Phase I/II Trial of R115777 in Patients With Recurrent Malignant Glioma

Inclusion Criteria

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