A Phase I Study Of Tirapazamine In Combination With Radiation And Weekly Cisplatin In Patients With Locally Advanced Cervical Cancer
- Determine the maximum tolerated dose and the recommended phase II and III dose of
tirapazamine when combined with cisplatin and radiotherapy in patients with Stage
IB-IVA squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the
- Determine the safety and tolerability of this regimen in these patients.
- Determine failure-free survival of patients treated with this regimen.
- Determine overall survival of patients treated with this regimen.
- Determine time to locoregional failure in patients treated with this regimen.
- Determine patterns of failure for the site of first failure in patients treated with
- Determine the 12-week post-treatment complete response rate in patients treated with
OUTLINE: This is a multicenter, dose-escalation study of tirapazamine.
Patients receive tirapazamine IV over 2 hours on day 1 of weeks 1-5 and on days 3 and 5 of
weeks 1 and 2 (cohort 2 only), OR days 3 and 5 of weeks 1-4 (cohort 3 only). Patients also
receive cisplatin IV over 1 hour on day 1 of weeks 1-6. Patients concurrently undergo
external beam radiotherapy once daily on days 1-5 for 5-5.5 weeks. After completion of
chemoradiotherapy, patients undergo low-dose brachytherapy (up to 2 implants within an
8-week period) OR high-dose brachytherapy twice weekly for 5 treatments. Treatment continues
in the absence of disease progression or 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 3 or 2
of 6 patients experience dose-limiting toxicity. At least 10 patients are treated at the
Patients are followed at 2, 4, and 8 weeks, at 3 and 6 months, every 3 months for 2 years,
and then every 6 months for 2 years.
PROJECTED ACCRUAL: A total of 3-22 patients will be accrued for this study.
Primary Purpose: Treatment
Maximum tolerated dose of tirapazamine
Danny Rischin, MD
Peter MacCallum Cancer Centre, Australia
United States: Food and Drug Administration