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

Tracking Information

• First Submitted Date: February 12, 2009
• First Posted Date: February 13, 2009
• Last Update Posted Date: January 30, 2024
• Actual Study Start Date: August 7, 2019
• Estimated Primary Completion Date: March 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2020)

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.

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas
• Official Title: Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas

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.

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 Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

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.

• 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.
• Condition: Colonic Neoplasms
• Intervention: Not Provided

Study Groups/Cohorts

• 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.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 23, 2021): 1200
• Original Estimated Enrollment (submitted: February 12, 2009): 800
• Estimated Study Completion Date: March 2028
• Estimated Primary Completion Date: March 2028 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Australia, Canada, United States
• Removed Location Countries: Puerto Rico

Administrative Information

• NCT Number: 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Michigan Rogel Cancer Center
• Original Responsible Party: Dr. Dean Brenner, MD, Professor of Internal Medicine, University of Michigan
• Current Study Sponsor: University of Michigan Rogel Cancer Center
• Original Study Sponsor: University of Michigan

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)

Investigators

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

• PRS Account: University of Michigan Rogel Cancer Center
• Verification Date: January 2024