Gene Testing in Patients With Colon Cancer

Tumor Replication Error (RER) Status and Outcome in a Colon Cancer Adjuvant Chemotherapy Trial

RATIONALE: Analyzing the structure of genes found in a person's cancer cells may help doctors improve methods of treating patients with colon cancer.

PURPOSE: Clinical trial to study the genes of patients treated with chemotherapy for colon cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Genetic: mutation analysis; Genetic: tumor replication error analysis

Detailed Description

OBJECTIVES:

• Determine the relationship between disease free survival, overall survival, and tumor replication error status for patients who have received adjuvant chemotherapy for colon cancer on CALGB protocol 8896.
• Determine the prognostic and predictive values for response to this therapy in these patients.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-1996
      • Veterans Affairs Medical Center - Birmingham
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego Cancer Center
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center - San Francisco
    • San Francisco, California, United States, 94143-0128
      • UCSF Cancer Center and Cancer Research Institute
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center
  • Florida
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago (Westside Hospital)
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
  • Iowa
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center at the University of Iowa
  • Maine
    • Togus, Maine, United States, 04330
      • Veterans Affairs Medical Center - Togus
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Veterans Affairs Medical Center - Minneapolis
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Veterans Affairs Medical Center - Columbia (Truman Memorial)
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center - Columbia
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198-3330
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Medical Center - Buffalo
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • Schneider Children's Hospital at North Shore
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital - Cornell Campus
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center, NY
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
    • Syracuse, New York, United States, 13210
      • Veterans Affairs Medical Center - Syracuse
    • Syracuse, New York, United States, 13217
      • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Durham, North Carolina, United States, 27705
      • Veterans Affairs Medical Center - Durham
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27104-4241
      • CCOP - Southeast Cancer Control Consortium
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital - Ohio State University
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • University of Tennessee, Memphis Cancer Center
    • Memphis, Tennessee, United States, 38104
      • Veterans Affairs Medical Center - Memphis
  • Vermont
    • White River Junction, Vermont, United States, 05009
      • Veterans Affairs Medical Center - White River Junction
  • Virginia
    • Richmond, Virginia, United States, 23298-0037
      • MBCCOP - Massey Cancer Center
    • Richmond, Virginia, United States, 23249
      • Veterans Affairs Medical Center - Richmond

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 previously enrolled on CALGB-8896.

Description

DISEASE CHARACTERISTICS:

• Patients who received chemotherapy for colon cancer as part of CALGB protocol 8896
• Underwent an initial resection for adenocarcinoma of the colon and were determined to have a high risk of tumor recurrence based upon nodal disease or local extension of tumor with obstruction or perforation due to tumor
• Surgical specimen blocks available, including tumor tissue and normal tissue

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
Samples of tumor and normal tissue; Samples of tumor and normal tissue are obtained from CALGB 8896 patients. The samples are tested for somatic mutations and tumor replication error (RER) tumor status. Patients do not receive the results of the genetic testing and the results do not influence the type or duration of treatment.	Genetic: mutation analysis; Genetic: tumor replication error analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
disease free survival	Up to 10 years

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	Up to 10 years
tumor replication error status	Up to 10 years
determine the prognostic and predictive values for response to this therapy	Up to 10 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Monica M. Bertagnolli, MD, Dana-Farber/Brigham and Women's Cancer Center

Publications and helpful links

General Publications

• Goel A, Arnold CN, Niedzwiecki D, Carethers JM, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR. Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res. 2004 May 1;64(9):3014-21. doi: 10.1158/0008-5472.can-2401-2.
• Goel A, Arnold CN, Niedzwiecki D, Chang DK, Ricciardiello L, Carethers JM, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR. Characterization of sporadic colon cancer by patterns of genomic instability. Cancer Res. 2003 Apr 1;63(7):1608-14.
• Arnold CN, Goel A, Compton C, Marcus V, Niedzwiecki D, Dowell JM, Wasserman L, Inoue T, Mayer RJ, Bertagnolli MM, Boland CR. Evaluation of microsatellite instability, hMLH1 expression and hMLH1 promoter hypermethylation in defining the MSI phenotype of colorectal cancer. Cancer Biol Ther. 2004 Jan;3(1):73-8. doi: 10.4161/cbt.3.1.590. Epub 2004 Jan 5.
• Goel A, Arnold CN, Tassone P, Chang DK, Niedzwiecki D, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR. Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers. Int J Cancer. 2004 Dec 10;112(5):754-9. doi: 10.1002/ijc.20472.

Study record dates

Study Major Dates

• Study Start: August 1, 1998
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: July 14, 2003
• First Posted (Estimate): July 15, 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 colon; stage III 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; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: CALGB-9865; U10CA031946 (U.S. NIH Grant/Contract); CLB-9865; CDR0000066637 (Registry Identifier: NCI 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