Genetic Markers in Patients With Colorectal Cancer

Clinical Significance of Genetic Markers in Colon Cancer

RATIONALE: Determination of genetic markers for colorectal cancer may improve the identification of patients who are at highest risk for relapse.

PURPOSE: This clinical trial is studying the importance of genetic markers for detecting relapse in patients with colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Genetic: DNA stability analysis; Genetic: loss of heterozygosity analysis; Genetic: microsatellite instability analysis

Detailed Description

OBJECTIVES:

• Determine the clinical and pathologic significance of unstable DNA elements in colorectal cancer (tumor microsatellite instability).
• Determine the clinical and pathologic significance of loss of heterozygosity for chromosomes 5, 8, 17, and 18 (as the primary targets) and of chromosomes 1, 14, and 22 (as the secondary targets) in colorectal cancer.

OUTLINE: DNA is examined for unstable elements (microsatellite instability and loss of heterozygosity) by analyzing at least 10 separate (CA)n-repeats localized to 5 separate chromosomes (5q, 8p, 15, 17p, and 18q). Loss of heterozygosity is analyzed for at least four chromosomal arms (5q, 8p, 17p, and 18q) and later other chromosomes (e.g., 1, 14, and 22). Immunohistochemistry is used to test for the presence or absence of the genes involved in DNA mismatch repair (hMLH1 and hMSH2).

Patients do not receive the results of the genetic testing and the results do not influence the type or duration of treatment.

PROJECTED ACCRUAL: This study will accrue up to 708 specimens.

• Study Type: Observational
• Enrollment (Actual): 675

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5404
      • CCOP - Mayo Clinic Scottsdale Oncology Program
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients have resectable adenocarcinoma of the colon or rectum and has been previously enrolled on N784852, N794604, N844652, N864751, N874651, and N894651.

Description

DISEASE CHARACTERISTICS:

• Must have had a resectable adenocarcinoma of the colon or rectum and must have participated in one of the following NCCTG randomized clinical trials:

  • 784852: No Treatment Control Versus Levamisole Versus Levamisole Plus Fluorouracil (5-FU)
  • 794604: No Treatment Control Versus 5-FU by Portal Vein Infusion
  • 794751: Postoperative Radiation Versus Postoperative Radiation Plus Sequential Chemotherapy with Methyl CCNU and 5-FU
  • 844652: An Intergroup Study - An Evaluation of Levamisole Plus 5-FU as Surgical Adjuvant Treatment for Resectable Adenocarcinoma of the Colon
  • 864751: Phase III Protocol for Surgical Adjuvant Therapy of Rectal Carcinoma: A Controller Evaluation of (A) Protracted-Infusion 5-FU as a Radiation Enhancer and (B) 5-FU Plus Methyl-CCNU Chemotherapy
  • 874651: M/N - A Controller Evaluation of Recombinant Interferon-gamma (IFL GM) and 5-FU and Folinic Acid With or Without Levamisole as Adjuvant Treatment for Resectable Adenocarcinoma of the Colon
  • 894651: A Controller Phase III Evaluation of 5-FU Combined With Levamisole and Leucovorin as Adjuvant Treatment for Resectable Colon Cancer
• Tissue blocks from the primary colorectal cancer must have been received by the NCCTG operations office

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Group 1; DNA is examined for unstable elements (microsatellite instability and loss of heterozygosity) by analyzing at least 10 separate (CA)n-repeats localized to 5 separate chromosomes (5q, 8p, 15, 17p, and 18q). Loss of heterozygosity is analyzed for at least four chromosomal arms (5q, 8p, 17p, and 18q) and later other chromosomes (e.g., 1, 14, and 22). Immunohistochemistry is used to test for the presence or absence of the genes involved in DNA mismatch repair (hMLH1 and hMSH2). Patients do not receive the results of the genetic testing and the results do not influence the type or duration of treatment.

Genetic: DNA stability analysis; Genetic: loss of heterozygosity analysis; Genetic: microsatellite instability analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the clinical and pathologic significance of unstable DNA elements	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the clinical and pathologic significance of loss of heterozygosity	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003 Jul 17;349(3):247-57. doi: 10.1056/NEJMoa022289.

Study record dates

Study Major Dates

• Study Start: September 1, 1997
• Primary Completion (Actual): July 1, 2003
• Study Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: April 10, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 13, 2016
• Last Update Submitted That Met QC Criteria: July 12, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: rectal cancer; 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: NCCTG-934655; CDR0000065549 (Registry Identifier: PDQ (Physician Data Query))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No