Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug or combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known whether fluorouracil and mitomycin plus radiation therapy is more effective than fluorouracil and cisplatin plus radiation therapy for anal cancer.

PURPOSE: This randomized phase III trial is studying fluorouracil and mitomycin plus radiation therapy to see how well it works compared to fluorouracil and cisplatin plus radiation therapy in treating patients with stage II or stage III anal cancer.

Further Study Information

OBJECTIVES:

• Compare the initial and total local and distant failure rates in patients with anal canal cancer treated with either fluorouracil (5-FU) plus mitomycin concurrently with radiotherapy or 5-FU plus cisplatin followed by 5-FU plus cisplatin concurrently with radiotherapy.

• Identify any differences in local control and colostomy rates at 2 years in patients treated with these regimens.

• Determine any difference in colostomy free, disease free, or overall survival in patients treated with these regimens.

• Compare the toxic effects of these regimens in these patients.

• Evaluate the prognostic effects of tumor markers P53 overexpression, human papilloma virus status, and enzyme HAP1 in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to gender, nodal status (positive vs negative), and primary tumor size (greater than 2 cm to 5 cm vs greater than 5 cm). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fluorouracil (5-FU) IV continuously over 96 hours beginning on days 1 and 29 and mitomycin IV on days 1 and 29 with concurrent radiotherapy.

• Arm II: Patients receive induction chemotherapy comprising 5-FU IV continuously over 96 hours beginning on days 1, 29, 57, and 85 and cisplatin IV over 1 hour on days 1, 29, 57, and 85. Beginning on day 57, patients receive concurrent radiotherapy.

In both arms, radiotherapy is administered daily, 5 days a week, for 5-6.5 weeks. Patients with T3, T4, or N+ lesions or T2 lesions with residual disease receive additional radiotherapy to a reduced field.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 650 patients will be accrued for this study within 5 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary squamous, basaloid, or cloacogenic carcinoma of the anal canal, other than carcinoma in situ

• T2-4, Any N, M0 (stage II or III)

• No local or regional recurrence after local excision or abdominal peritoneal resection

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3

• Absolute neutrophil count at least 1,800/mm^3

• Platelet count at least 100,000/mm^3

• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin less than 1.4 mg/dL

Renal:

• Creatinine no greater than 1.5 mg/dL OR

• Creatinine clearance at least 80 mL/min

Cardiovascular:

• No uncompensated heart disease

• No uncontrolled high blood pressure

Other:

• No AIDS

• No active systemic infection

• No uncontrolled diabetes

• No other prior malignancy within the past 5 years except nonmelanoma skin cancer

• No mental condition that would preclude study participation

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior epoetin alfa allowed in lieu of blood transfusions

Chemotherapy:

• At least 5 years since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 5 years since prior radiotherapy

Surgery:

• No prior surgery of anal canal except for biopsy of study site

Trial Contact Information

Trial Lead Organizations/Sponsors

Radiation Therapy Oncology Group

Jaffer A. Ajani

Study Chair

Al Bowen Benson

Study Chair

Joel Elliott Tepper

Study Chair

John S. MacDonald

Study Chair

Michael G. Haddock

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00003596
Information obtained from ClinicalTrials.gov on November 20, 2012