Radiation Therapy Plus Fluorouracil With or Without Additional Chemotherapy in Treating Patients With Primary Anal 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 use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known if fluorouracil plus radiation therapy is more effective with or without additional chemotherapy in treating anal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil plus radiation therapy with or without additional chemotherapy in treating patients who have primary anal cancer.

Detailed Description
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OBJECTIVES: Compare the response rates in patients with primary epidermoid anal cancer treated with radiotherapy and fluorouracil with either mitomycin or cisplatin and with or without maintenance therapy. Compare local control and prevention or delay of disease dissemination in patients treated with these regimens. OUTLINE: This is randomized, open-label, multicenter study. Patients are randomized to one of four treatment arms. All patients undergo radiotherapy daily 5 days a week for 5.5 weeks. All patients also receive fluorouracil IV continuously over days 1-4 and 29-32. Arm I: Patients receive mitomycin IV on day 1. Arm II: Patients receive cisplatin IV on days 1 and 29. Arm III: Patients receive mitomycin as in arm I and maintenance therapy comprising fluorouracil IV continuously over days 1-4 and cisplatin IV on day 1 beginning 4-8 weeks after completion of primary therapy and repeating once 3 weeks later. Arm IV: Patients receive cisplatin as in arm II and maintenance therapy as in arm III. Patients are followed at 2 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 600 patients (150 per treatment arm) will be accrued for this study.

Official Title
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Second UK Phase III Anal Cancer Trial: A Trial of Chemoradiation and Maintenance Therapy for Patients With Anal Cancer

Conditions
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Anal Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary epidermoid anal cancer Squamous cell Basaloid Cloacogenic No adenocarcinoma, malignant melanoma, mucoepidermoid carcinoma, lymphoma, or microinvasive anal intraepithelial neoplasia (without evidence of invasive disease) in the anal canal or margin No metastatic disease PATIENT CHARACTERISTICS: Age: Not specified Performance status: 0-2 Life expectancy: Not specified Hematopoietic: WBC greater than 3,000/mm^3 Platelet count greater than 100,000/mm^3 Hemoglobin greater than 10 g/dL Hepatic: Liver function tests no greater than 2 times normal Renal: Glomerular filtration rate at least 50 mL/min Cardiovascular: No cardiovascular disease No uncontrolled angina pectoris No heart failure No clinically significant cardiac arrhythmias Other: HIV negative No other significant concurrent illness Not predominately bed-bound or frail No severe sepsis No other prior or concurrent cancer or illness that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to pelvis Surgery: Not specified Other: No prior therapy for anal cancer
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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: fluorouracil|nan|
|Drug: mitomycin C|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate at 6 months |  |  | 
| Acute toxicity as measured up to 4 weeks after chemoradiation |  |  | 
| Recurrence-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colostomy rate |  |  | 
| In field recurrence rate as measured by confirmed disease within radiation therapy field |  |  | 
| Cause-specific and overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I anal cancer, stage II anal cancer, stage IIIA anal cancer, stage IIIB anal cancer, squamous cell carcinoma of the anus, cloacogenic carcinoma of the anus, basaloid carcinoma of the anus