Clinical Trial Finder

Inclusion Criteria:

• - Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM) or gliosarcoma (GS) - Diagnosis will have been established by biopsy or resection within 4 weeks prior to registration.

• - Patients must not have received previous radiotherapy to the brain.

• - Patients must not have received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor; patients who received Gliadel wafers will be excluded; patients may have received or be receiving corticosteroids, non-EIAEDs, analgesics, and other drugs to treat symptoms or prevent complications.

• - Cranial MRI or contrast CT must have been performed within 21days of study entry; the use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement; if the surgical procedure was a resection, cranial MRI or contrast CT performed with 96 hours of resection is preferred but not required; patients without measurable or assessable disease are eligible.

• - Patients must have a plan to begin partial brain radiotherapy within 5-9 days after beginning R115777, and within 35 days (5 weeks) of the surgical procedure that established the diagnosis; radiotherapy must be given at the Radiation Oncology Department of the registering ABTC institution; radiotherapy must be given by external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned total dose to the tumor of 60.0 Gy; stereotactic radiosurgery and brachytherapy will not be allowed.

• - Patients must be willing to forego other drug therapy against the tumor while being treated with R115777 and temozolomide.

• - All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must sign an authorization for the release of their protected health information; patients must be registered with the Adult Brain Tumor Consortium Central Office (ABTC CO) prior to treatment with study drug.

• - Life expectancy > 8 weeks.

• - Patients must have a Karnofsky performance status of >= 60.

• - Patients must have adequate bone marrow function and the test must be performed within 14 days prior to registration; eligibility level for hemoglobin may be reached by transfusion.

• - WBC >= 3,000/µl.

• - ANC >= 1,500/mm^3.

• - Platelet count of >= 100,000/mm^3.

• - Hemoglobin >= 10 gm/dl.

• - Patients must have adequate liver function and the test must be performed within 14 days prior to registration.

• - SGOT < 2 times ULN.

• - Bilirubin < 2 times ULN.

• - Patients must have adequate renal function before starting therapy and the test must be performed within 14 days prior to registration.

• - Creatinine < 1.5 mg/dL.

• - Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.

• - Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.

• - This study was designed to include women and minorities, but was not designed to measure differences of intervention effects; males and females will be recruited with no preference to gender; no exclusion to this study will be based on race; minorities will actively be recruited to participate.

• - Patients must not have active infection.

• - Women must not be pregnant or Breast-feeding, and women with reproductive potential must practice adequate contraception; the anti-proliferative effects of the investigational agent may be detrimental to the developing fetus or nursing infant.

- Patients must not be on chronic coumadin therapy for prior medical problems (e.g. cardiac valve prophylaxis); this is due to a presumed interaction with coumadin and ZARNESTRA leading to a significant increase in INR; patients who develop or have recently developed a deep venous thrombosis or pulmonary embolism who are on or will take coumadin will be allowed to participate; however, the investigator should be prepared to monitor patients INR closely

PRIMARY OBJECTIVES:

• I. Establish MTD for R115777 in combination with Temozolomide with radiation in patients not on EIAEDs.

• II. To define the safety of R115777 in combination with Temozolomide with radiation in this patient population.

• III. To assess for evidence of antitumor activity in this patient population.

OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes [closed to accrual as of 3/15/05] vs.#46;no). COMBINATION THERAPY: Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Within 5-9 days after beginning tipifarnib, patients receive oral temozolomide once daily for 6 weeks and concurrently undergo partial brain radiotherapy daily 5 days a week for 6 weeks. After completion of radiotherapy, patients proceed to adjuvant therapy. Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD. ADJUVANT THERAPY: Patients continue to receive tipifarnib as above. With the initiation of the next planned course of tipifarnib, patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for 12 courses OR 1 year (whichever is longer) in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients with progressive disease are followed at 10 weeks and then every 4 months. Patients who complete therapy are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter until disease progression.

Arms

Experimental: Treatment (tipifarnib, temozolomide, radiation therapy)

See Detailed Description

Interventions

Drug: - tipifarnib

Given PO

Drug: - temozolomide

Given PO

Radiation: - radiation therapy

Undergo partial brain radiation therapy