Biomarkers for Early Detection of Colorectal Cancer in Adults Undergoing Colonoscopy
|Phase II||Biomarker/Laboratory analysis, Screening||Active||50 to 80||NCI||NCCTG-GLNE010|
GLNE 010, GLNE010, NCT01511653
- To determine if the sensitivity of stool vimentin methylation is greater than that for fecal immunochemical testing (FIT) for the detection of the combined endpoint of colorectal adenocarcinoma or adenomas with high-grade dysplasia, at the same specificity of stool vimentin methylation test.
- To estimate the sensitivity and specificity for colorectal adenocarcinoma and high-grade dysplasia, or screen relevant neoplasms (SRN) (colorectal adenocarcinoma, high-grade dysplasia, and adenomas ≥ 1 cm) of individual colorectal neoplasia early-detection biomarkers using colonoscopy as the gold standard.
- To estimate the sensitivity and specificity of the individual binary biomarkers (stool vimentin methylation, serum galectin-3 ligand, and the Exact Sciences stool DNA panel) in combination with FIT for colorectal adenocarcinoma and high-grade dysplasia, and for screen relevant neoplasms.
- To test the null hypothesis that the sensitivities of the combined tests described above are equal or lower than a minimally acceptable value (MAV) versus the alternative that they are higher than the MAV, with the MAV set as 70% for the detection of colorectal adenocarcinoma and high-grade dysplasia and 45% or higher for SRN, with fixed specificities.
- To construct a combined early-detection biomarker score of individual biomarkers (stool vimentin methylation, serum galectin-3 ligand, FIT and the Exact Sciences stool DNA panel) using logistic regression, and to describe its performance for colorectal adenocarcinoma, high-grade dysplasia, and SRN.
- To establish an archive of appropriately preserved stool, serum, plasma, and DNA human biospecimens to be used by Early Detection Research Network- (EDRN) approved investigators for future validation and biomarker discovery research.
- Adults 50-80 years of age undergoing a colonoscopy defined as:
- First-time screening or a surveillance procedure (colonoscopy cannot be for any therapeutic or diagnostic reason)
- No complete colon exam (colonoscopy or CT colonography) within 3 years
- No positive guiaiac-based occult blood or fecal immunochemical test (e.g., fecal occult blood test [FOBT] or fecal immunochemical testing [FIT] ) in the past 12 months
- No hereditary nonpolyposis colorectal cancer (HNPCC [Lynch syndrome]) or familial adenomatous polyposis (FAP)
- Has not undergone resection of the colon for any indication
- No complete colonoscopy within the past 3 years
- Prior flexible sigmoidoscopy allowed
- Able to physically tolerate removal of 34 mL of blood
- Willing to collect 2 stool samples
- No history of inflammatory bowel disease
- No overt rectal bleeding within 1 month (30 days) (including due to suspected hemorrhoids)
- No subjects with known HIV or chronic viral hepatitis (hepatitis B or C)
- No cancer within 5 years of enrollment except any of the following:
- Squamous cell carcinoma of the skin or 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
Sensitivity of stool vimentin methylation test greater than that for fecal immunochemical testing (FIT)
Sensitivity and specificity of the individual binary biomarkers
(stool vimentin methylation, serum galectin-3 ligand, and the Exact Sciences stool DNA
panel) in combination with FIT to detect colorectal adenocarcinoma, high-grade dysplasia, and relevant neoplasms
Sensitivities of the combined tests are equal or lower than a minimally acceptable value (MAV)
Combined biomarkers for early detection of colorectal adenocarcinoma, high-grade dysplasia, and relevant neoplasms
This is a multicenter study.
Participants undergo serum, plasma, and urine samples collection within 12 weeks prior to colonoscopy. Participants receive detailed instructions and complete kits to collect stool samples at home prior to beginning colon preparation procedures. They also receive detailed instructions on how to prepare the Fecal Immunochemical Test (FIT) tests. Participants then pack and ship the stools samples and the FIT test, per shipping instructions, to the Central Biosample Laboratory at the University of Michigan using a pre-paid Department of Transportation-compliance packaging. Participants with detectable colorectal adenocarcinoma, high-grade dysplasia, and adenomas at the time of colonoscopy undergo tissue sample collection.
Samples are analyzed for presence of methylated vimentin gene, fecal immunochemical test, galectin-3 ligand, DNA panel of genetic biomarker and other unspecified biomarkers by qualitative tests, FOBT-CHEKoc®, ELISA, qInvader (multiplexed rtPCR assay), and immuno-hemoglobulin (ELISA-based) assay.
Patients complete the NIH Health Diet Health II Food Frequency Questionnaire, the Early Detection Research Network (EDRN) demographic, and medical history questionnaires at baseline.
After completion of colonoscopy, patients are followed up by telephone, e-mail, or letter for 1 year.
Trial Lead Organizations
North Central Cancer Treatment Group
|Charles Loprinzi, MD, Principal investigator|
|Cancer Research Center of Hawaii|
|Clinical Trials Office - Cancer Research Center of Hawaii|
|Tripler Army Medical Center|
|Jeffrey Berenberg, MD|
|Louis A. Weiss Memorial Hospital|
|Clinical Trials Office - Louis A. Weiss Memorial Hospital|
|CCOP - Carle Cancer Center|
|Clinical Trials Office - CCOP - Carle Cancer Center|
|CCOP - Wichita|
|Shaker Dakhil, MD, FACP|
|CCOP - Grand Rapids|
|William Beaumont Hospital - Royal Oak Campus|
|Clinical Trials Office - William Beaumont Hospital - Royal Oak Campus|
|CCOP - Duluth|
|Roswell Park Cancer Institute|
|Clinical Trials Office - Roswell Park Cancer Institute|
|SUNY Upstate Medical University Hospital|
|Clinical Trials Office - SUNY Upstate Medical University Hospital|
|Preston Steen, MD|
|Middletown Regional Hospital|
|Cancer Care Associates - Mercy Campus|
|Vikki Canfield, MD|
|Natalie Warren Bryant Cancer Center at St. Francis Hospital|
|Gibbs Regional Cancer Center at Spartanburg Regional Medical Center|
|Clinical Trials Office - Gibbs Regional Cancer Center|
|Sanford Cancer Center at Sanford USD Medical Center|
|Clinical Trials Office - Sanford Cancer Center|
|St. Vincent Hospital Regional Cancer Center|
|Clinical Trials Office - St. Vincent Hospital Regional Cancer Center|
|Gundersen Lutheran Center for Cancer and Blood|
|Clinical Trials Office - Gundersen Lutheran Cancer Center|
|Marshfield Clinic - Marshfield Center|
|Clinical Trials Office - Marshfield Clinic - Marshfield Center|
|Official Title||Validation and Comparison of Biomarkers for the Early Detection of Colorectal Adenocarcinoma|
|Trial Start Date||2012-04-23|
|Trial Completion Date||2012-09-30 (estimated)|
|Registered in ClinicalTrials.gov||NCT01511653|
|Date Submitted to PDQ||2011-07-11|
|Information Last Verified||2013-05-24|
|NCI Grant/Contract Number||CA86400-11|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.