Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific
Brief 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.
Detailed description
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.
Interventions
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed