Genetic Study of Young Patients With Colorectal Cancer

A Prospective Study Of The Prognostic Significance Of Microsatellite Instability In Patients With Early Age-Of-Onset Colorectal Cancer

RATIONALE: Identifying gene mutations (microsatellite instability) may allow doctors to plan effective treatment for patients who develop colorectal cancer at an early age.

PURPOSE: Genetic trial to determine the significance of gene mutations in helping predict the outcome of treatment in patients who develop stage I, stage II, or stage III colorectal cancer at an early age.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Genetic: microsatellite instability analysis

Detailed Description

OBJECTIVES:

• Evaluate the prognostic significance (e.g., overall survival) of microsatellite instability (MSI) status in patients with early age-of-onset stage I-III colorectal cancer, assuming the presence of a quantitative interaction between MSI status and family history of cancer.
• Evaluate the development of metachronous neoplasms in this patient population.
• Evaluate the histologic features and genetic changes associated with hereditary nonpolyposis colorectal cancer in this patient population.

OUTLINE: This is a multicenter study. Patients are stratified according to family history using the Amsterdam II criteria for hereditary nonpolyposis colorectal cancer (positive vs negative).

Patients undergo baseline colonoscopy before or within 6 months of initial curative resection and then surveillance colonoscopy at 1, 3, and 5 years (+/- 6 months) after resection. The number, size, location, histology, and method of removal of polyps are documented at the time of colonoscopy. Patients also undergo microsatellite instability (MSI) status testing and complete family history questionnaires at baseline.

The prognostic significance of family history and MSI status is evaluated. The individual histologic features of the tumors are compared with the MSI status to determine their predictive value. The histologic features are also correlated with outcome to determine their prognostic significance.

Patients may be referred for genetic counseling.

A certificate of confidentiality protecting the identity of research participants in this project has been issued by the National Cancer Institute.

• Study Type: Observational
• Enrollment (Actual): 651

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre
• United States
  • Alabama
    • Mobile, Alabama, United States, 36640-0460
      • Mobile Infirmary Medical Center
    • Mobile, Alabama, United States, 36608
      • Providence Cancer Center
  • California
    • Colton, California, United States, 92324-1819
      • Arrowhead Regional Medical Center
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Hospital
    • Fort Lauderdale, Florida, United States, 33308
      • Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Gainesville, Florida, United States, 32610-100277
      • Shands Cancer Center at the University of Florida Health Science Center
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Surgical Oncology of Northeast Georgia
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Community Hospital
    • Aurora, Illinois, United States, 60504-4206
      • Rush Copley Medical Center
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center at University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40503-9985
      • Central Baptist Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
    • Shreveport, Louisiana, United States, 71130-3932
      • Louisiana State University Health Sciences Center - Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Medical Center - Burlington
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Cancer Center - University Campus
  • Michigan
    • Flint, Michigan, United States, 48532
      • Great Lakes Cancer Institute - McLaren
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Digestive Health Specialists, P.A.
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68114-4199
      • Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
    • Omaha, Nebraska, United States, 68131-2197
      • Cancer Center at Creighton University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28204
      • Presbyterian Hospital
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Akron, Ohio, United States, 44302
      • Akron General's McDowell Cancer Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Oncology Services
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • Abramson Cancer Center of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15212-4772
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Cancer Center at Magee-Womens Hospital
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404-3285
      • Sarah Cannon Cancer Center at Parkridge Medical Center
    • Memphis, Tennessee, United States, 38120
      • Baptist Cancer Institute at Baptist Memorial Hospital - Memphis
    • Nashville, Tennessee, United States, 37236
      • Baptist Hospital
    • Nashville, Tennessee, United States, 37232-6860
      • Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75231
      • Presbyterian Hospital of Dallas
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Methodist Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Huntsman Cancer Institute
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - Medical Center Campus
  • Virginia
    • Fairfax, Virginia, United States, 22033
      • Inova Fair Oaks Hospital
    • Falls Church, Virginia, United States, 22042-3300
      • Inova Fairfax Hospital
    • Richmond, Virginia, United States, 23298-0037
      • Massey Cancer Center at Virginia Commonwealth University
  • Washington
    • Spokane, Washington, United States, 99210-0248
      • Deaconess Medical Center
    • Spokane, Washington, United States, 99204
      • Sacred Heart Medical Center
    • Spokane, Washington, United States, 99204
      • Associated Surgeons P.S.
    • Spokane, Washington, United States, 99208
      • Providence Cancer Center at Holy Family Hospital
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • Appleton Medical Center
    • Appleton, Wisconsin, United States, 54911-3454
      • Fox Valley Surgical Associates at Appleton Medical Center
    • Madison, Wisconsin, United States, 53792-7375
      • University of Wisconsin Comprehensive Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Memorial Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with adenocarcinoma of the colon or rectum.

Description

DISEASE CHARACTERISTICS:

• Diagnosis of stage I-III adenocarcinoma of the colon or rectum

• Must have undergone an initial curative resection within the past year

  • No colon or rectal cancer resection that does not allow for definitive T or N staging
  • No initial post-surgical surveillance colonoscopy prior to study entry
• Must have a pathology specimen, with representative normal and tumor tissues, available for submission to the ACOSOG Central Specimen Bank prior to study entry
• No personal or family history of familial adenomatous polyposis
• No recurrent colorectal cancer

PATIENT CHARACTERISTICS:

Age

• 18 to 49 at first diagnosis

Other

• Must be willing to provide a family cancer history to the study team and continue with follow-up colonoscopic surveillance
• No other malignancy within the past 5 years except completely resected cervical cancer or nonmelanoma skin cancer
• No evidence of recurrence of other prior malignancy

PRIOR CONCURRENT THERAPY:

Radiotherapy

• No prior pelvic radiotherapy for rectal cancer
• No concurrent preoperative pelvic radiotherapy for rectal cancer

Surgery

• See Disease Characteristics

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Group 1; Patients undergo baseline colonoscopy before or within 6 months of initial curative resection and then surveillance colonoscopy at 1, 3, and 5 years (+/- 6 months) after resection. The number, size, location, histology, and method of removal of polyps are documented at the time of colonoscopy. Patients also undergo microsatellite instability (MSI) status testing and complete family history questionnaires at baseline. The prognostic significance of family history and MSI status is evaluated. The individual histologic features of the tumors are compared with the MSI status to determine their predictive value. The histologic features are also correlated with outcome to determine their prognostic significance. Patients may be referred for genetic counseling.

Genetic: microsatellite instability analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival	Up to 2 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jose G. Guillem, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): December 1, 2004

Study Registration Dates

• First Submitted: September 6, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; adenocarcinoma of the colon; stage III colon cancer; stage II rectal cancer; stage III rectal cancer; stage II colon cancer; stage I rectal cancer; stage I colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: ACOSOG-Z0190; CDR0000069465 (Registry Identifier: NCI Physician Data Query)