Randomized Phase II of TARCEVA™ (Erlotinib) Versus Temozolomide Or BCNU in Patients With Recurrent Glioblastoma Multiforme

Date de début de l'étude : 1 mai 2004

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