Randomized Phase 2 Trial of Tirapazamine and the Role of Tumor Hypoxia in Advanced Squamous Head and Neck Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Stanford University
- Enrollment
- 63
- Locations
- 2
- Primary Endpoint
- Complete response rate (CRR)
Study Overview
Brief Summary
PURPOSE: Randomized phase 2 trial to compare the effectiveness of chemo-radiation therapy (RT + cisplatin + 5-FU) with or without tirapazamine for the treatment of patients with stage III or IV squamous cell carcinomas of the head and neck cancer (SCCHN).
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. Radiation therapy uses high-energy x-rays to damage tumor cells.
Tirapazamine may increase the effectiveness of chemotherapy and radiation therapy by making tumor cells more sensitive to therapy.
Detailed Description
Subjects were stratified according to pO2 values (high vs low), and randomized to 1 of 2 treatment arms, differing by the addition of tirapazamine to the therapeutic regimen. Treatment consists of two 21-day cycles of induction chemotherapy, followed by radiotherapy (RT).
Induction chemotherapy was cisplatin 100 mg/m2 per day administered over 4 hours on Study Days 1 and 22 (ie, 1st day of both induction cycles) with continuous infusion (CI) 5-FU at a dose of 1000 mg/m2 per day for 120 hours per cycle starting on Study Days 1 and 22 (ie, days 1 to 5 of both induction cycles).
Patients who achieve at least partial response proceeded to chemoradiotherapy (CRT) consisting of localized RT + cisplatin IV + 5-FU +/- tirapazamine. Location of RT was based on whether the site had a CR or PR. Radiotherapy began on day 43 (week 1), and continued for 5.5 weeks. Subjects with no response or progressive disease proceeded to salvage surgery.
A total of 63 patients were accrued for this study over approximately 5 years. 1 subject withdrew consent prior to treatment for personal reasons.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 17 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Tirapazamine + cisplatin + 5-FU
2 cycles of induction chemotherapy (tirapazamine, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (tirapazamine, cisplatin, and 5-FU)
Intervention: Tirapazamine (Drug)
Tirapazamine + cisplatin + 5-FU
2 cycles of induction chemotherapy (tirapazamine, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (tirapazamine, cisplatin, and 5-FU)
Intervention: Cisplatin (Drug)
Tirapazamine + cisplatin + 5-FU
2 cycles of induction chemotherapy (tirapazamine, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (tirapazamine, cisplatin, and 5-FU)
Intervention: 5-fluorouracil (Drug)
Tirapazamine + cisplatin + 5-FU
2 cycles of induction chemotherapy (tirapazamine, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (tirapazamine, cisplatin, and 5-FU)
Intervention: Radiotherapy (RT) (Radiation)
Cisplatin + 5-FU
2 cycles of induction chemotherapy (cisplatin + 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (cisplatin + 5-FU)
Intervention: Cisplatin (Drug)
Cisplatin + 5-FU
2 cycles of induction chemotherapy (cisplatin + 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (cisplatin + 5-FU)
Intervention: 5-fluorouracil (Drug)
Cisplatin + 5-FU
2 cycles of induction chemotherapy (cisplatin + 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (cisplatin + 5-FU)
Intervention: Radiotherapy (RT) (Radiation)
Outcomes
Primary Outcomes
Complete response rate (CRR)
Time Frame: 12 weeks
Compare the CRR following CRT with or without tirapazamine in patients with squamous cell carcinoma of the head and neck.
Secondary Outcomes
- Cause-specific survival (CSS)(5 years)
- Overall survival (OS)(5 years)
- Rate of freedom from recurrence (FFR)(5 years)