Tipifarnib in Treating Patients With Recurrent or Progressive Malignant Glioma

DISEASE CHARACTERISTICS:

• Histologically confirmed intracranial primary malignant glioma
• Glioblastoma multiforme
• Anaplastic astrocytoma*
• Anaplastic oligodendroglioma*
• Anaplastic mixed oligodendroglioma*
• Malignant astrocytoma (not otherwise specified)* NOTE: *Closed to accrual effective 5/28/2002
• Progressive or recurrent disease confirmed by MRI or CT scan within the past 14 days
• Stable steroid dose for at least 5-7 days
• Confirmation of true progressive disease by PET scan, thallium scan, MR spectroscopy, or surgery if prior therapy included interstitial brachytherapy or stereotactic radiosurgery
• Failed prior radiotherapy
• Phase I (phase I completed effective 10/2/2001): No more than 2 prior chemotherapy or cytotoxic regimens, including 1 prior adjuvant therapy and 1 prior regimen for progressive or recurrent disease, or 2 prior regimens for progressive disease
• Phase II (phase II open only to patients requiring resection and who provide surgical tissue samples [effective 3/13/2003]): No more than 2 prior chemotherapy or cytotoxic regimens for relapsed disease following initial therapy (radiotherapy with or without chemotherapy)
• Prior surgical resection for relapsed disease with no anticancer therapy for up to 12 weeks followed by another surgical resection is considered 1 relapse
• Patients who received prior therapy for a low-grade glioma with a surgical diagnosis of a high-grade glioma are considered to be in first relapse

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• More than 8 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

• Bilirubin no greater than 2.5 times upper limit of normal (ULN)
• SGOT no greater than 2.5 times ULN

Renal:

• Creatinine less than 1.5 mg/dL

Cardiovascular:

• No uncontrolled high blood pressure
• No unstable angina
• No symptomatic congestive heart failure
• No myocardial infarction within the past 6 months
• No serious uncontrolled cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No severe nonmalignant systemic diseases or active infections
• No other severe concurrent disease that would preclude study therapy
• No allergy to azoles (e.g., ketoconazole, itraconazole, or voriconazole)
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior interferon
• No concurrent anticancer immunotherapy
• No concurrent routine prophylactic filgrastim (G-CSF) during first course of study
• No concurrent sargramostim (GM-CSF)

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, suramin, or mitomycin)
• At least 3 weeks since prior procarbazine
• At least 2 weeks since prior vincristine
• No other concurrent anticancer chemotherapy

Endocrine therapy:

• See Disease Characteristics
• At least 1 week since prior tamoxifen
• Concurrent corticosteroids allowed
• No concurrent anticancer hormonal therapy

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No concurrent anticancer radiotherapy

Surgery:

• See Disease Characteristics
• At least 3 weeks since prior resection and recovered
• Prior recent resection of recurrent or progressive tumor allowed

Other:

• Recovered from all prior therapy (excluding neurotoxicity or alopecia)
• Prior radiosensitizers allowed
• Concurrent H2 blockers and antacids allowed provided taken at least 2 hours before and after tipifarnib
• No concurrent proton pump inhibitors (e.g., omeprazole or lansoprazole)
• No other concurrent medication that would preclude study therapy (e.g., immunosuppressive agents)
• No other concurrent anticancer therapy
• No other concurrent investigational drugs
• No concurrent participation in any other clinical study
• No other concurrent medications except analgesics, chronic treatments for concurrent medical conditions, or agents for life-threatening medical problems