Oxaliplatin in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Oxaliplatin in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
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
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.
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