Combination Chemotherapy and Intensity-Modulated Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer

A Phase II Evaluation of Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy (IMRT) in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects and how well giving combination chemotherapy together with intensity-modulated radiation therapy works in treating patients undergoing surgery for locally advanced rectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: oxaliplatin; Drug: capecitabine; Procedure: resection; Radiation: radiation therapy; Drug: FOLFOX

Detailed Description

OBJECTIVES:

Primary

• To determine whether the incidence of neoadjuvant acute gastrointestinal toxicity (grade ≥ 2) associated with neoadjuvant chemoradiotherapy is reduced by inverse-planned intensity-modulated radiotherapy (IMRT)-based radiation treatment when compared with conventionally delivered radiotherapy, as was utilized in the capecitabine and oxaliplatin arm of RTOG-0247 (NCT00081289).

Secondary

• To evaluate the feasibility of performing IMRT in a cooperative group setting for the treatment of rectal cancer.
• To estimate the incidence of all toxicity (hematologic and non-hematologic) associated with protocol treatment in the neoadjuvant period, the adjuvant period, and overall.
• To estimate the pathologic complete response rate following neoadjuvant IMRT-based chemoradiotherapy.
• To estimate the time to treatment failure and patterns of failure.
• To correlate pre- and post-treatment levels of serum cytokines with symptoms during and pathological outcomes following neoadjuvant chemoradiotherapy for rectal cancer.
• To evaluate the rate of abdominoperineal resections.

OUTLINE: This is a multicenter study.

• Chemoradiotherapy: Patients undergo inverse-planned intensity-modulated radiotherapy to the pelvis once daily, 5 days a week, for 5 weeks (total of 45 Gy) and a 3-dimensional conformal radiotherapy boost to gross disease once daily for 3 days (total of 45 Gy). Beginning on the first day of radiotherapy and continuing through completion of radiotherapy, patients receive oral capecitabine twice daily, 5 days a week, for 5 weeks and oxaliplatin IV over 2 hours on days 1, 8, 15, 22, 29.
• Surgery: Within 4-8 weeks after completion of chemoradiotherapy, patients undergo resection of the rectal tumor.
• Adjuvant chemotherapy: Beginning 4-8 weeks after surgery, patients with completely resected disease and negative surgical margins receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV bolus on day 1 and fluorouracil IV infusion continuously over 46 hours beginning on day 1 . Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months after the start of treatment for 2 years, every 6 months for years 3-5, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Providence Cancer Center at Providence Hospital
  • California
    • Auburn, California, United States, 95603
      • Auburn Radiation Oncology
    • Cameron Park, California, United States, 95682
      • Radiation Oncology Centers - Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy Cancer Center at Mercy San Juan Medical Center
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Fresno, California, United States, 93720
      • California Cancer Center - Woodward Park Office
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Roseville, California, United States, 95661
      • Radiation Oncology Center - Roseville
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • San Diego, California, United States, 92161
      • Veterans Affairs Medical Center - San Diego
    • Vacaville, California, United States, 95687
      • Solano Radiation Oncology Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Miami, Florida, United States, 33176
      • Baptist-South Miami Regional Cancer Program
    • Orange Park, Florida, United States, 32073
      • Integrated Community Oncology Network - Orange Park
    • Panama City, Florida, United States, 32401
      • Bay Medical
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
    • Savannah, Georgia, United States, 31403-3089
      • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Cancer Institute at St. John's Hospital
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint John's Cancer Center at Saint John's Medical Center
    • Goshen, Indiana, United States, 46526
      • Center for Cancer Care at Goshen General Hospital
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Oncology Center
    • Muncie, Indiana, United States, 47303-3499
      • Cancer Center at Ball Memorial Hospital
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's Hospital - South
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Brigham and Women's Cancer Center
    • Fall River, Massachusetts, United States, 02721
      • Hudner Oncology Center at Saint Anne's Hospital - Fall River
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology, PA - Maplewood
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Cancer Center
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • St. Francis Cancer Center at St. Francis Medical Center
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology, PA - Woodbury
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Cancer Institute of Cape Girardeau, LLC
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center - Hospital Hill
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute at Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64114
      • St. Joseph Medical Center
    • Kansas City, Missouri, United States, 64116
      • Parvin Radiation Oncology
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Hospital
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Barnes-Jewish West County Hospital
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
    • Reno, Nevada, United States, 89502
      • Renown Institute for Cancer at Renown Regional Medical Center
  • New Hampshire
    • Keene, New Hampshire, United States, 03431
      • Kingsbury Center for Cancer Care at Cheshire Medical Center
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Long Branch, New Jersey, United States, 07740-6395
      • Monmouth Medical Center
    • Marlton, New Jersey, United States, 08053
      • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
    • Toms River, New Jersey, United States, 08755
      • J. Phillip Citta Regional Cancer Center at Community Medical Center
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Cancer Center at Maimonides Medical Center
    • Lake Success, New York, United States, 11042
      • Monter Cancer Center of the North Shore-LIJ Health System
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • Don Monti Comprehensive Cancer Center at North Shore University Hospital
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
  • Ohio
    • Akron, Ohio, United States, 44309-2090
      • Summa Center for Cancer Care at Akron City Hospital
    • Barberton, Ohio, United States, 44203
      • Barberton Citizens Hospital
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
    • Salem, Ohio, United States, 44460
      • Cancer Care Center, Incorporated
    • West Chester, Ohio, United States, 45069
      • Precision Radiotherapy at University Pointe
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Oncology Services
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Rosenfeld Cancer Center at Abington Memorial Hospital
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Dale and Frances Hughes Cancer Center at Pocono Medical Center
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Media, Pennsylvania, United States, 19063
      • Riddle Memorial Hospital Cancer Center
    • Milford, Pennsylvania, United States, 18337
      • Upper Delaware Valley Cancer Center
    • Paoli, Pennsylvania, United States, 19301-1792
      • Cancer Center of Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Philadelphia, Pennsylvania, United States, 19114
      • Frankford Hospital Cancer Center - Torresdale Campus
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - Main Line Health
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Comprehensive Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
  • Tennessee
    • Kingsport, Tennessee, United States, 37662
      • Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84720
      • Sandra L. Maxwell Cancer Center
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84103
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center - North
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Norton, Virginia, United States, 24273
      • Southwest Virginia Regional Cancer Center at Wellmonth Health
  • Wisconsin
    • Mequon, Wisconsin, United States, 53097
      • Columbia Saint Mary's Hospital - Ozaukee
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia-Saint Mary's Cancer Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Pathologically confirmed diagnosis of adenocarcinoma of the rectum by biopsy technique that does not completely excise the lesion (e.g., fine needle aspiration, core needle biopsy)

  • Located up to 12 cm from the anal verge with no extension of malignant disease into the anal canal

  • Clinically determined to be stage T3 or T4,N0-N2, and M0 tumor as determined by the following assessments:

    • Colonoscopy and biopsy within 56 days prior to registration
    • History/physical examination (including medication history screen for contraindications) within 56 days prior to registration
    • Contrast-enhanced imaging of the abdomen and pelvis either by computed tomography(CT), MRI, or Positron-emission tomography(PET)-CT (whole body preferred) within 56 days prior to registration
    • Chest x-ray (or CT) of the chest within within 56 days prior to registration to exclude distant metastases (except for patients who have had whole body PET-CT)

    • Transrectal ultrasound (TRUS) within 56 days prior to registration required to establish tumor stage

      • TRUS not required if clinical exam, CT of the pelvis, and/or MRI demonstrates T4 lesion
• No synchronous primary colon carcinoma
• No evidence of distant metastases (M1)

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Zubrod performance status 0-2
• Absolute neutrophil count (ANC) ≥ 1,800/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dL allowed)
• Aspartate aminotransferase (AST) < 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase < 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• Creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior invasive malignancy except nonmelanoma skin cancer unless disease free for a minimum of 3 years

Exclusion criteria:

• Severe, active comorbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the past 12 months
  • Transmural myocardial infarction within the past 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • AIDS
  • Evidence of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake
  • Known, existing uncontrolled coagulopathy, unless clinically stable on anticoagulation therapy for ≥ 2 weeks
  • Evidence of peripheral neuropathy ≥ grade 2
• Prior allergic reaction to oxaliplatin or capecitabine
• Lack of physical integrity of the gastrointestinal tract (i.e., severe Crohn disease that results in malabsorption; significant bowel resection that would make one concerned about the absorption of capecitabine) or malabsorption syndrome that would preclude feasibility of oral chemotherapy (i.e., capecitabine)
• Prior systemic chemotherapy for colorectal cancer (prior chemotherapy allowed provided it was for a cancer other than colorectal cancer)
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
• Major surgery within 28 days of study enrollment(other than diverting colostomy without tumor resection)
• Participation in any investigational drug study within 28 days of study enrollment.
• Concurrent cimetidine, amifostine, and/or depot Sandostatin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: IMRT + Chemotherapy , Resection, Postoperative Chemotherapy; Radiation therapy (intensity modulated radiation therapy [IMRT] + three dimensional conformal radiation therapy [3D-CRT]) + neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by resection and postoperative chemotherapy (FOLFOX)

Drug: oxaliplatin; Other Names: 50 mg/m^2 IV over 2 hours weekly for five weeks starting on day 1 of radiotherapy.; Drug: capecitabine; 1650 mg/m^2/day orally 5 days/week during radiotherapy.; Procedure: resection; All patients undergo surgery 4 to 8 weeks following the completion of radiation therapy. The choice of procedure (abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis) is at the discretion of the surgeon.; Radiation: radiation therapy; Pelvic intensity modulated radiation therapy (IMRT): 45 Gy in 25 fx Three dimensional conformal radiation therapy (3D-CRT) boost: 5.4 Gy in 3 fx to total dose of 50.4 Gy in 28 fx; Drug: FOLFOX; Postoperative chemotherapy is administered to all patients who have a complete resection of rectal cancer with negative surgical margins and begins within 4-8 weeks following surgical resection, consisting of a total of 9 14-day cycles. Oxaliplatin 85 mg/m^2, IV over 2 hours, day 1. Leucovorin 400 mg/m^2, IV over 2 hours, day 1. 5-fluorouracil bolus 400 mg/m^2, IV push, day 1. 5-fluorouracil infusion 2400 mg/m^2, IV continuous infusion over 46 hours, day 1.; Other Names: Oxaliplatin, leucovorin, 5-fluorouracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients Experiencing Treatment-related Gastrointestinal Adverse Events ≥ Grade 2 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0, Occurring Preoperatively	The percentage of patients experiencing preoperative treatment-related gastrointestinal adverse events ≥ grade 2. If patient did not receive surgery, then such adverse events <= 90 days from the start of concurrent treatment are included.	From start of treatment to surgery or ≤ 90 days from the Start of Concurrent Treatment (for patients not undergoing surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients in Protocol Adherence Categories for Intensity-modulated Radiotherapy (IMRT) Planning	Real-time quality assurance was performed remotely by the study chair or the radiation oncology co-chair prior to initiation of treatment for the first 40 cases. The final cases enrolled were reviewed within 3 months after accrual was completed. Review included evaluation of clinical target volume (CTV) and planning target volume (PTV), Organs at Risk (OARs), and treatment plan dosimetry.	Pretreatment
Number of Patients With Pathologic Complete Response	Pathologic complete response is defined as no evidence of residual cancer histologically in the resection specimen.	At the time of surgery, which is 4-8 weeks after radiation therapy, approximately 9-13 weeks from treatment start.
Percentage of Patients With Grade 3 or Higher Treatment-related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v3.0	Grade refers to the severity of the adverse event (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. Adverse events were compiled in four different time periods: 1) Preoperative: Preoperatively or, if no surgery, then ≤ 90 days from the Start of Concurrent Treatment; 2) Postoperative#1: Postoperatively and ≤ 30 days from the Date of Surgery; 3) Postoperative#2: Postoperatively and ≤ 90 days from the End of Postoperative Chemotherapy; 4) Overall: From start of concurrent treatment to end of follow-up;	From study registration to end of follow-up. Maximum follow-up at time of analysis was 5.2 years.
Local-regional Failure: 4-year Rate	Local failure is defined as: (1) any recurrence or surgery to the primary site after a complete response (CR) reported at surgery or reported after the end of protocol treatment; or (2) persistence [failure at one day post study entry], absence of CR after protocol treatment was completed and patient lived at least 90 days from the end of treatment. Regional failure is defined as: (1) any recurrence after a nodal CR reported at surgery or reported after the end of protocol treatment; or (2) persistence, absence of nodal CR after protocol treatment was completed and patient lived at least 90 days from the end of treatment. Local-regional failure time is defined as time from registration to local or regional failure, last known follow-up (censored), or death (competing risk). Local-regional failure rates are estimated by the cumulative incidence method.	From registration to four years
Distant Failure: 4-year Rate	Distant failure is defined as the appearance of peritoneal seeding or distant metastases. Time to distant failure is defined as time from registration to the date of distant failure, last known follow-up (censored), or death (competing risk). Distant failure rates are estimated by the cumulative incidence method.	From registration to four years
Overall Survival: 4-year Rate	Overall survival time is defined as time from registration 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 four years
Disease-free Survival: 4-year Rate	Disease is defined as local-regional failure or distant failure. Distant failure is defined as the appearance of peritoneal seeding or distant metastases. Local-regional failure is defined as: (1) any recurrence or surgery to the primary site after a complete response (CR) / any recurrence after a nodal CR - reported at surgery or reported after the end of protocol treatment; or (2) persistence [failure at one day post study entry], absence of primary/nodal CR after protocol treatment was completed and patient lived at least 90 days from the end of treatment. Disease-free survival time is defined as time from registration to the date of disease, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.	From registration to four years
Number of Patients Who Underwent Abdominoperineal Resection	All patients were to undergo surgery 4 to 8 weeks following the completion of radiation therapy. The choice of procedure (abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis) was at the discretion of the surgeon. If more than 28 patients received abdominoperineal resection, this would result in a conclusion of an excessive number of abdominoperineal resections.	Surgery occurred 4 to 8 weeks following the completion of radiation therapy, approximately 9-13 weeks from start of treatment.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Principal Investigator: Michael C. Garofalo, MD, University of Maryland Greenebaum Cancer Center; Study Chair: Adam C. Berger, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University; Study Chair: Johanna Bendell, MD, Duke Cancer Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: February 9, 2008
• First Submitted That Met QC Criteria: February 9, 2008
• First Posted (Estimate): February 12, 2008

Study Record Updates

• Last Update Posted (Actual): September 25, 2018
• Last Update Submitted That Met QC Criteria: August 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Capecitabine; Oxaliplatin; Leucovorin
• Other Study ID Numbers: RTOG-0822; CDR0000586277