Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer.
PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas|
- Disease-free survival (DFS) [ Time Frame: From randomization to date of failure (local, regional or distant progression or death) or last follow-up. Analysis occurs after 434 failures have been reported. ]
- Overall survival (OS) [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after 434 failures have been reported. ]
- Local-regional control (LRC) [ Time Frame: From randomization to date of failure (local or regional progression) or distant progression or death or last follow-up. Analysis occurs after 434 failures have been reported. ]
- Mucositis toxicity ≥ grade 3 [ Time Frame: From start of treatment to last follow-up ]
- Other toxicity ≥ grade 3 [ Time Frame: From start of treatment to last follow-up ]
- Protocol treatment delivery [ Time Frame: From start of treatment to end of treatment ]
- Death ≤ 30 days after discontinuation of protocol treatment [ Time Frame: From start of treatment to 30 days after the end of treatment ]
- Quality of life as measured by Performance Status Scale for Head and Neck Cancer and the European Quality of Life questionnaire (EQ-5D) [ Time Frame: From randomization to 5 years ]
- Quality of life as measured by Functional Assessment of Cancer Therapy-General version [ Time Frame: From randomization to 5 years ]
- Correlation of expression of epidermal growth factor receptor or its down-stream molecules (e.g., MAPK, AKT, Stat-3, PKC) with DFS, OS, and LRC [ Time Frame: From randomization to date of death or last follow-up ]Correlation of expression of epidermal growth factor receptor or its down-stream molecules (e.g., mitogen-activated protein kinase (MAPK), serine/threonine-specific protein kinase (AKT), Stat-3, PKC) with DFS, OS, and LRC
- Correlation of pre-treatment positron emission tomography (PET)/CT scan findings with DFS, OS, and LRC [ Time Frame: From randomization to date of death or last follow-up ]
- Correlation of post-treatment PET/CT scan findings with pathologic nodal complete response and nodal relapse rate at 2 years in clinical N2-3 patients [ Time Frame: From randomization to 2 years ]
|Study Start Date:||November 2005|
|Primary Completion Date:||January 2011 (Final data collection date for primary outcome measure)|
Active Comparator: Arm I
Patients receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.
Experimental: Arm II
Patients receive cetuximab IV over 1-2 hours once in weeks 0-7 and cisplatin as in arm I.
Given IVDrug: cisplatin
- Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve disease-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx.
- Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients.
- Correlate the expression of epidermal growth factor receptor (EGFR) and its down-stream molecules with outcome in patients participating in this component of the trial.
- Correlate pre-treatment PET scan findings with disease-free survival, overall survival, and local-regional control in patients participating in this component of the trial.
- Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial.
OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo either 3D-conformal radiotherapy or IMRT once or twice a day, 5 or 6 days a week, for 6 weeks. Patients also receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.
- Arm II: Patients receive cetuximab IV over 1-2 hours once in weeks 0-7. Beginning in week 1, patients also undergo radiotherapy and receive cisplatin as in arm I.
In both arms, patients with persistent nodal disease (any stage) (i.e., a residual palpable or radiographic abnormality) undergo neck dissection* approximately 9-10 weeks after completion of treatment.
NOTE: *A neck dissection is optional for patients with multiple lymph nodes or lymph nodes > 3 cm in diameter who achieve a complete clinical and radiographic response in the neck.
Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years.
After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.
PROJECTED ACCRUAL: Approximately 720 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00265941
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|Principal Investigator:||David Rosenthal, MD||M.D. Anderson Cancer Center|
|Study Chair:||Phuc Felix Nguyen-Tan, MD||CHUM Hospital Notre Dame|