Clinical trial NCT00002774: Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer
Official title: Randomized Phase 2 Trial of Tirapazamine and the Role of Tumor Hypoxia in Advanced Squamous Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN)
Keywords: stage III
stage IV
recurrent
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-06
Enrollment: 63
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: DISEASE CHARACTERISTICS:

Biopsy proven squamous cell carcinoma of the following head and neck sites:

Hypopharynx Oral cavity Larynx Oropharynx Nasal cavity Unknown primary Paranasal sinus

Histologically proven poorly-differentiated carcinoma of the following head and neck sites:

Hypopharynx Oral cavity Larynx Oropharynx Nasal cavity Paranasal sinus Stage III/IV (T0-4 N1-3 M0-2) disease

PATIENT CHARACTERISTICS:

WBC at least 3,000/mm3 Bilirubin no greater than 2.0 mg/dL AST no greater than 100 U/L Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 60 mL/min (patients in Group N2-N3) No second malignancy within 5 years except curatively treated nonmelanomatous skin carcinoma No prior RT or chemotherapy, except prior radiotherapy to primary tumor allowed Not pregnant or nursing. Negative pregnancy test required Effective contraception required of fertile women Subjects with unknown primary cancers who had metastatic cervical lymph nodes are eligible Signed informed consent previously approved by the Institutional Review Board.

Primary outcomes:
measure: Complete response rate (CRR)
timeFrame: 12 weeks
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 years
measure: Cause-specific survival (CSS)
timeFrame: 5 years
measure: Rate of freedom from recurrence (FFR)
timeFrame: 5 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center - Palo Alto
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Stanford University
name: Harlan A. Pinto, MD
role: STUDY_CHAIR
References:
citation: Le QT, Taira A, Budenz S, Jo Dorie M, Goffinet DR, Fee WE, Goode R, Bloch D, Koong A, Martin Brown J, Pinto HA. Mature results from a randomized Phase II trial of cisplatin plus 5-fluorouracil and radiotherapy with or without tirapazamine in patients with resectable Stage IV head and neck squamous cell carcinomas. Cancer. 2006 May 1;106(9):1940-9. doi: 10.1002/cncr.21785.