Radiation Therapy With or Without Cetuximab in Treating Patients With Stage III or Stage IV Cancer of the Oropharynx, Hypopharynx, or Larynx

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known if radiation therapy is more effective with or without cetuximab for cancer of the oropharynx, hypopharynx, or larynx. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without cetuximab in treating patients who have stage III or stage IV cancer of the oropharynx, hypopharynx, or larynx.

Detailed Description
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OBJECTIVES: Compare the rate of locoregional disease control maintained for 1 year in patients with advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx treated with radiotherapy with or without concurrent cetuximab. Compare the response rates, progression-free survival and overall survival rates, and quality of life in patients treated with these regimens. Compare acute and late toxicity of these regimens in these patients. Determine tumor epidermal growth factor receptor levels in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified by Karnofsky performance status (60-80% vs 90-100%), nodal stage (N0 vs N+), tumor stage (T1-3 vs T4), and radiotherapy schedule (concurrent boost vs once daily vs twice daily). Patients are randomized to 1 of 2 treatment arms: Arm I: Patients undergo radiotherapy beginning on day 1. Patients are assigned to 1 of 3 radiotherapy groups: Group 1: Patients undergo concurrent boost radiotherapy comprised of radiotherapy once daily 5 days a week for 3.5 weeks followed by radiotherapy twice daily 5 days a week for 2.5 weeks. Group 2: Patients undergo radiotherapy once daily 5 days a week for 7 weeks. Group 3: Patients undergo radiotherapy twice daily 5 days a week for 6-6.5 weeks. Arm II: Patients receive a test dose of cetuximab IV over 10 minutes on day 1. Patients who do not experience grade 4 anaphylactic reaction receive a loading dose of cetuximab IV over 2 hours beginning 30 minutes after completion of test dose. Patients receive maintenance cetuximab IV over 1 hour on day 8. Maintenance cetuximab repeats every week for 7 courses. Beginning on day 8, patients undergo radiotherapy as in arm I concurrently with maintenance cetuximab. There must be an hour interval between the completion of cetuximab infusion and the start of any radiotherapy. Patients with more than N1 neck disease at initial presentation undergo neck dissection 4-8 weeks after the completion of radiotherapy. Quality of life is assessed before initiation of study therapy, at 8 weeks, and then every 4 months for 1 year. Patients are followed at 8 weeks, every 4 months for 2 years, and then every 6 months for 3 years. PROJECTED ACCRUAL: Approximately 416 patients (208 per arm) will be accrued for this study within approximately 5 years.

Official Title
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Randomized Phase III Trial to Compare Radiation Therapy Alone With Radiation Therapy and Concomitant Anti-EGFr Antibody (C225) for Locally Advanced Squamous Cell Carcinomas of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: cetuximab
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx Stage III OR Stage IV without distant metastases Measurable disease Tumor tissue available for immunohistochemical assay of epidermal growth factor receptor expression PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 1 year Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT and SGPT no greater than 2 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 50 mL/min Calcium normal Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Medically able to withstand a course of definitive radiotherapy No medical or psychologic condition that would preclude informed consent or compliance No other malignancy within the past 3 years except basal cell skin cancer or preinvasive carcinoma of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: No prior cetuximab or other murine monoclonal antibody Chemotherapy: At least 3 years since prior systemic chemotherapy No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to head and neck No other concurrent radiotherapy Surgery: No prior surgery for indicator lesion except biopsy Study radiotherapy must not be a part of a postoperative regimen after primary surgical resection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm I<br>Patients undergo radiotherapy beginning on day 1. Patients are assigned to 1 of 3 radiotherapy groups: Group 1: Patients undergo concurrent boost radiotherapy comprised of radiotherapy once daily 5 days a week for 3.5 weeks followed by radiotherapy twice daily 5 days a week for 2.5 weeks. Group 2: Patients undergo radiotherapy once daily 5 days a week for 7 weeks. Group 3: Patients undergo radiotherapy twice daily 5 days a week for 6-6.5 weeks. | Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |
| Active Comparator: Arm II<br>Patients receive a test dose of cetuximab IV over 10 minutes on day 1. Patients who do not experience grade 4 anaphylactic reaction receive a loading dose of cetuximab IV over 2 hours beginning 30 minutes after completion of test dose. Patients receive maintenance cetuximab IV over 1 hour on day 8. Maintenance cetuximab repeats every week for 7 courses. Beginning on day 8, patients undergo radiotherapy as in arm I concurrently with maintenance cetuximab. There must be an hour interval between the completion of cetuximab infusion and the start of any radiotherapy. Radiotherapy groups remain the same as in Arm I: Group 1: Patients undergo concurrent boost radiotherapy comprised of radiotherapy once daily 5 days a week for 3.5 weeks followed by radiotherapy twice daily 5 days a week for 2.5 weeks. Group 2: Patients undergo radiotherapy once daily 5 days a week for 7 weeks. Group 3: Patients undergo radiotherapy twice daily 5 days a week for 6-6.5 weeks. | Biological: cetuximab<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx