Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer

NCT00002774 | Completed Phase 2

• 5 other identifiers: IRB-12503CA67166NCI-T94-0119OCDR0000064752SQL 72951
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 2

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.

Conditions

Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN)

Keywords

stage III; stage IV; recurrent

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  Compare the CRR following CRT with or without tirapazamine in patients with squamous cell carcinoma of the head and neck.

  12 weeks

Secondary Outcomes (3)

• Overall survival (OS)

  5 years

• Cause-specific survival (CSS)

  5 years

• Rate of freedom from recurrence (FFR)

  5 years

Study Arms (2)

Tirapazamine + cisplatin + 5-FU

EXPERIMENTAL

2 cycles of induction chemotherapy (tirapazamine, cisplatin, and 5-fluorouracil \[5-FU\]) followed by simultaneous chemoradiotherapy (tirapazamine, cisplatin, and 5-FU)

Drug: Tirapazamine; Drug: Cisplatin; Drug: 5-fluorouracil; Radiation: Radiotherapy (RT)

Cisplatin + 5-FU

ACTIVE COMPARATOR

2 cycles of induction chemotherapy (cisplatin + 5-fluorouracil \[5-FU\]) followed by simultaneous chemoradiotherapy (cisplatin + 5-FU)

Drug: Cisplatin; Drug: 5-fluorouracil; Radiation: Radiotherapy (RT)

Interventions

Tirapazamine DRUG

Tirapazamine is a benzotriazine with selective cytotoxicity for hypoxic cells. Under hypoxic conditions, it undergoes a 1-electron reduction to form a cytotoxic free radical that poisons topoisomerase II and causes DNA breaks, chromosomal aberrations, and cell death. Tirapazamine was administered on Days 1 and 22 prior to the administration of neoadjuvant cisplatin and on Days 43, 45, 47, 71, 73, and 75 within 1 or 2 hours prior to each simultaneous cisplatin dose. Tirapazamine dose was as follows: Level 1 - 300 mg/m2 during the induction phase and 160 mg/m2 during the simultaneous phase (n = 4) Level 2 - 330 mg/m2 during the induction phase and 260 mg/m2 during the simultaneous phase (n = 4) Level 3 - 300 mg/m2 during the induction phase and 220 mg/m2 during the simultaneous phase (n = 25)

Also known as: Tirazone, TPZ, SR 4233, 3-amino-1,4-benzotriazine-1-N-oxide, WIN 59074

Tirapazamine + cisplatin + 5-FU

Cisplatin DRUG

The simultaneous chemoradiotherapy (CRT) regimen included cisplatin 20 mg/m2 administered 3 times per week.

Also known as: Cisplatinum, Cis-diamminedichloroplatinum(II), CDDP

Cisplatin + 5-FU; Tirapazamine + cisplatin + 5-FU

5-fluorouracil DRUG

100 mg/m2 per day on Days 1 and 22, and continuous infusion (CI) 5-FU at a dose of 1000 mg/m2 per day for 120 hours per cycle starting on Days 1 and 22. The simultaneous chemoradiotherapy (CRT) regimen included continuous infusion (CI) 5-FU 600 mg/m2 per day for 96 hours per cycle in Weeks 1 and 5 of RT.

Also known as: 5-FU

Cisplatin + 5-FU; Tirapazamine + cisplatin + 5-FU

Radiotherapy (RT) RADIATION

During the CRT regimen, RT was given within 3 hrs of the tirapazamine infusion. The dose for the parallel opposed fields was 2 Gy/fraction/day given 5 dys/week up to a total dose of 66-70 Gy at the target lesion. The dose to the supraclavicular region was 50 Gy at a depth of 3 cm, delivered in 25 fractions. Supervoltage photons (≥4 megavolts) were used to treat both locations. After 50 Gy were delivered to the primary site and regional lymph nodes, all sites were reassessed for clinical response by physical exam, direct fiber optic evaluation, and radiographic imaging (CT or MRI). Subjects with a CR at both the primary site and the neck completed RT treatment to a total dose ≥66 Gy to the primary site and the involved lymph node(s). Subjects with a CR at the primary site but a partial response (PR) at the neck completed RT treatment to the primary site followed by neck dissection. Subjects with a PR at the primary site stopped radiation at 50 Gy and underwent salvage surgery.

Cisplatin + 5-FU; Tirapazamine + cisplatin + 5-FU

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Stanford University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Veterans Affairs Medical Center - Palo Alto

Palo Alto, California, 94304, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5408, United States

Location

Related Publications (1)

• 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.

  PMID: 16532436 RESULT

MeSH Terms

Conditions

Head and Neck Neoplasms; Recurrence

Interventions

Tirapazamine; Cisplatin; Fluorouracil; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Therapeutics

Study Officials

• Harlan A. Pinto, MD

  Stanford University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2000
• First Posted: April 6, 2004
• Study Start: June 1, 1996
• Primary Completion: June 1, 2000
• Study Completion: June 1, 2005
• Last Updated: June 20, 2014

Record last verified: 2014-06

Locations

US (2)