Combining Risk Factors and Faecal Immunochemical Testing in Colorectal Cancer Screening: a Randomized Controlled Trial

NCT04490551 | Completed

• 1 other identifier: AMC_MDL_161
• Study Type: interventional
• Target: 6,753
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal Carcinoma (CRC) is the third most frequent diagnosed cancer worldwide, with 1.4 million new cases every year. In an attempt to reduce this number many countries have implemented a nationwide screening programme targeted at detecting CRC in an early phase using fecal immunochemical tests (FITs). People with an elevated level of blood in their stool are offered a colonoscopy, an invasive medical procedure where CRCs and premalignant lesions (together also referred to as advanced neoplasia) can be detected accurately. However, the current screening method using FIT is not optimal. In FIT-based CRC screening studies, 1 in 4 participants with CRC and 2 in 3 participants with advanced neoplasia receive a negative FIT result. In contrast, an estimated 1 in 2 FIT-positives have advanced neoplasia at colonoscopy. Recent studies have demonstrated that a risk model that takes into account the FIT result and other risk factors for CRC could enhance the effectiveness of a FIT-based CRC screening programme. The objective of this study is to assess the yield of advanced neoplasia in the colon and rectum of a FIT-based risk model at colonoscopy, compared to that of a FIT-only CRC screening strategy. Our hypothesis is that a risk-based model yields significantly more advanced neoplasia at colonoscopy than the FIT by itself, and that it does not affect participation rate. To assess this hypothesis, the investigators have designed a clinical trial in which the investigators randomize 23,000 asymptomatic individuals between the age of 55 and 75 years old to either risk-based screening (intervention group) or FIT-only screening (control group). The intervention group will receive a questionnaire on risk factors of CRC (e.g. smoking, family history of CRC), and a FIT. The control group will only receive the FIT. The positivity threshold of the FIT in both groups will be set at 15 micrograms haemoglobin per gram faeces. The positivity threshold of the risk-based model in the intervention group will be set at 0.10 (out of a range of 0 to 1), a threshold that is calculated with a goal to match the positivity rate of the control group. Participants with a result that is above the thresholds of the FIT and/or the risk-based model will be invited to undergo a colonoscopy according protocol of the Dutch national screening program. After the study has ended, the investigators will compare both groups to assess our hypotheses.

Conditions

Colorectal Cancer; Colorectal Carcinoma; Colorectal Neoplasms; Colorectal Adenoma; Colorectal Adenoma and Carcinoma

Keywords

Colorectal Cancer; Screening; Model; Faecal Immunochemic Test; FIT; Occult Blood; Risk Factors; Logistic Regression; Advanced Neoplasia; Advanced Adenoma

Outcome Measures

Primary Outcomes (1)

• Yield of Advanced Neoplasia

  The primary outcome is the yield of advanced neoplasia, defined as the relative number of invitees in whom advanced neoplasia is detected at colonoscopy.

  10 weeks

Secondary Outcomes (4)

• Standardized Screening Yield

  10 weeks

• Participation Rate

  10 weeks

• Yield of Advanced Neoplasia at Other Thresholds

  10 weeks

• Yield of Proximally Located Advanced Neoplasia

  10 weeks

Study Arms (2)

Intervention group

EXPERIMENTAL

This group will be screened with the risk-based model. The input of the model will be gathered with the FIT, a validated questionnaire, and from data of the Dutch general population registry. The threshold of the model will be set at a calculated risk of 0.10. To comply with ethical guidelines, all participants in this group with a FIT result of \>=15 mcg Hb/g faeces and a calculated risk of \<0.10 will also be offered a colonoscopy.

Diagnostic Test: Risk-based logistic regression model; Diagnostic Test: FIT

Control group

ACTIVE COMPARATOR

This group will be screened with the FIT. The threshold of the FIT will be set at \>= 15 mcg Hb/g faeces.

Diagnostic Test: FIT

Interventions

Risk-based logistic regression model DIAGNOSTIC_TEST

The intervention will be a risk-based logistic regression model that takes multiple variables into account to calculate the risk of advanced neoplasia as an outcome.

Intervention group

FIT DIAGNOSTIC_TEST

FIT is a stool-based test that detects human blood in faeces.

Also known as: Faecal Immunochemic Test

Control group; Intervention group

Eligibility Criteria

• Age: 55 Years - 75 Years
• Gender Eligibility Details: Male and Females
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, a screening invitee must meet the following criteria:
• The screening invitee must be at least 55 years old, and no older than 75 years old, at the day of invitation by the Foundation of Population Screening Mid-West
• The screening invitee must be eligible for participation in the second round of the Dutch CRC Population Screening Programme
• The screening invitee must return a signed informed consent form

You may not qualify if:

• A potential screening invitee who meets any of the following criteria will be excluded from participation in this study:
• if he or she receives active treatment for CRC and/or AN, including palliative care.
• if he or she fails to return a sample that is adequate for FIT testing.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC, locatie Academisch Medisch Centrum

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

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MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Evelien Dekker, PhD MD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The researchers conduct a parallel group randomized controlled trial. Asymptomatic individuals will be randomized to either risk-based screening or FIT-only screening.

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 29, 2020
• Study Start: December 5, 2019
• Primary Completion: December 31, 2020
• Study Completion: June 1, 2021
• Last Updated: August 13, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)