Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer

Anal Cancer Clinical Trial

Official title:

A Phase II Evaluation of Dose-Painted Intensity-Modulated Radiation Therapy (IMRT) in Combination With 5-Fluorouracil (5-FU) and Mitomycin-C for Reduction of Acute Morbidity in Carcinoma of the Anal Canal

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423293
• Other study ID #: RTOG-0529
• Secondary ID: CDR0000524057
• Status: Completed
• Phase: Phase 2
• Start date: December 2006
• Est. completion date: December 2016

Study information

• Verified date: February 2019
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as fluorouracil and mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with 5-fluorouracil (5-FU) and mitomycin C may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving intensity-modulated radiation therapy together with fluorouracil and mitomycin C works in treating patients with invasive anal cancer.

Description:

OBJECTIVES:

Primary

• Determine if dose-painted, intensity-modulated radiation therapy (IMRT), fluorouracil, and mitomycin C decreases the combined rate of gastrointestinal and genitourinary adverse events (grade II or greater) by at least 15% in the first 90 days after the start of treatment in patients with primary invasive carcinoma of the anal canal compared to patients treated on the radiotherapy, fluorouracil, and mitomycin C arm on clinical trial RTOG 98-11.

Secondary

• Determine the feasibility of performing IMRT in these patients in a cooperative group setting.

• Evaluate adverse events experienced by patients treated with this regimen and to decrease the grade 2 and higher and grade 3 and higher overall adverse event rates by 15% or 20% as compared to the radiotherapy and mitomycin C arm of RTOG 98-11.

• Evaluate the total duration of radiotherapy.

• Evaluate the efficacy of this regimen, in terms of locoregional failure, disease-free survival, time to colostomy, colostomy-free survival, and overall survival of these patients.

• Determine clinical complete response at 8 weeks after completion of study treatment.

OUTLINE: This is a multicenter study.

Patients receive mitomycin C IV over 10-30 minutes on days 1 and 29 and fluorouracil IV continuously over 96 hours on days 1-4 and 29-32. Patients also undergo dose-painted intensity-modulated radiation therapy once daily, 5 days a week, for 5½ to 6 weeks beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 59 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: December 2016
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma of the anal canal, including any of the following subtypes:

• Squamous cell

• Basaloid

• Cloacogenic

• Primary invasive disease

• T2-4, N0-3 disease

• Clinically positive small inguinal nodes (i.e., < 1 cm in size) must be confirmed by biopsy (preferably fine-needle aspiration) within the past 6 weeks

• Biopsy is not required for enlarged inguinal, perirectal, or pelvic nodes on exam or CT scan that are found to be = 1.0 cm and are considered to be clinically positive

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• Hemoglobin = 8.0 g/dL (transfusion or other intervention allowed)

• ALT and AST < 3 times upper limit of normal

• Absolute neutrophil count = 1,800/mm³

• Serum creatinine = 1.5 mg/dL

• Platelet count = 100,000/mm³

• Bilirubin < 1.4 mg/dL

• WBC = 3,000/mm³

• INR = 1.5

• No known AIDS

• HIV-positive patients without AIDS are eligible

• HIV test required for patients with clinical suspicion of AIDS

• No other invasive malignancy within the past 3 years except for nonmelanomatous skin cancer

• No severe, active comorbidity, defined as any of the following:

• Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months

• Transmural myocardial infarction within the past 6 months

• Acute bacterial or fungal infection requiring IV antibiotics

• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study treatment

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

• Uncontrolled diabetes mellitus, uncompensated heart disease, and/or uncontrolled high blood pressure, that in the opinion of the patient's treating physician, requires an immediate change in management

• Patients may be eligible if appropriate changes in management have resulted in adequate control of the above mentioned conditions

• Other immunocompromised status (e.g., organ transplantation or chronic glucocorticoid use)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior radiation therapy to the pelvis that would result in overlap of radiation therapy fields

• No prior systemic chemotherapy for cancer of the anus

• No prior surgery for cancer of the anus that removed all macroscopic anal cancer

• No concurrent sargramostim (GM-CSF)

• No concurrent amifostine

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms

Intervention

Drug:
• fluorouracil
1000 mg/m^2/day 96-hour continous infusion (M-F) starting on day 1 and again on day 29 of radiation therapy.
• mitomycin C
10 mg/m^2 intravenous therapy on day 1 and day 29 of radiation therapy.

Radiation:
• Intensity-modulated radiation therapy
Prescription dose depends on tumor staging. T2N0: The primary tumor PTV (planning target volume) (PTVA) receives 50.4 Gy in 28 fractions (fx) at 1.8 Gy/fx. The nodal PTVs receive 42 Gy in 28 fx at 1.5 Gy/fx. PTVA receive 50.4 Gy in 28 fractions at 1.8 Gy/fx. PTV42 receive 42 Gy in 28 fx at 1.5 Gy/fx and will include all nodal regions. T3N0 or T4N0: The primary tumor PTV (PTVA) will receive 54 Gy in 30 fx at 1.8 Gy/fx. The nodal PTVs will receive 45 Gy in 30 fx at 1.5 Gy/fx. PTVA will receive 54 Gy in 30 fx at 1.80 Gy/fx. PTV45 will receive 45 Gy in 30 fx electively at 1.5 Gy/fx and will include all nodal regions. For N+ disease: The primary tumor PTV (PTVA) will receive 54 Gy in 30 fx at 1.8 Gy/fx. For involved nodes = 3 cm in maximum dimension, the involved nodal PTV will receive 50.4 Gy in 30 fx at 1.68 Gy/fx. For involved nodes > 3 cm in maximum dimension, the involved nodal PTV will receive 54 Gy in 30 fx at 1.80 Gy/fx.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	New Mexico Cancer Center	Albuquerque	New Mexico
United States	American Fork Hospital	American Fork	Utah
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Piedmont Hospital	Atlanta	Georgia
United States	Auburn Radiation Oncology	Auburn	California
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital	Boca Raton	Florida
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Harrison Medical Center	Bremerton	Washington
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Graham Hospital	Canton	Illinois
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Memorial Hospital	Carthage	Illinois
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Texas Oncology, PA at Texas Cancer Center Dallas Southwest	Dallas	Texas
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Willamette Valley Cancer Center - Eugene	Eugene	Oregon
United States	Eureka Community Hospital	Eureka	Illinois
United States	St. Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital	Fort Worth	Texas
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Mason District Hospital	Havana	Illinois
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Central Indiana Cancer Centers - East	Indianapolis	Indiana
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	St. Vincent Oncology Center	Indianapolis	Indiana
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network at Southside Cancer Center	Jacksonville	Florida
United States	Integrated Community Oncology Network	Jacksonville Beach	Florida
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas City Cancer Centers - South	Kansas City	Missouri
United States	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Kewanee Hospital	Kewanee	Illinois
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	McDonough District Hospital	Macomb	Illinois
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Florida Oncology Associates	Orange Park	Florida
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Kansas City Cancer Centers - Southwest	Overland Park	Kansas
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Bay Medical	Panama City	Florida
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Frankford Hospital Cancer Center - Torresdale Campus	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Norris Cotton Cancer Center - North	Saint Johnsbury	Vermont
United States	Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters	Saint Peters	Missouri
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Texas Oncology, PA at Texas Cancer Center - Sherman	Sherman	Texas
United States	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Valley Cancer Center	Spring Valley	Illinois
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Arizona Oncology - Tucson	Tucson	Arizona
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	St. John Macomb Hospital	Warren	Michigan
United States	Precision Radiotherapy at University Pointe	West Chester	Ohio
United States	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia
United States	Wilmed Radiation Oncology Services	Wilson	North Carolina
United States	Cancer Treatment Center	Wooster	Ohio
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Acute Gastrointestinal (GI) and Genitourinary (GU) Adverse Events (AE) = Grade 2 as Defined by CTCAE v3.0 (Common Terminology Criteria for Adverse Events)	Highest grade adverse event per subject were counted. Adverse events were graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Acute toxicities occur within 90 days of the start of treatment.	From the start of treatment to 90 days
Secondary	Number of Patients With Major Radiation Planning Deviations	Deviations in intensity-modulated radiation therapy technique (IMRT) planning were determined by central review by the radiation oncology co-chairs of the study.	Planning occurred prior to radiation therapy
Secondary	Percentage of Subjects With Acute Adverse Events (AE)	Highest grade adverse event per subject were counted. Adverse events were graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Acute toxicities occur within 90 days of the start of treatment.	From the start of treatment to 90 days
Secondary	Percentage of Subjects With Late Adverse Events (AE)	Highest grade adverse event per subject were counted. Adverse events were graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Late toxicities occur greater than 90 days from the start of treatment.	From 91 days after start of study treatment to the end of follow-up. Maximum follow-up at time of analysis was 9.2 years.
Secondary	Clinical Complete Response Rate	A complete clinical response was defined as complete resolution of all palpable tumor determined by digital rectal exam and proctosigmoidoscopy supplemented with pelvic axial imaging.	8 and 12 weeks after treatment completion (corresponding to 14 and 18 weeks from registration)
Secondary	Duration of Radiotherapy Treatment	Number of days from radiotherapy treatment start to radiotherapy treatment end	From start to end of radiation therapy (6 weeks)
Secondary	Five-year Rate of Overall Survival	Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.	From registration to 5 years
Secondary	Five-year Rate of Disease-free Survival	Disease-free survival time is defined as time from registration to the date of local-regional failure, the appearance of distant metastases, the appearance of a second primary failure, or date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact. Local failure is defined as any measurable disease after 12 weeks from the completion of chemoradiation therapy. Local failure is defined as: a) For patients with no disease in pelvic and/or groin nodes, the appearance of disease in pelvic or groin nodes; b) For patients with disease in pelvic and/or groin nodes at study entry, nodal recurrence following clearance or persistent nodal disease for more than 12 weeks after completion of treatment.	From registration to 5 years
Secondary	Five-Year Cumulative Incidence Rate of Local-regional Failure	Local-regional failure time is defined as time from registration to date of failure and is estimated by the cumulative incidence method. Patients last known to be alive without failure are censored at the date of last contact. Local-regional failure is defined as a local or regional failure. Local failure is defined as any measurable disease after 12 weeks from the completion of chemoradiation therapy. Regional failure is defined as: a) For patients with no disease in pelvic and/or groin nodes, the appearance of disease in pelvic or groin nodes; b) For patients with disease in pelvic and/or groin nodes at study entry, nodal recurrence following clearance or persistent nodal disease for more than 12 weeks after completion of treatment.	From registration to 5 years
Secondary	Five-Year Cumulative Incidence Rate of Distant Failure	Distant failure time is defined as time from registration to the appearance of distant metastases and is estimated by the cumulative incidence method. Patients last known to be alive without failure are censored at the date of last contact.	From registration to 5 years
Secondary	Five-Year Cumulative Incidence Rate of Colostomy Failure	Colostomy failure time is defined as time from registration to the date of colostomy or abdominoperineal (A-P) resection and is estimated by the cumulative incidence method. Patients last known to be alive without failure are censored at the date of last contact.	From registration to 5 years
Secondary	Five-Year Rate of Colostomy-free Survival	Colostomy-free survival time is defined as time from registration to date of colostomy or abdominoperineal (A-P) resection, or date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact.	From registration to 5 years