Radiation Therapy Cisplatin With or Without Fluorouracil Patients With Stage III or Stage IV Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as 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. Giving radiation therapy together with cisplatin and fluorouracil may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without fluorouracil in treating patients with head and neck cancer. PURPOSE: This randomized phase III trial is studying radiation therapy and cisplatin to compare how well they work with or without fluorouracil in treating patients with stage III or stage IV head and neck cancer.

Detailed Description
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OBJECTIVES: To compare the relapse-free survival of patients treated with radiotherapy and cisplatin with vs without fluorouracil. To compare the overall survival, local control without surgery, and patterns of failure in patients treated with these regimens. To compare the acute and long-term toxicity of these regimens in these patients. To compare the quality of life of patients treated with these regimens. To prospectively collect biopsy material, mucosal scrapings, and serum in an effort to generate hypotheses for future correlative studies. OUTLINE: This is a multicenter study. Patients are stratified according to radiotherapy schedule (once daily vs twice daily) and radiotherapy planning (2D vs 3D vs intensity-modulated radiotherapy). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks and receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy. Arm II: Patients undergo radiotherapy as in arm I and receive fluorouracil IV and cisplatin IV continuously on days 1-4 and 22-25 of radiotherapy. Patients with biopsy-verified residual disease at the primary site or local recurrence after achieving a complete response to chemoradiotherapy may undergo salvage surgery 12 weeks after the completion of chemoradiotherapy. Patients complete questionnaires periodically to assess late toxicity and quality of life. After completion of study treatment, patients are followed periodically.

Official Title
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A Phase III Randomized Trial Comparing Single Agent Cisplatin With the Combination of 5-Fluorouracil and Cisplatin, Concurrent With Radiation Therapy in Stage III and IV Squamous Cell Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: fluorouracil
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx No histologic diagnosis other than squamous cell carcinoma A primary site must be identified Must have locoregionally confined stage III (excluding T1-2, N1) or stage IV disease No evidence of nodal disease below the clavicles or distant hematogenous metastases (M0) No stage IVC disease (stage IVB disease allowed) Deemed appropriate for definitive non-operative management with curative intent Resectable disease is not required No primary cancer of the nasopharynx, paranasal sinus, or salivary gland PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC > 3,500/mm³ Platelet count > 100,000/mm³ Serum creatinine < 2.0 mg/dL Alkaline phosphatase < 2 times normal AST < 2 times normal Bilirubin ≤ 2.0 mg/dL Serum calcium normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No unstable or uncontrolled angina No clinically apparent jaundice No active infection No history of any other malignancy (except squamous cell or basal cell skin cancer or cervical carcinoma in situ), unless the patient has been continuously disease-free for at least 5 years Not a poor compliance risk Able to withstand the rigors of intensive treatment Available for and compliant with adequate long-term follow-up PRIOR CONCURRENT THERAPY: No prior definitive surgery or radiotherapy for this malignancy No prior chemotherapy, immunotherapy, or epidermal growth factor receptor inhibitors for any disease Patients who have had previous definitive surgery, or radiation therapy for this malignancy, and patients who have had any previous chemotherapy, immunotherapy, or EGF receptor inhibition for any disease are ineligible. Exclusion Criteria Patients with primary cancers of the nasopharynx, paranasal sinus or salivary gland are ineligible. Patients with unstable or uncontrolled angina, clinically apparent jaundice, or active infection are ineligible. Patients with a history of any other malignancy (except squamous or basal cell skin cancer or cervical carcinoma in-situ) are ineligible, unless the patient has been continuously disease-free for at least 5 years. Patients with any histologic diagnosis other than squamous cell carcinoma are ineligible. Patients who might be a poor-compliance risk are ineligible. Pregnant or breastfeeding women are ineligible. Women/men of reproductive potential must be willing to practice acceptable methods of birth control to prevent pregnancy.

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: Arm A: Radiation with concurrent Cisplatin<br>Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks and receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy. | Drug: cisplatin<br>* Given IV<br>* Other names: CDDP;Radiation: radiation therapy<br>* Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks<br>* Other names: radiation;|
| Experimental: Arm B: Radiation with concurrent 5-FU and Cisplatin<br>Patients undergo radiotherapy as in arm I and receive fluorouracil IV and cisplatin IV continuously on days 1-4 and 22-25 of radiotherapy. | Drug: cisplatin<br>* Given IV<br>* Other names: CDDP;Drug: fluorouracil<br>* Given IV<br>Radiation: radiation therapy<br>* Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks<br>* Other names: radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Free Survival | Number of patients that are alive without recurrence when recurrence is defined by any subject with new evidence of cancer after achieving a complete response. Complete response is defined by the complete disappearance of all clinically and radiologically detectable tumor.. | at 2 yrs from start of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patterns of Failure | Patients with any new evidence of cancer after achieving a complete response are considered to have recurrent disease. Biopsy verification will be obtained if at all possible and salvage surgery is recommended if possible. Disease recurrence will be characterized as either local, regional(nodal) or distant recurrence. Patients may have more than one kind of recurrence. | 2 years from start of study | 
| Overall Survival | Number of patients still alive from 2 years from start of study | 2 yrs from start of study | 
| Number of Patients With a Clinical Response-complete Disappearance of Detectable Tumor | Twelve weeks after completing chemoradiotherapy, a formal evaluation for response will be made, to include a careful evaluation by the head and neck surgeon, medical and radiation oncologists, and, as appropriate, a radiologic and an endoscopic examination. Patients will be considered to have achieved either a clinical complete response (i.e. complete disappearance of all clinically and radiologically detectable tumor) or to have clinical persistent disease. | at 12 weeks after completing chemoradiotherapy | 
| Number of Patients With a Pathological(Final)Complete Response | A Pathological, or final response will be assigned to subjects after any salvage surgery is performed for clinical persistent disease, and after planned neck dissection in those achieving a clinical complete response. If no surgery is performed after chemoradiotherapy, the clinical and pathological (final) response will be the same. Patient will be coded as having either a pathologic complete response, or as having pathologic persistent disease. A pathologic complete response will be defined as the total disappearance of all clinically and radiologically detectable tumor. | at 12 weeks after completing chemoradiotherapy and surgery | 
| Disease Recurrence | Number of patients with any new evidence of cancer after achieving a complete response (at 12 weeks after completing chemoradiotherapy) are considered to have recurrent disease. | 2 years after start of study | 
| Number of Patients That Required a Feeding Tube |  | 12 weeks (after treatment) | 
| Number of Patients That Required a Feeding Tube |  | 8 months after start of treatment | 
| Number of Patients That Required a Feeding Tube |  | 12 months after start of treatment | 
| Number of Patients That Required a Feeding Tube |  | 24 months after start of treatment | 
| Nausea Level | Quality of life questionnaire asking I have nausea. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). N (number of patients analyzed) is based on number of patients who completed the question. | 12 weeks (after treatment) | 
| Nausea Level | Quality of life questionnaire asking I have nausea. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 8 months from start of treatment | 
| Nausea Level | Quality of life questionnaire asking I have nausea. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 months from start of treatment | 
| Nausea Level | Quality of life questionnaire asking I have nausea. | 24 months from start of treatment | 
| Dry Mouth | Quality of life questionnaire asking My mouth is dry. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 weeks (after treatment) | 
| Dry Mouth | Quality of life questionnaire asking My mouth is dry. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 8 months from start of treatment | 
| Dry Mouth | Quality of life questionnaire asking My mouth is dry. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 months from start of treatment | 
| Dry Mouth | Quality of life questionnaire asking My mouth is dry. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 24 months from start of treatment | 
| Pain | Quality of life questionnaire asking I have pain in my mouth, throat or neck. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 weeks (after treatment) | 
| Pain | Quality of life questionnaire asking I have pain in my mouth, throat or neck. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 8 months from start of treatment | 
| Pain | Quality of life questionnaire asking I have pain in my mouth, throat or neck. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 months from start of treatment | 
| Pain | Quality of life questionnaire asking I have pain in my mouth, throat or neck. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 24 months from start of treatment | 
| Quality of Life | Quality of life questionnaire asking I am content with the quality of my life right now. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 weeks (after treatment) | 
| Quality of Life | Quality of life questionnaire asking I am content with the quality of my life right now. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 8 months from start of treatment | 
| Quality of Life | Quality of life questionnaire asking I am content with the quality of my life right now. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 months from start of treatment | 
| Quality of Life | Quality of life questionnaire asking I am content with the quality of my life right now. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 24 months from start of treatment | 
| Eating | Quality of life questionnaire asking I am able to eat the foods i like. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 weeks (after treatment) | 
| Eating | Quality of life questionnaire asking I am able to eat the foods i like. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 8 months from start of treatment | 
| Eating | Quality of life questionnaire asking I am able to eat the foods i like. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 months from start of treatment | 
| Eating | Quality of life questionnaire asking I am able to eat the foods i like. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 24 months from start of treatment | 
| Swallowing | Quality of life questionnaire asking I can swallow naturally and easily. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 weeks (after treatment) | 
| Swallowing | Quality of life questionnaire asking I can swallow naturally and easily. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 8 months after start of treatment | 
| Swallowing | Quality of life questionnaire asking I can swallow naturally and easily. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 months after start of treatment | 
| Swallowing | Quality of life questionnaire asking I can swallow naturally and easily. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 24 months after start of treatment | 
| Alcohol Consumption | Quality of life questionnaire asking I drink alcohol (e.g. beer, wine). The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 weeks (after treatment) | 
| Alcohol Consumption | Quality of life questionnaire asking I drink alcohol (e.g. beer, wine). The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 8 months after start of treatment | 
| Alcohol Consumption | Quality of life questionnaire asking I drink alcohol (e.g. beer, wine). The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 months after start of treatment | 
| Alcohol Consumption | Quality of life questionnaire asking I drink alcohol (e.g. beer, wine). The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 24 months after start of treatment | 
| Solid Foods | Quality of life questionnaire asking I can eat solid foods. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 weeks (after treatment) | 
| Solid Foods | Quality of life questionnaire asking I can eat solid foods. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 8 months after start of treatment | 
| Solid Foods | Quality of life questionnaire asking I can eat solid foods. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 12 months after start of treatment | 
| Solid Foods | Quality of life questionnaire asking I can eat solid foods. The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement. | 24 months after start of treatment | 

 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 hypopharynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the larynx