tirapazamine, carboplatin, and paclitaxel in treating patients with advanced malignant solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

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 combining tirapazamine, carboplatin, and paclitaxel in treating patients who have advanced malignant solid tumors.

objectives: * determine the maximum tolerated dose of tirapazamine in combination with carboplatin and paclitaxel in patients with advanced solid tumors who have or have not received prior chemotherapy. * assess the toxicity and preliminary efficacy of this regimen in these patients. * determine the pharmacokinetic profile of this regimen in these patients. * investigate potential predictors of response by studying patient tissue specimens after receiving this regimen. outline: this is a dose-escalation study of tirapazamine. patients are stratified according to prior chemotherapy status (previously untreated vs previously treated). patients receive tirapazamine iv over 2 hours, paclitaxel iv over 3 hours, and carboplatin iv over 30 minutes. treatment continues every 21 days for a maximum of 8 courses in the absence of unacceptable toxicity or disease progression. some patients may continue therapy in the absence of unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of tirapazamine until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. an additional 12 patients in the previously untreated stratum are treated at the mtd. patients are followed indefinitely. projected accrual: a total of 36-68 patients (18-34 per stratum) will be accrued for this study within 12-18 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed advanced or metastatic malignant solid tumor not curable by resection or other standard therapy * no symptomatic brain metastases * brain metastases allowed provided controlled with surgical excision and/or radiotherapy patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * at least 3 months hematopoietic: * wbc at least 3,000/mm3 * absolute neutrophil count at least 1,000/mm3 * platelet count at least 100,000/mm3 hepatic: * bilirubin no greater than 1.5 mg/dl * sgot no greater than 2 times upper limit of normal renal: * creatinine normal * creatinine clearance at least 60 ml/min cardiovascular: * no new york heart association class iii or iv congestive heart failure other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 3 months after study * no history of allergic reactions to appropriate diuretics or antiemetics administered in conjunction with protocol chemotherapy (e.g., 5-ht3 antagonists) * no other concurrent uncontrolled illness that would preclude study therapy * no medical, social, or psychological factors that would preclude study therapy * no clinically significant hearing loss prior concurrent therapy: biologic therapy: * not specified chemotherapy: * at least 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) and recovered * no more than 2 prior chemotherapy regimens * no prior combination paclitaxel and carboplatin endocrine therapy: * not specified radiotherapy: * see disease characteristics * at least 4 weeks since prior radiotherapy and recovered * no concurrent radiotherapy surgery: * see disease characteristics * recovered from prior surgery other: * at least 30 days since other prior investigational drugs * no other concurrent anticancer therapy * no other concurrent investigational agents

Keywords: unspecified adult solid tumor, protocol specific