Efaproxiral Plus Carmustine in Treating Patients With Progressive or Recurrent Malignant Glioma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of efaproxiral when given with carmustine and to see how well they work in treating patients with progressive or recurrent malignant glioma.

Detailed Description
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OBJECTIVES: Evaluate the safety and tolerability of escalating doses of efaproxiral (RSR13) when administered concurrently with carmustine in patients with progressive or recurrent malignant glioma. Determine the maximum tolerated dose (MTD) of RSR13 when administered with carmustine in this patient population. Determine the pharmacokinetic profile of this regimen in these patients. Estimate the efficacy of this regimen at the MTD in these patients. OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of efaproxiral (RSR13). Patients receive RSR13 IV over 30 minutes followed 30 minutes later by carmustine IV over 1-2 hours on day 1. Treatment repeats every 6 weeks for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 6-12 patients receive escalating doses of RSR13 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 5 of 12 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with RSR13 and carmustine at the recommended phase II dose. Patients are followed at 6 weeks and then every 2 months thereafter. PROJECTED ACCRUAL: A maximum of 48 patients will be accrued for the phase I portion of this study. A maximum of 47 patients will be accrued for the phase II portion of this study.

Official Title
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A Phase I/II Study to Evaluate the Safety and Tolerance of Escalating Doses of RSR13 Administered With a Fixed Dose of BCNU Every Six Weeks in Patients With Recurrent Malignant Glioma

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: carmustine
* Drug: efaproxiral


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma that is progressive or recurrent after radiotherapy with or without chemotherapy Anaplastic astrocytoma Anaplastic oligodendroglioma Glioblastoma multiforme Prior low-grade glioma allowed provided progression has occurred after radiotherapy with or without chemotherapy and then high-grade glioma is found on biopsy Measurable disease by serial MRI or CT scan PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Hemoglobin at least 10 g/dL Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 2.0 mg/dL Alkaline phosphatase no greater than 3 times upper limit of normal (ULN) SGOT and SGPT no greater than 3 times ULN Renal: Creatinine no greater than 2.0 mg/dL Pulmonary: Resting oxygen saturation on room air at least 90% by pulse oximetry FVC, DLCO, and FEV_1 at least 50% of normal Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other serious concurrent medical illness that would preclude study compliance No other prior malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior investigational biologics Chemotherapy: See Disease Characteristics No prior nitrosoureas for glioma No more than 1 prior chemotherapy regimen At least 4 weeks since prior chemotherapy No prior efaproxiral Endocrine therapy: Concurrent corticosteroids (e.g., dexamethasone) allowed Radiotherapy: See Disease Characteristics At least 90 days since prior radiotherapy Surgery: Not specified Other: At least 3 weeks since other prior investigational drugs or devices

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
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carmustine|nan|
|Drug: efaproxiral|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability |  |  | 
| Maximum tolerated dose |  |  | 
| Pharmacokinetic profile |  |  | 
| Efficacy |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma