Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	18 and over	NCI	RTOG-9811 CALGB-89808, ECOG-R9811, NCCTG-R9811, SWOG-R9811, GUMC-00125, RTOG-98-11, NCT00003596

Objectives

1. 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.
2. Identify any differences in local control and colostomy rates at 2 years in patients treated with these regimens.
3. Determine any difference in colostomy free, disease free, or overall survival in patients treated with these regimens.
4. Compare the toxic effects of these regimens in these patients.
5. Evaluate the prognostic effects of tumor markers P53 overexpression, human papilloma virus status, and enzyme HAP1 in patients treated with these regimens.

Entry 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

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm³
• Absolute neutrophil count at least 1,800/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

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.

Ajani JA, Winter KA, Gunderson LL, et al.: US intergroup anal carcinoma trial: tumor diameter predicts for colostomy. J Clin Oncol 27 (7): 1116-21, 2009.[PUBMED Abstract]

Ajani JA, Winter KA, Gunderson LL, et al.: Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299 (16): 1914-21, 2008.[PUBMED Abstract]

Ajani JA, Winter KA, Gunderson LL, et al.: Intergroup RTOG 98-11: a phase III randomized study of 5-fluorouracil (5-FU), mitomycin, and radiotherapy versus 5-fluorouracil, cisplatin and radiotherapy in carcinoma of the anal canal. [Abstract] J Clin Oncol 24 (Suppl 18): A-4009, 2006.

Gunderson LL, Winter KA, Ajani JA, et al.: Intergroup RTOG 9811 phase III comparison of chemoradiation with 5-FU and mitomycin vs 5-FU and cisplatin for anal canal carcinoma: impact on disease-free, overall and colostomy-free survival. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-43, S24, 2006.

Glynne-Jones R, Mawdsley S: Anal cancer: is neoadjuvant cisplatin chemotherapy or chemoradiotherapy friend or foe? Nat Clin Pract Oncol 5 (12): 692-3, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Jaffer Ajani, MD, Protocol chair		Ph: 713-792-2828; 800-392-1611 Email: jajani@mdanderson.org

Eastern Cooperative Oncology Group

Al Benson, MD, FACP, Protocol chair		Ph: 312-695-6180

Cancer and Leukemia Group B

Joel Tepper, MD, Protocol chair		Ph: 919-966-0400 Email: tepper@med.unc.edu

Southwest Oncology Group

John MacDonald, MD, Protocol chair		Ph: 212-604-6011; 888-442-2623

North Central Cancer Treatment Group

Michael Haddock, MD, Protocol chair		Ph: 507-284-2511

Registry Information
Official Title		A Phase III Randomized Study of 5-Fluorouracil, Mitomycin-C, and Radiotherapy Versus 5-Fluorouracil, Cisplatin, and Radiotherapy in Carcinoma of the Anal Canal
Trial Start Date		1998-10-31
Trial Completion Date		2008-04-23
Registered in ClinicalTrials.gov		NCT00003596
Date Submitted to PDQ		1998-09-25
Information Last Verified		2005-06-15
NCI Grant/Contract Number		CA21661