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

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.

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