carboplatin plus irinotecan in treating patients with glioblastoma multiforme

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. combining more than one drug may kill more tumor cells. purpose: phase ii trial to study the effectiveness of combining carboplatin with irinotecan in treating patients who have glioblastoma multiforme.

objectives: * determine the maximum tolerated dose (mtd) of carboplatin and irinotecan in patients with glioblastoma multiforme. (phase i closed to accrual as of 6/24/02) * determine the toxic effects of this regimen in these patients. * determine the objective response in patients treated with the established mtd of this regimen. * determine time to tumor progression and survival of patients treated with this regimen. outline: this is a dose-escalation study. patients in the phase ii portion of the study are stratified according to age (under 60 vs 60 and over), ecog performance status (0-1 vs 2), and extent of resection (total vs subtotal). (phase i closed to accrual as of 6/24/02) within 4 weeks of surgery, patients receive carboplatin iv over 30 minutes followed by irinotecan iv over 90 minutes on day 1. treatment repeats every 4 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of carboplatin and irinotecan until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. once the mtd is determined, additional patients are accrued to receive carboplatin and irinotecan at the recommended phase ii dose. (phase i closed to accrual as of 6/24/02) after chemotherapy, all patients undergo radiotherapy. patients are followed for 30 days. projected accrual: a total of 24-107 patients (3-54 for phase i and 21-53 for phase ii) will be accrued for this study. (phase i closed to accrual as of 6/24/02)

Eligibility criteria:
disease characteristics: * histologically confirmed glioblastoma multiforme * measurable disease * no cns metastases or carcinomatous meningitis patient characteristics: age: * 18 and over performance status: * ecog 0-2 or * karnofsky 70-100% life expectancy: * at least 12 weeks hematopoietic: * granulocyte count greater than 1,500/mm\^3 * platelet count greater than 100,000/mm\^3 * hemoglobin at least 9.0 g/dl hepatic: * bilirubin no greater than 1.5 mg/dl * sgot no greater than 3 times upper limit of normal (uln) (5 times uln if liver involvement) * no known gilbert's syndrome renal: * creatinine no greater than 1.5 mg/dl cardiovascular: * no myocardial infarction within the past 6 months * no congestive heart failure requiring therapy other: * hiv negative * no active or uncontrolled infection * no psychiatric disorder that would preclude study * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no uncontrolled diabetes mellitus (i.e., random blood sugar of 200 mg or more) * no other severe disease that would preclude study * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * no prior immunotherapy or biologic therapy * no concurrent sargramostim (gm-csf) * no concurrent filgrastim (g-csf) with course 1 * no concurrent immunotherapy chemotherapy: * no prior chemotherapy * no other concurrent chemotherapy endocrine therapy: * must have maintained a stable or decreasing dose of corticosteroids for 2 weeks prior to study * concurrent corticosteroids for cerebral edema allowed * no concurrent anticancer hormonal therapy radiotherapy: * no prior radiotherapy * no concurrent radiotherapy surgery: * at least 2 weeks since prior surgery other: * no other concurrent investigational agent or participation on any other clinical study * no concurrent immunosuppressive drugs * no concurrent phenobarbital or valproic acid * no concurrent anticonvulsants except carbamazepine or gabapentin * no concurrent prochlorperazine on day of irinotecan treatment

Keywords: adult glioblastoma adult giant cell glioblastoma adult gliosarcoma