Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Closed	18 to 75	Other	EORTC-22011 EORTC-40014, NCT00068744

Objectives

Phase II

Primary

1. 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

1. Compare the feasibility of these regimens in these patients.
2. Compare the acute toxicity of these regimens in these patients.
3. Compare patient compliance to these regimens.

Phase III

Primary

1. Compare the event-free survival of patients treated with these regimens.

Secondary

1. Compare colostomy-free, disease-free, and overall survival of patients treated with these regimens.
2. Compare locoregional control in patients treated with these regimens.
3. Compare the late toxicity of these regimens in these patients.
4. Compare quality of life of patients treated with these regimens.

Entry Criteria

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

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

Patient Characteristics:

Age

• 18 to 75

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count greater than 2,000/mm³
• Platelet count greater than 100,000/mm³

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

Expected Enrollment

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.

Outcomes

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)

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

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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Jean-Francois Bosset, MD, Protocol chair		Ph: 33-381-668310 Email: jean-francois.bosset@ufc-chu.univ-fcomte.fr

Registry Information
Official Title		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
Trial Start Date		2003-07-29
Registered in ClinicalTrials.gov		NCT00068744
Date Submitted to PDQ		2003-08-04
Information Last Verified		2007-10-07