Phase I Dose Escalation Study of Tirapazamine (NSC 130181) in Combination With Carboplatin and Paclitaxel in Advanced Malignant Solid Tumors
carboplatin
+ paclitaxel
+ tirapazamine
Treatment Study
Summary
Study start date: March 1, 2000
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.44 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.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
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 4 locations
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, United StatesCity of Hope Medical Group
Pasadena, United StatesUniversity of California Davis Cancer Center
Sacramento, United States