carmustine wafers plus irinotecan in treating patients with recurrent supratentorial high grade gliomas

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 i trial to study the effectiveness of carmustine wafers plus irinotecan in treating patients with recurrent supratentorial high grade gliomas.

objectives: * define the maximum tolerated dose of irinotecan given in combination with gliadel wafers (carmustine) in patients with recurrent glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma. * define the toxicity of irinotecan given in combination with gliadel wafers in these patients. outline: this is a dose escalation study. all patients undergo surgical resection. at the time of surgery, up to eight gliadel wafers (containing carmustine) are implanted in the resected tumor cavity. cohorts of 3 patients each receive escalating doses of irinotecan iv over 90 minutes once weekly within 3 weeks after gliadel wafer implantation. one course of treatment consists of 4 weeks of irinotecan and 2 weeks of rest. if 1 patient experiences dose limiting toxicity (dlt) at a dose level, an additional 3 patients are entered at that same dose level. if 2 patients experience dlt, the maximum tolerated dose (mtd) has been surpassed and a total of 6 patients are treated at the previous dose level. the mtd is defined as the highest dose in which no more than 1 of 6 patients experiences dlt. treatment continues for up to 12 courses in the absence of unacceptable toxicity and disease progression. patients are followed for at least 4 months. projected accrual: approximately 18 patients will be accrued into this study over 9 months.

Eligibility criteria:
disease characteristics: * histologically confirmed recurrent supratentorial glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma * must be able to undergo surgical resection * at least 1 bidimensionally measurable lesion documented on gd-mri within 72 hours after surgical implantation of gliadel wafers * not requiring immediate radiotherapy patient characteristics: age: * 18 and over performance status: * karnofsky 70-100% life expectancy: * greater than 12 weeks hematopoietic: * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 125,000/mm\^3 * hematocrit at least 29% hepatic: * bilirubin less than 1.5 times upper limit of normal (uln) * sgot or sgpt less than 2.5 times uln * alkaline phosphatase less than 2 times uln renal: * bun less than 1.5 times uln * creatinine less than 1.5 times uln neurological: * must be neurologically stable other: * hiv negative * no aids-related illness * no nonmalignant systemic disease that would make patient a poor medical risk * no acute infection requiring intravenous antibiotics * not pregnant or nursing * negative pregnancy test 24 hours prior to study * effective contraception required of all fertile patients prior concurrent therapy: biologic therapy: * not specified chemotherapy: * no prior irinotecan * at least 6 weeks since chemotherapy unless there is unequivocal evidence of tumor progression after chemotherapy endocrine therapy: * at least 1 week of nonincreasing dose of steroids prior to study radiotherapy: * at least 6 weeks since radiotherapy unless there is unequivocal evidence of tumor progression after radiotherapy * no concurrent radiotherapy surgery: * not specified

Keywords: recurrent adult brain tumor adult brain stem glioma adult glioblastoma adult anaplastic astrocytoma adult mixed glioma adult giant cell glioblastoma adult gliosarcoma