Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer - Full Text View

Sponsor:	Radiation Therapy Oncology Group
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group Cancer and Leukemia Group B Southwest Oncology Group North Central Cancer Treatment Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003596

Purpose

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.

Condition	Intervention	Phase
Anal Cancer	Drug: cisplatin Drug: fluorouracil Drug: mitomycin C Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Anal Cancer Cancer

Drug Information available for: Mitomycin Fluorouracil Cisplatin Mitomycins

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	650
Study Start Date:	October 1998
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Detailed Description:

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003596

Show 485 Study Locations

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Cancer and Leukemia Group B

Southwest Oncology Group

North Central Cancer Treatment Group

Investigators

Study Chair:	Jaffer A. Ajani, MD	M.D. Anderson Cancer Center
Study Chair:	Al B. Benson, MD, FACP	Robert H. Lurie Cancer Center
Study Chair:	Joel E. Tepper, MD	UNC Lineberger Comprehensive Cancer Center
Study Chair:	John S. MacDonald, MD	Beth Israel Comprehensive Cancer Center - West Side Campus
Study Chair:	Michael G. Haddock, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett CG. Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: the intergroup trial (RTOG 98-11). Cancer. 2010 Jun 8; [Epub ahead of print]

Gunderson LL, Moughan J, Ajani JA, et al.: Anal carcinoma: Impact of TN category of disease on survival, disease relapse, and colostomy failure in U.S. GI Intergroup RTOG 98-11 phase III trial. [Abstract] American Society of Clinical Oncology 2010 Gastrointestinal Cancers Symposium, 22-24 January 2010, Orlando, Florida. A-285, 2010.

Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett CG. US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy. J Clin Oncol. 2009 Jan 12; [Epub ahead of print]

Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett C. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008 Apr 23;299(16):1914-21.

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.

Ben-Josef E, Moughan J, Ajani JA, Flam M, Gunderson L, Pollock J, Myerson R, Anne R, Rosenthal SA, Willett C. Impact of Overall Treatment Time on Survival and Local Control in Patients With Anal Cancer: A Pooled Data Analysis of Radiation Therapy Oncology Group Trials 87-04 and 98-11. J Clin Oncol. 2010 Oct 18; [Epub ahead of print]

Glynne-Jones R, Mawdsley S. Anal cancer: is neoadjuvant cisplatin chemotherapy or chemoradiotherapy friend or foe? Nat Clin Pract Oncol. 2008 Oct 14; [Epub ahead of print]

ClinicalTrials.gov Identifier:	NCT00003596 History of Changes
Other Study ID Numbers:	CDR0000066667, RTOG-9811, CALGB-89808, ECOG-R9811, NCCTG-R9811, SWOG-R9811, GUMC-00125
Study First Received:	November 1, 1999
Last Updated:	December 13, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage II anal cancer
stage III anal cancer
squamous cell carcinoma of the anus
cloacogenic carcinoma of the anus
basaloid carcinoma of the anus

Additional relevant MeSH terms:

Anus Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Mitomycins
Mitomycin

Cisplatin
Fluorouracil
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 09, 2012