Phase I Dose Escalation Study of Tirapazamine (NSC 130181) in Combination With Carboplatin and Paclitaxel in Advanced Malignant Solid Tumors
- 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
- 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.
Primary Purpose: Treatment
Stephen Shibata, MD
City of Hope Medical Center
United States: Federal Government
|USC/Norris Comprehensive Cancer Center and Hospital||Los Angeles, California 90033-0804|
|University of California Davis Cancer Center||Sacramento, California 95817|
|City of Hope Medical Center||Duarte, California 91010|
|City of Hope Medical Group||Pasadena, California 91105|