Biomarkers for Early Detection of Colorectal Cancer in Adults Undergoing Colonoscopy
This clinical trial studies biomarkers for early detection of colorectal cancer in participants undergoing colonoscopy. Studying samples of blood, stool, and urine from participants undergoing colonoscopy in the laboratory may help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify biomarkers related to cancer.
Inclusion Criteria
- Adults undergoing a colonoscopy defined as:
- Group A (50-59 first time colonoscopy) * Adults 50-59 * First time colonoscopy for screening indication
- Group B (60-69 screening colonoscopy) * Adults 60-69 * Prior complete colon exam but no complete colon exam (colonoscopy or computed tomography [CT] colon) within 9 years (108 months)
- Group C (60+ first time colonoscopy) * Adults 60 and older * No complete colon exam (colonoscopy or CT colon) ever
- Group D (70+ screening colonoscopy) * Adults 70 and older * Prior complete colon exam but no complete colon exam (colonoscopy or CT colon) within 9 years (108 months)
- Group E (70+ surveillance colonoscopy) * Adults 70 and older * Colonoscopy indicated for personal history of adenomas, any interval since prior complete colon exam (colonoscopy or CT colon)
- Group F (50-69 surveillance colonoscopy) * Ages 50-69 * Prior complete colon exam with ONE or more of the following findings and have pathology report of lesion available for confirmation: ** Prior 3-10 tubular adenomas: no colonoscopic exam within 3 years ** Prior > 10 adenomas: no colonoscopic exam within 3 years ** Prior one or more tubular adenomas >= 10 mm: no colonoscopic exam within 3 years ** Prior one or more villous (or tubulovillous) adenomas: no colonoscopic exam within 3 years ** Prior adenoma with high grade dysplasia: no colonoscopic exam within 3 years ** Sessile serrated polyp(s) < 10 mm with no dysplasia: no colonoscopic exam within 3 years ** Sessile serrated polyp(s) >= 10 mm OR sessile serrated polyp with dysplasia OR traditional serrated adenoma: no colonoscopic exam within 3 years
- Willing to sign informed consent
- Able to physically tolerate removal of about 41 mL of blood
- Willing to collect 2 stool samples
- Meet the requirements for one of the eligibility groups
Exclusion Criteria
- Inability to provide informed consent
- History of inflammatory bowel disease
- Overt rectal bleeding within 1 month (30 days) (including due to suspected hemorrhoids)
- Positive guaiac-based occult blood or fecal immunochemical test (e.g., fecal occult blood test [FOBT], FIT) in the past 12 months (365 days)
- Undergone resection of the colon for any indication
- Subjects with known human immunodeficiency virus (HIV) or chronic viral hepatitis (hepatitic B and C)
- Subjects with known or suspected hereditary nonpolyposis colorectal cancer (HNPCC) (Lynch syndrome) or familial adenomatous polyposis (FAP)
- Any cancer within 5 years prior to enrollment except squamous cell carcinoma of the skin or basal cell carcinoma of the skin; no prior history of colon cancer or rectal cancer
- Subjects ages 50-69 with a prior complete colon exam (colonoscopy or CT colon) with an interval since last colonoscopy AND * Does not meet criteria in Group B or Group F
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01511653.
PRIMARY OBJECTIVES:
I. To estimate the sensitivity and specificity for 1) colorectal adenocarcinoma and
high grade dysplasia, or 2) screen relevant neoplasms (SRN) (colorectal adenocarcinoma,
high grade dysplasia, and adenomas >= 1 cm) of the following individual colorectal neoplasia early detection biomarkers using colonoscopy as the gold standard: stool vimentin methylation, serum galectin-3 ligand, fecal immunochemical tests (FIT), exact sciences stool DNA panel, other currently unspecified biomarkers.
II. 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.
III. 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 1) colorectal adenocarcinoma and high-grade dysplasia, and for 2) screen relevant neoplasms.
IV. 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.
V. To construct a combined early-detection biomarker score using the above individual biomarkers (stool vimentin methylation, serum galectin-3 ligand, FIT and the exact sciences stool DNA panel) using logistic regression, and describe its performance for 1) colorectal adenocarcinoma and high-grade dysplasia, and for 2) SRN.
VI. 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.
OUTLINE:
Participants undergo serum, plasma, and urine samples collection within 16 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 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®, and ELISA. 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 for 1 year.
Trial PhasePhase II
Trial Typescreening
Lead OrganizationAlliance for Clinical Trials in Oncology
Principal InvestigatorDean E Brenner
- Primary IDGLNE 010
- Secondary IDsNCI-2012-00679, GLNE010, CDR0000703565, NCCTG-GLNE010
- ClinicalTrials.gov IDNCT01511653