Oxaliplatin in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I/II Trial of Oxaliplatin as Neoadjuvant Treatment in Adults With Newly Diagnosed Glioblastoma Multiforme

Conditions
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Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

Intervention / Treatment
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* Drug: oxaliplatin
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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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 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No serious concurrent infection or medical illness that would jeopardize ability to receive protocol chemotherapy with reasonable safety No other prior malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer No grade 2 or greater pre-existing sensory neuropathy No history of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol chemotherapy Mini mental score at least 15 No prior immunotherapy for glioblastoma multiforme No prior biologic therapy for glioblastoma multiforme, including: Immunotoxins Immunoconjugates Antiangiogenesis compounds Antisense Peptide receptor antagonists Interferons Interleukins Tumor infiltrating lymphocytes Lymphokine activated killer cells Gene therapy No concurrent filgrastim (G-CSF) No prior chemotherapy for glioblastoma multiforme No prior hormonal therapy for glioblastoma multiforme Prior glucocorticoid therapy for glioblastoma multiforme allowed Must be maintained on a stable (lowest required dose) corticosteroid regimen for at least 5 days before and during study No concurrent dexamethasone as an antiemetic No prior radiotherapy for glioblastoma multiforme Recovered from immediate postoperative period At least 10 days since prior anticonvulsant drug that induces hepatic metabolic enzymes No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (oxaliplatin)<br>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. | Drug: oxaliplatin<br>* Given IV<br>* Other names: L-OHP;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |  | 14 days | 
| DLT is defined as grade 3 or 4 nonhematological toxicities or hematological toxicities as assessed by CTC version 2.0 (Phase I) |  | 14 days | 
| Pharmacokinetics of oxaliplatin (Phase I) |  | At baseline, at immediately post infusion, at 2, 4, 22, and 24 hours (of course 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (Phase II) |  | Up to 7 years | 
| Duration of survival (Phase II) | Estimated with 95% confidence intervals. | Up to 7 years | 
| Frequency of toxicity as assessed by CTC version 2.0 (Phase II) | The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals. | Up to 7 years after completion of study treatment |