Radiation Therapy, Mitomycin, and Either Fluorouracil or Cisplatin in Treating Patients With Locally Advanced Anal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as mitomycin, fluorouracil, and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known whether radiation therapy and mitomycin are more effective when combined with fluorouracil or with cisplatin in treating anal cancer . PURPOSE: This randomized phase II/III trial is studying how well giving radiation therapy and mitomycin together with fluorouracil works compared to radiation therapy, mitomycin, and cisplatin in treating patients with locally advanced anal cancer.

Detailed Description
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OBJECTIVES: Phase II Primary Compare the early clinical response (tumor response at 8 weeks) of patients with locally advanced anal cancer treated with radiotherapy with mitomycin and cisplatin vs mitomycin and fluorouracil. Secondary Compare the feasibility of these regimens in these patients. Compare the acute toxicity of these regimens in these patients. Compare patient compliance to these regimens. Phase III Primary Compare the event-free survival of patients treated with these regimens. Secondary Compare colostomy-free, disease-free, and overall survival of patients treated with these regimens. Compare locoregional control in patients treated with these regimens. Compare the late toxicity of these regimens in these patients. Compare quality of life of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, T stage (T2 vs T3 vs T4), and nodal status (N0 vs N+). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo radiotherapy once daily 5 days a week on weeks 1-4, 7-8, and 3 days of week 9 (total of 33 fractions). Patients concurrently receive fluorouracil IV continuously on days 1-26 and 43-59 and mitomycin IV over 15 minutes on days 1 and 43. Arm II: Patients receive radiotherapy and mitomycin as in arm I and cisplatin IV over 1 hour on days 1, 8, 15, 22, 43, 50, and 57. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at weeks 12 and 26, and then every 6 months for 2 years. Patients are followed every 2 weeks for 8 weeks, at week 26, and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 678 patients (80 [40 per treatment arm] for phase II and 598 [299 per treatment arm] for phase III) will be accrued for this study within 2-5 years.

Official Title
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Continuous Fluorouracil Plus Mitomycin C Versus Mitomycin C Plus Cisplatin As Chemotherapy Combination In Combined Radiochemotherapy For Locally Advanced Anal Cancer. A Phase II-III Study

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 squamous cell anal carcinoma Keratinizing or non-keratinizing The following stages are eligible: T2, N0, M0 with maximum tumor diameter at least 4 cm T3-T4, N0, M0 Any T, N1-N3, M0 Tumor located in the anal canal OR in the anal margin and infiltrating the anal canal No primary adenocarcinoma of the anus Measurable disease PATIENT CHARACTERISTICS: Age 18 to 75 Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Granulocyte count greater than 2,000/mm^3 Platelet count greater than 100,000/mm^3 Hepatic Not specified Renal Creatinine less than 1.4 mg/dL Cardiovascular No grade I angina pectoris with clinical symptoms within the past 3 months No grade II-IV angina pectoris within the past 3 months No stage II or greater distal arteritis Other Not pregnant or nursing Fertile patients must use effective contraception No other prior malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No other concurrent radiotherapy Surgery No prior colostomy Other No prior treatment for anal cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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


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 |
| --- | --- | --- |
| Response as measured by RECIST at 8 weeks after completion of study treatment (Phase II) |  |  | 
| Event-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity and compliance to treatment as measured by CTC v 2.0 at completion of study treatment (Phase II) |  |  | 
| Colostomy-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III) |  |  | 
| Overall survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter |  |  | 
| Disease-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter |  |  | 
| Local control as measured by Gray at 12 and 26 weeks, then every 6 months thereafter |  |  | 
| Late toxicity as measured by RTOG and EROTC every 6 months after week 26 |  |  | 
| Quality of life as measured by EORTC Quality of Life Questionnaire-C30 and ASCT at 12 and 26 weeks, then every 6 months for 2 years after entry |  |  | 

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