 of 6 patients experience dose-limiting toxicity (DLT) assessed by Common Toxicity Criteria (CTC) version 2.0 (Phase I)
Time Frame: 14 days
DLT is defined as grade 3 or 4 nonhematological toxicities or hematological toxicities as assessed by CTC version 2.0 (Phase I)
Time Frame: 14 days
Pharmacokinetics of oxaliplatin (Phase I)
Time Frame: At baseline, at immediately post infusion, at 2, 4, 22, and 24 hours (of course 1)
Secondary Outcomes
- Response rate (Phase II)(Up to 7 years)
- Duration of survival (Phase II)(Up to 7 years)
- Frequency of toxicity as assessed by CTC version 2.0 (Phase II)(Up to 7 years after completion of study treatment)