Phase I/II Trial of Oxaliplatin as Neoadjuvant Treatment in Adults With Newly Diagnosed Glioblastoma Multiforme
18 Years
N/A
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
Trial Information
Phase I/II Trial of Oxaliplatin as Neoadjuvant Treatment in Adults With Newly Diagnosed Glioblastoma Multiforme
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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)
Outcome Time Frame:
14 days
Safety Issue:
Yes
Principal Investigator
Tracy Batchelor
Investigator Role:
Principal Investigator
Investigator Affiliation:
New Approaches to Brain Tumor Therapy Consortium
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02336
NCT ID:
NCT00005856
Start Date:
December 2000
Completion Date:
Related Keywords:
- Adult Giant Cell Glioblastoma
- Adult Glioblastoma
- Adult Gliosarcoma
- Glioblastoma
- Gliosarcoma
Name | Location |
|---|---|
| New Approaches to Brain Tumor Therapy Consortium | Baltimore, Maryland 21231-1000 |
