Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically or cytologically confirmed glioblastoma multiforme.

• - Some oligodendroglial elements allowed provided they make up < 25% of the tumor.

• - Recurrent disease documented by MRI after prior radiotherapy.

• - At least 1 bidimensionally measurable target lesion ≥ 2 cm by MRI.

• - Undergone prior surgery for recurrent primary brain tumor more than 3 months before study entry.

• - Must have a clearly limited target lesion ≥ 2 cm OR evidence of progressive and measurable target lesion OR a second measurable target lesion outside the surgical area.

PATIENT CHARACTERISTICS: Age.

• - Over 18.

Performance status.

• - Karnofsky 70-100% Life expectancy.

• - Not specified.

Hematopoietic.

• - Absolute neutrophil count ≥ 1,500/mm^3.

• - Platelet count ≥ 100,000/mm ^3.

Hepatic.

• - AST and ALT < 2.5 times upper limit of normal (ULN) - Bilirubin < 1.5 times ULN.

Renal.

• - Creatinine < 1.5 times ULN.

Cardiovascular.

• - Clinically normal cardiac function.

• - No ischemic heart disease within the past 12 months.

• - No New York Heart Association grade III or IV cardiac insufficiency.

• - No unstable angina.

• - No arryhthmia.

Pulmonary.

• - DLCO > 70% of predicted (for patients randomized to receive erlotinib [arm I] or carmustine [arm II]) - No history of pulmonary disease that would affect pulmonary function including any of the following: - Chronic bronchopneumopathy.

• - Pleural effusion.

• - Interstitial pnuemonia.

• - Pulmonary lymphangitis.

Other.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception during and for 3 months after study participation.

• - No other malignancy except cone biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer.

• - No psychological, familial, sociological, or geographical factors that would preclude study compliance.

PRIOR CONCURRENT THERAPY: Biologic therapy.

• - No prior HER-targeted agents.

• - No concurrent growth factors for neutrophil count elevation.

• - No concurrent epoetin alfa.

Chemotherapy.

• - Prior adjuvant temozolomide allowed.

• - At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) - No more than 1 prior adjuvant chemotherapy regimen.

• - No prior chemotherapy for recurrent disease.

Endocrine therapy.

• - Must be on a stable or decreasing dose of corticosteroids for at least 2 weeks before study entry.

Radiotherapy.

• - See Disease Characteristics.

• - More than 3 months since prior radiotherapy to the brain.

• - No prior high-dose radiotherapy (> 65 Gy), stereotactic radiosurgery, or internal radiotherapy unless disease recurrence confirmed.

Surgery.

• - See Disease Characteristics.

Other.

• - No prior participation in experimental therapies.

• - No concurrent CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, troleandomycin, cimetidine, or grapefruit juice) - No concurrent warfarin or other coumarin derivatives.

• - Concurrent low-molecular weight heparin allowed.

- No other concurrent investigational drugs

OBJECTIVES: Primary.

• - Compare the therapeutic activity of erlotinib vs.#46;temozolomide or carmustine in patients with recurrent glioblastoma multiforme.

• - Compare 6-month progression-free survival in patients treated with these drugs.

Secondary.

• - Compare the safety of these drugs in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

• - Arm I: Patients receive oral erlotinib* once daily on day 1-28.

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: *Patients treated with enzyme inducing anti-epileptic drugs (EIAEDs) receive a higher dose of erlotinib than patients not receiving any anti-epileptic drugs or EIAEDs.

• - Arm II: Patients who have not received prior temozolomide are assigned to receive temozolomide.

Patients who have received prior temozolomide are assigned to receive carmustine. Patients receive 1 of the following treatment regimens:

• - Patients receive oral temozolomide* once daily on days 1-5.

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

• - Patients receive carmustine IV once daily on days 1-3.

Treatment repeats every 56 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. NOTE: *Chemotherapy-naïve patients receive a higher dose of temozolomide than patients who have received prior adjuvant chemotherapy. Patients are followed every 8 weeks until disease progression and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 100-110 patients (50-55 per treatment arm) will be accrued for this study.