RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining tipifarnib with radiation therapy may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining tipifarnib with radiation therapy in treating patients who have newly diagnosed glioblastoma multiforme.

Condition	Treatment or Intervention	Phase
adult glioblastoma multiforme	Drug: tipifarnib  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the progression-free and overall survival of patients with newly diagnosed glioblastoma multiforme treated with tipifarnib and radiotherapy.
• Determine the response rate of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive oral tipifarnib twice daily for 3 weeks. Treatment repeats every 4 weeks for up to 3 courses.
• Radiotherapy: Within 14 days after the completion of induction therapy, patients undergo radiotherapy daily, 5 days a week, for 6 weeks.
• Maintenance therapy: Two weeks after the completion of radiotherapy, patients receive additional tipifarnib as in induction therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A minimum of 54 patients will be accrued for this study within 11-14 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial grade IV astrocytoma
• Glioblastoma multiforme
• Measurable and contrast-enhancing tumor on the postoperative MRI/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
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• AST/ALT no greater than 4 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Mini-mental state exam score at least 15
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
• No serious concurrent infection that would preclude study therapy
• No other medical illness that would preclude study therapy

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for brain tumor
• No prior biologic therapy for brain tumor, including any of the following:
• Immunotoxins
• Immunoconjugates
• Antisense therapy
• Peptide receptor antagonists
• Interferons
• Interleukins
• Tumor-infiltrating lymphocytes
• Lymphokine-activated killer cell therapy
• Gene therapy

Chemotherapy

• No prior chemotherapy for brain tumor
• No prior polifeprosan 20 with carmustine implant (Gliadel wafer)

Endocrine therapy

• No prior hormonal therapy (except glucocorticoids) for brain tumor
• Must be maintained on a stable corticosteroid regimen prior to study entry

Radiotherapy

• No prior radiotherapy for brain tumor

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• At least 10 days since prior hepatic metabolic enzyme-inducing anticonvulsant drugs, including the following:
• Phenytoin
• Carbamazepine
• Phenobarbital
• Primidone
• Oxcarbazepine
• No other concurrent investigational agents

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Massachusetts
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States
Michigan
      Josephine Ford Cancer Center at Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1030,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
Pennsylvania
      Abramson Cancer Center at University of Pennsylvania Medical Center, Philadelphia,  Pennsylvania,  19104-4283,  United States

Study chairs or principal investigators

Robert A. Lustig, MD,  Study Chair,  University of Pennsylvania Cancer Center   

Study ID Numbers:  CDR0000285732; NABTT-2200; JHOC-NABTT-2200
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  April 7, 2003
ClinicalTrials.gov Identifier:  NCT00058097
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08