S0427, Combination Chemotherapy & RT in Treating Patients With Stage III or Stage IV Cancer of the Oropharynx

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known whether giving combination chemotherapy together with radiation therapy is more effective than giving cisplatin together with radiation therapy in treating cancer of the oropharynx. PURPOSE: This randomized phase III trial is studying combination chemotherapy and radiation therapy to see how well they work compared to cisplatin and radiation therapy in treating patients with stage III or stage IV cancer of the oropharynx.

Detailed Description
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OBJECTIVES: Primary Compare the overall survival of patients with previously untreated stage III or IV squamous cell carcinoma of the oropharynx treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by radiotherapy and cisplatin versus radiotherapy and cisplatin only. Compare the progression-free survival in patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare the quality of life and functional status of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to primary cancer site (base of tongue vs other), nodal extent (N0-1 vs N2-3), radiotherapy plan (conventional [2-D or 3-D conformal radiotherapy] vs intensity modulated radiotherapy). Patients are randomized to 1 of 2 treatment arms. Arm I (induction chemotherapy with or without salvage surgery followed by chemoradiotherapy) Induction chemotherapy with or without early salvage surgery: Patients receive docetaxel IV over 1 hour and cisplatin over 30-60 minutes on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 21 days for 1-3 courses. Patients achieving complete or partial response at the primary site after course 1 receive 2 additional courses of therapy and then proceed to chemoradiotherapy within 3-4 weeks after completion of fluorouracil administration. Patients with stable disease or surgically resectable locoregional disease progression undergo early salvage surgery and then proceed to concurrent chemoradiotherapy within 70 days after surgery. Patients with locoregional unresectable disease progression or patients who refused early salvage surgery proceed directly to concurrent chemoradiotherapy within 3-4 weeks after completion of fluorouracil administration. Chemoradiotherapy: Patients undergo 2-D or 3-D conformal radiotherapy or intensity modulated radiotherapy once daily 5 days a week for 7 weeks and receive cisplatin IV over 30-60 minutes concurrently on days 1, 22, and 43* in the absence of disease progression or unacceptable toxicity. NOTE: *Patients undergoing surgery before chemoradiotherapy receive cisplatin on days 1 and 22 only of a 6-week course of radiotherapy. Arm II (chemoradiotherapy only): Patients undergo 2-D or 3-D conformal radiotherapy or intensity modulated radiotherapy once daily 5 days a week for 7 weeks and receive cisplatin IV over 30-60 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, after completion of chemoradiotherapy, and then at 12 months after randomization. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: Approximately 398 patients (199 per treatment arm) will be accrued for this study.

Official Title
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A Phase III Trial of Standard Fractionation Radiation and Concurrent Single Agent Cisplatin, With and Without Docetaxel, Cisplatin, and 5-Fluorouracil Induction Chemotherapy, in Patients With Advanced Oropharyngeal Squamous Cell Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: docetaxel
* Drug: 5-fluorouracil
* Procedure: surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the oropharynx by biopsy or fine needle aspiration of the primary lesion or neck mass Selected stage III or IV disease No T1-2, N1 disease No T4b disease No other primary tumor sites or unknown primary tumor sites Previously untreated disease Measurable or non-measurable disease by clinical exam, CT scan or MRI Disease considered to be curatively resectable Patients for whom surgical excision is unlikely to result in clear margins are not eligible, including patients with any of the following: Gross extension of tumor to skull base (e.g., T4b disease) Severe trismus Pterygoid plate erosion Sphenoid bone or foramen ovale involvement Direct extension to involve prevertebral-fascia Extension to superior nasopharynx or eustachian tube Direct extension into the neck with involvement of the deep neck musculature (neck node fixation) Suspected invasion (encasement) of the common or internal carotid arteries (T4b) Direct extension of neck disease to involve the external skin Regional metastases to the supraclavicular neck (IVB low level VB nodes) Disease must be appropriate for definitive radiotherapy with curative intent No evidence of distant metastases (M1) Must have negative chest x-ray PATIENT CHARACTERISTICS: Zubrod performance status 0-1 No myocardial infarction within the past 3 months No unstable or uncontrolled angina No active systemic infection Granulocyte count > 1,500/mm^3 Platelet count > 100,000/mm^3 Creatinine < 1.5 mg/dL Bilirubin normal Alkaline phosphatase ≤ 2 times upper limit of normal (ULN) SGOT or SGPT ≤ 1.5 times ULN Not pregnant or nursing Fertile patients must use effective contraception No history of hypersensitivity reaction to products containing polysorbate 80 No medical contraindication to surgery as defined by the treating institution No clinically significant motor or sensory neuropathy ≥ grade 2 No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I or II cancer from which the patient is in complete remission PRIOR CONCURRENT THERAPY: No prior therapeutic surgery for head and neck cancer No prior radiotherapy No prior chemotherapy

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 |
| --- | --- |
| Active Comparator: cisplatin/RT alone<br>cisplatin and radiation therapy | Drug: cisplatin<br> <br> * Other names: platinol;Radiation: radiation therapy<br> <br> |
| Experimental: induction chemo followed by cisplatin/RT<br>docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by surgery and/or cisplatin and radiation therapy | Drug: cisplatin<br> <br> * Other names: platinol;Drug: docetaxel<br> <br> * Other names: taxotere;Drug: 5-fluorouracil<br> <br> * Other names: 5-FU;Procedure: surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 2 years |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival by FACT-HN CTCAE v 3.0 at 2 years |  | 2 years | 
| Toxicity by CTCAE v 3.0 after induction chemotherapy or after chemotherapy and radiotherapy |  | after chemotherapy | 
| Incidence of surgical resection |  | after treatment | 
| Site of relapse |  | at relapse | 
| Quality of life by FACT-HN week 19 after first and second registration date (arm 1) |  | after first and second registrations | 

 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