Non-invasive Risk Stratification of CR AMN/SSP (FIT)

Professor Michael Bourke

Status: Terminated

Conditions: Adenomatous Polyps

Treatments: Other: blood or stool samples will be collected

Study type: Observational

Funder types: Other

Identifiers

NCT02476682

HREC2014/9/4.4(4079)

Details and patient eligibility

About

The purpose of this study is to determine the clinical utility of stool and blood methylation tests for detection of advanced mucosal neoplasia (AMN) and sessile serrated polyps (SSP).

Full description

By not only diagnosing colorectal cancer (CRC) at an early stage, but also removing precursor lesions (adenomas), colonoscopy with polypectomy reduces the risk of developing and dying from CRC. Approximately 90% of polyps are less than 10 mm and are easily removed by competent endoscopists. Laterally spreading lesions (LST) and sessile lesions of the colon, also known as advanced mucosal neoplasia (AMN) are underrecognised types of lesions that are more likely to progress to cancer. They include sessile serrated polyps (SSP), an emerging entity of flat polyps with malignant potential. Detection of hemoglobin (a component of blood) in stool is an established validated screening tool for CRC. Its specific role in the prediction of AMN, and particularly SSPs is yet to be defined. Blood tests measuring the level of tumour derived methylated deoxyribonucleic acid (DNA) in blood circulating have been demonstrated to have clinical utility for detection of CRC and AMN. A blood based CRC screening test has the potential to increase compliance. This study aims to determine the clinical utility of stool and blood methylation tests for detection of AMN and SSPs. Stool and blood will be obtained from consenting patients referred for endoscopic removal of known ANM and SSP (study arm) as well as from consenting patients scheduled for colonoscopy screening (control arm). The level of stool hemoglobin and methylated tumour derived DNA in circulation will be measured in the two study groups. Cutoff values will be generated to assess best predictive capability of high risk lesions based on these tests.

Enrollment: 205 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Individuals capable and willing of proving satisfactory informed consent
• Individuals with colonic lesions larger than 20mm
• Individuals diagnosed with laterally spreading or sessile polyp morphology
• Individuals schedules for screening colonoscopy and with no prior history of CRC
• Ability and willingness to collect stool sample at home
• Ability and willingness to undergo venepuncture procedure

Exclusion criteria

• Individuals not able or unwilling to provide informed consent
• Individuals less than 18 year of age
• Individuals who undergo an incomplete colonoscopy or resection, which raises doubt as to the status of the colon (post-hoc exclusion)
• Individuals with a prior history of CRC
• Individuals with a history of Irritable Bowel Disease (IBD), hereditary nonpolyposis colorectal cancer (HNPCC) or Familial adenomatous polyposis (FAP)
• Individuals with bleeding diathesis
• Pregnancy

Trial design

205 participants in 6 patient groups

Normal subjects

Description:

blood or stool samples will be collected from people referred for screening colonoscopy

Treatment:

Other: blood or stool samples will be collected

Colorectal cancer

Description:

blood or stool samples will be collected from people with colorectal cancer detected at colonoscopy or resection

Treatment:

Other: blood or stool samples will be collected

Polyps <10mm and no high risk features

Description:

blood or stool samples will be collected from people with no polyps or low risk polyps (\<10mm, no villous component or dysplasia) detected at colonoscopy

Treatment:

Other: blood or stool samples will be collected

Advanced Mucosal Neoplasia

Description:

blood or stool samples will be collected from people with AMN detected at resection

Sessile Serrated Adenoma

Description:

blood or stool samples will be collected from people with SSP detected at resection

non-colorectal neoplastic disease

Description:

Participants with disease that is not colorectal neoplasia. Analysis of this cohort is not a primary endpoint but the investigators will report assay positivity in this group on an opportunistic basis. This cohort will include patients diagnosed with, for example, inflammatory bowel disease or extracolonic cancer.

Treatment:

Other: blood or stool samples will be collected