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.

Condition	Treatment or Intervention	Phase
Anal Cancer basaloid carcinoma of the anus cloacogenic carcinoma of the anus squamous cell carcinoma of the anus	Drug: cisplatin  Drug: fluorouracil  Drug: mitomycin  Procedure: chemotherapy  Procedure: radiation therapy	Phase III

Further Study Details: 

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.

PROJECTED ACCRUAL: A total of 600 patients (150 per treatment arm) will be accrued for this study.

Genders Eligible for Study:  Both

Criteria

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

United Kingdom, England
      Cancer Research Centre at Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom; Recruiting
      Cancer Research UK and University College London Cancer Trials Centre, London,  England,  NW1 2ND,  United Kingdom; Recruiting
      Cookridge Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS16 6QB,  United Kingdom; Recruiting
      Ipswich Hospital NHS Trust, Ipswich,  England,  IP4 5PD,  United Kingdom; Recruiting
      Mount Vernon Hospital, Northwood,  England,  HA6 2RN,  United Kingdom; Recruiting
      Northwick Park Hospital, Harrow,  England,  HA1 3UJ,  United Kingdom; Recruiting
      Nottingham City Hospital NHS Trust, Nottingham,  England,  NG5 1PB,  United Kingdom; Recruiting
      Royal Marsden NHS Foundation Trust - Surrey, Sutton,  England,  SM2 5PT,  United Kingdom; Recruiting
      Saint Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom; Recruiting
      South Tees Hospitals NHS Trust, Middlesbrough, Cleveland,  England,  TS4 3BW,  United Kingdom; Recruiting
      Southend NHS Trust Hospital, Westcliff-On-Sea,  England,  SS0 0RY,  United Kingdom; Recruiting
United Kingdom, Scotland
      Aberdeen Royal Infirmary, Aberdeen,  Scotland,  AB25 2ZN,  United Kingdom; Recruiting
United Kingdom, Wales
      Velindre Cancer Center at Velinde Hospital, Cardiff,  Wales,  CF14 2TL,  United Kingdom; Recruiting

Study chairs or principal investigators

Roger D. James, MD,  Study Chair,  Maidstone Hospital   

Study ID Numbers:  CDR0000068911; NCRI-ACT-II; EU-20056; UKCCCR-ACT-II; NCT00025090
Record last reviewed:  March 2002
Last Updated:  April 4, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025090
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08