RANDOMIZED PHASE II TRIAL OF TIRAPAZAMINE AND THE ROLE OF TUMOR HYPOXIA IN ADVANCED SQUAMOUS HEAD AND NECK CANCER

Trial Information

RANDOMIZED PHASE II TRIAL OF TIRAPAZAMINE AND THE ROLE OF TUMOR HYPOXIA IN ADVANCED SQUAMOUS HEAD AND NECK CANCER

OBJECTIVES: I. Compare the complete response rate following radiotherapy with or without
tirapazamine (SR-4233) in patients with N1 squamous cell carcinoma of the head and neck. II.
Compare the complete response rate to induction chemotherapy with cisplatin (CDDP) and
fluorouracil (5-FU) with and without SR-4233 followed by concurrent CDDP/5-FU plus
radiotherapy with and without SR-4233 in patients with N2 or N3 squamous cell carcinoma of
the head and neck. III. Assess whether tumor hypoxia contributes to tumor resistance to
treatment by measuring oxygen tension in cervical lymph node metastases and correlating
these results with treatment response in both groups of patients.

OUTLINE: This is a randomized study. Patients are stratified according to pO2 values (high
vs low). Patients are randomized to one of two treatment arms. Arm I: Patients receive
induction chemotherapy consisting of fluorouracil IV continuously on days 1-5 and cisplatin
IV over 4 hours on day 1. Treatment is repeated every 21 days for 2 courses. Patients who
achieve at least partial response proceed to chemoradiotherapy consisting of cisplatin IV
over 30-60 minutes, three times a week, during weeks 1 and 5. Patients also receive
fluorouracil IV continuously for 4 days beginning on day 43 and again on day 71.
Radiotherapy begins on day 43 (week 1) for 5.5 weeks. Patients with no response or
progressive disease after induction chemotherapy proceed to salvage surgery. Arm II:
Patients receive induction chemotherapy as in arm I plus tirapazamine IV over 1.0-2.5 hours
prior to cisplatin. Patients proceed as in arm I. Those patients receiving chemoradiotherapy
also receive tirapazamine IV on the same days as cisplatin. Some patients receive further
radiotherapy and/or surgery. Patients are followed monthly for 1 year, every 2 months for 1
year, every 3 months for 1 year, every 6 months for 2 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study over approximately
5 years.