Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas

• ClinicalTrials.gov Identifier: NCT00843375
• Recruitment Status: Recruiting
• First Posted: February 13, 2009
• Last Update Posted: January 30, 2024
• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: Early Detection Research Network; Clinical Genomics Pathology; VolitionRx; Department of Health and Human Services; Great Lakes New England Clinical Validation Center; National Cancer Institute (NCI)
• Information provided by (Responsible Party): University of Michigan Rogel Cancer Center

Study Description

Brief Summary:

Colon cancer is the second most common cancer in men and women. It is a disease that can be prevented if it is found early. Colonoscopy is still the best screening tool for colon cancer and the polyps that turn into colon cancer. However, due to a variety of factors, including affordability, time, and age, not all patients are able to be screened. Researchers are working on other options for early detection that are as accurate as colonoscopy.

The purpose of this study if to determine if stool or blood can be used to detect colon cancers as early or earlier than colonoscopy. The researchers plan to use these samples to learn about specific proteins (also known as biomarkers) that may indicate colon polyps, colon cancer or an increased risk of developing colon cancer. In order to learn more about preventing and detecting colon and rectal cancer, we are collecting samples from subjects with cancer, adenomas, and colonoscopies who may be at risk for polyps.

Condition or disease
Colonic Neoplasms

Detailed Description:

In recognition of the fact that novel potential biomarkers are continually being identified and will need to be validated in a rapid, efficient and scientifically rigorous manner, the NCI has made an enormous commitment to the development of a network that will facilitate biomarker development and validation in multiple organ sites. As part of the National Cancer Institute-funded Early Detection Research Network (EDRN), the Great Lakes-New England Clinical Epidemiological Center (GLNE CEC) proposes a research study that validates potential molecular markers ("biomarkers") for the detection of precancerous and cancerous conditions and cancer risk assessment. Although examples of such biomarkers are currently in clinical use (i.e. CEA, CA-125), there are limitations to all of them. Our consortium focuses on gastrointestinal neoplasia. The goals of this phase of the proposed research are:

1. Assessment of the utility of individual stool-based, serum-based and urine-based biomarkers for discriminating between patients with adenocarcinomas, patients with adenomas, patients without adenomas and normal subjects both at normal and high risk for developing colon cancer.

2. Construction of a panel of markers from those considered in Objective 1 to discriminate, under a number of assumptions concerning prevalence and cost of misclassification, between:

   1. Subjects with normal colons versus patients without adenomas, patients with adenomas and patients with cancers;
   2. Subjects with normal colons, patients without adenomas and patients with adenomas, versus subjects with cancers;
   3. Subjects with normal colons versus patients without and patients with adenomas versus patients with cancers.
3. Comparison of the characteristics of individual markers and panels as discriminators to those of the established current standard, fecal immunochemical test (FIT).
4. Continued support of a renewal of a bank of stool samples linked to serum, tissue, and clinical data from patients with colorectal cancer, adenomas and normal controls for validation of stool-based markers that may be developed in the future.

To build our collection, we propose to collect stool, FIT, serum, plasma, and tissue samples from 1200 new subjects. Each biomarker will be analyzed individually and considered as a potential panel marker to be used for future largescale screening longitudinal trials. (This protocol previously recruited an additional 682 subjects from January 2006 to June 2010.)

Study Design

• Study Type: Observational
• Estimated Enrollment: 1200 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas
• Actual Study Start Date: August 7, 2019
• Estimated Primary Completion Date: March 2028
• Estimated Study Completion Date: March 2028

Groups and Cohorts

Group/Cohort
Higher risk, no neoplasia; Negative study colonoscopy and one or more of the following: Subjects with a personal history of adenomas (confirmed by pathology) with none present on qualifying colonoscopy; Subjects with a personal history of colorectal cancer (CRC) (longer than 3 years ago because of exclusion criteria of cancer within last 3 years) with none present at time of qualifying colonoscopy; Any family history of CRC (1st degree relative); Current positive screening stool test for blood, for DNA or for both within 12 months with no follow up intervention
Adenoma; Pathologically confirmed adenomas, both non-advanced adenoma and advanced. Advanced adenoma includes any of the following: Sessile serrated adenoma; Tubulovillous adenoma; Villous adenoma; Sessile serrated polyp/adenoma; Traditional serrated adenoma; Any adenoma ≥1 cm
Colorectal adenocarcinoma; Pathologically confirmed colorectal cancer either present at time of stool collection or discovered during colonoscopy
Average risk, no neoplasia; No neoplasia found at colonoscopy and: No prior history of adenomas or sessile serrated adenomas; No prior history of CRC; No first degree family history of CRC; Negative colorectal cancer screening test (if performed) for blood, for DNA or for both within 12 months.

Outcome Measures

Primary Outcome Measures :

1. Biospecimen Retention: Samples with DNA [ Time Frame: At 1 day of biospecimen collection ]
   Blood samples, up to 60 mls, will be obtained according to standard operating procedures. Subjects will collect stool samples per the schedule in the study calendar. Collection of Frozen Normal and Adenoma or Cancer Tissue: For individuals with large adenomas who are undergoing endoscopic resection, the fresh surgical sample will be obtained by the endoscopist.

Biospecimen Retention:   Samples With DNA

Blood samples, up to 60 mls, will be obtained according to standard operating procedures. Subjects will collect stool samples per the schedule in the study calendar. Collection of Frozen Normal and Adenoma or Cancer Tissue: For individuals with large adenomas who are undergoing endoscopic resection, the fresh surgical sample will be obtained by the endoscopist.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with colorectal cancer and adenomas and scheduled for surgical or endoscopic resection or subjects scheduled for a colonoscopy will be recruited from collaborating consortium centers.

Criteria

Inclusion Criteria:

• Willing to sign informed consent
• Able to physically tolerate removal of up to 60 ml of blood
• Adults at least 18 years old
• Willing to collect 1-2 stool samples and prepare a Fecal Immunochemical Test (FIT)
• Pregnant or nursing women who otherwise meet the eligibility criteria may participate

• Subjects with one of the following:

  • Colorectal adenocarcinoma-not treated and in colon at time of stool collection (CRC bin)
  • Adenoma-pathologically confirmed adenoma present in colon at time of stool collection (Adenoma Bin)

  • Higher Risk Non-neoplastic Bin

    • Subjects with a personal history of adenomas (confirmed by pathology) with none present on qualifying colonoscopy
    • Subjects with a personal history of CRC (longer than 3 years ago because of exclusion criteria of cancer within last 3 years) with none present at time of qualifying colonoscopy
    • Any family history of CRC (1st degree relative)
    • Current positive screening stool test for blood, for DNA or for both within 12 months with no follow-up intervention.

  • Average Risk, Non-neoplastic Bin

    • No history or current finding of any colorectal neoplasia including CRC, adenomas, sessile serrated adenomas and no family history of CRC.
    • Subjects who had CRC that was successfully treated at least three years ago may be considered eligible for the adenoma bin if their polyps are adenomas and there is no evidence of CRC, or for the higher risk non-neoplastic bin as noted above.

    • Subjects whose screening colonoscopy shows any of these types of polyps may be included in the non-neoplastic or the higher risk non-neoplastic bin if they meet the other criteria noted above.

      • Hyperplastic polyps
      • Benign mucosal polyps
      • Polypoid granulation tissue
      • Prolapsed mucosal polyps
      • Inflammatory polyp
      • Transitional mucosal polyp
      • Lipoma
      • Gangleoneuroma
      • Neuroma
      • Hamartomatous polyp

Exclusion Criteria:

• Cancer patients who have had any surgery, radiation, or chemotherapy for their current colorectal cancer prior to collecting the baseline samples
• History of or clinically active Inflammatory Bowel Disease
• Known HNPCC or FAP
• Inability to provide informed consent.

• Other active malignancy within 3 years of enrollment except any of the following:

  • Squamous cell carcinoma of the skin
  • Basal cell carcinoma of the skin
  • Carcinoma in situ of the cervix, Stages Ia or Ib invasive squamous cell carcinoma of the cervix treated by surgery only. (Excluded if had pelvic radiation)
  • Stage Ia Grade 1 adenocarcinoma of the endometrium treated with surgery
• Patients on active chemotherapy or radiation treatment for any purpose
• Known HIV or chronic active viral hepatitis
• Women who are pregnant
• CT colonography (virtual colonoscopy) patients

Contacts and Locations

Contacts

Contact: Cancer AnswerLine; 1-800-865-1125; CancerAnswerLine@med.umich.edu

Locations

United States, Massachusetts

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator: Sapna Syngal, MD

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Cancer AnswerLine 800-865-1125 CancerAnswerLine@med.umich.edu

Principal Investigator: Elena Stoffel, MD

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Principal Investigator: Tim Church, MD

United States, New York

NYU Langone Health; Recruiting

New York, New York, United States, 10016

Contact: Aasma Shaukatr, MD 212-686-2500 Shaukat@nyulangone.org

Contact: Jessica Rauch 646-501-9624

Principal Investigator: Aasma Shaukat, MD

United States, North Carolina

University of North Carolina; Recruiting

Chapel Hill, North Carolina, United States, 27599

Principal Investigator: John Barron, MD

United States, Pennsylvania

Hershey Medical Center; Recruiting

Hershey, Pennsylvania, United States, 17033

Principal Investigator: Mack Ruffin, MD

United States, Texas

M.D. Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Principal Investigator: Robert Bresalier, MD

United States, Washington

University of Washington; Recruiting

Seattle, Washington, United States, 98195

Principal Investigator: William Grady, MD

Australia, South Australia

Flinders Medical Center; Recruiting

Adelaide, South Australia, Australia, 5001

Principal Investigator: Graeme Young, MD, MBBS

Canada, Ontario

St. Michael's Hospital; Not yet recruiting

Toronto, Ontario, Canada

Principal Investigator: Norman Marcon, MD

Sponsors and Collaborators

University of Michigan Rogel Cancer Center

Early Detection Research Network

Clinical Genomics Pathology

VolitionRx

Department of Health and Human Services

Great Lakes New England Clinical Validation Center

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Dean E Brenner, M.D.; University of Michigan

More Information

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT00843375
• Other Study ID Numbers: UMCC 2018.126 GLNE 007; U01CA086400 ( U.S. NIH Grant/Contract ); HUM00149961 ( Other Identifier: University of Michigan ); UMCC 2018.126 ( Other Identifier: University of Michigan ); HUM00029506 ( Other Identifier: University of Michigan ); UMCC 2005.008 ( Other Identifier: University of Michigan ); HUM00161344 ( Other Identifier: University of Michigan )
• First Posted: February 13, 2009
• Last Update Posted: January 30, 2024
• Last Verified: January 2024

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenoma; Colonic Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type