NORCCAP: Norwegian Colorectal Cancer Prevention Trial

Study Overview
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Brief Summary
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The purpose of this study is to see if screening with flexible sigmoidoscopy (a flexible viewing tube) may reduce large bowel cancer and cancer deaths. The researchers also want to see if the addition of screening for occult blood in stools may contribute further to this aim. Additionally, the researchers also want to see to which extent (and in which direction) the study may influence overall endoscopic activity in the general population in the screening area and in areas where controlled screening is not established.

Detailed Description
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Although flexible sigmoidoscopy (FS) as a screening tool has a much higher test sensitivity than fecal occult blood tests (FOBT) for colorectal cancer and high-risk adenomas, randomised trials with long-term follow-up are missing. The primary aim is to evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions (polypectomy of adenomatous polyps) Secondary aims: Evaluation of cost/effectiveness of screening for CRC and significant, benign lesions using flex-sig only compared to flex-sig in combination with faecal tests To evaluate to which extent (and in which direction) the study may influence overall endoscopic activity in the general population in the screening areas and in areas where controlled screening is not established Determine the prevalence of known types familial CRC in a general population and try to define other groups with intermediate increased risk Clarify possible psychosocial effects of endoscopic screening and how it may influence lifestyle and lifestyle related morbidity and overall mortality Population: 21,000 men and women, aged 50-64 years, living in the city of Oslo or the county of Telemark are drawn by randomisation (approx. 1:5) from the population registry and invited to have a flexible sigmoidoscopy examination. The control group constitutes 79,000 individuals. Those invited for flexible sigmoidoscopy are further randomised (1:1) to bring or not to bring 3 successive stool samples for FOBT on attendance for FS. Method: This is a once-only screening concept with bowel cleansing being limited to a 240 ml Sorbitol enema given on attendance. The threshold for work-up colonoscopy is low as a positive screening test is defined as any polyp >9mm, any histologically verified adenoma irrespective of size and a positive FOBT. The screening phase is limited to the period January 1999- January 2002 and the first follow-up results will not be reported until all entries have passed the 5-year mark (i.e. in early 2007).

Official Title
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Norwegian Colorectal Cancer Prevention Trial

Conditions
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Colorectal Cancer, Adenoma

Intervention / Treatment
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* Procedure: A 1 Intervention arm Flex Sig
* Procedure: A 2 Intervention arm Flex Sig + iFOBT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women Living in Oslo or Telemark Age 50-64 years Exclusion Criteria: Patients with previous open colorectal surgery (resections, enterostomies) Individuals in need of long lasting attention and nursing services (somatic or psychosocial reasons, mental retardation) On-going cytotoxic treatment or radiotherapy for malignant disease Severe chronic cardiac or lung disease (NYHA III-IV) Patients with heart valve replacement on life long anticoagulant therapy A coronary event during the last 3 months if having lead to hospitalisation Cerebrovascular accident during the last 3 months Resident abroad

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A 1 Intervention arm Flex Sig<br>Randomised from the population registry, age 50-64 years and invited for Flexible Sigmoidoscopy (Flex Sig) screening. Half of invitees are additionally invited to provide a stool sample for fecal occult blood testing (Intervention arm A 2). They are drawn directly from the population registry without prior consent to be randomized - approved by Regional Ethics Committees of South-East Norway.. | Procedure: A 1 Intervention arm Flex Sig<br>* Screening by flexible sigmoidoscopy<br>|
| No Intervention: B Control arm<br>No screening group randomised from population age 50-64 years. As for the active intervention arm, the control group was not informed about being randomized to 'no screening' since 'no screening' was the current usual care (and still is in 2015) in Norway - approved by Regional Ethics Committees of South-East Norway. | |
| Active Comparator: A 2 Intervention arm Flex Sig + iFOBT<br>Randomised from the population registry, age 50-64 years and invited for Flexible Sigmoidoscopy (Flex Sig) screening plus an immunochemical test for fecal occult blood (iFOBT). As for arms A 1 and B, they are drawn directly from the population registry without prior consent to be randomized. | Procedure: A 2 Intervention arm Flex Sig + iFOBT<br>* In addition to Flexible Sigmoidoscopy, half of arm A (randomised 1:1) is invited to provide stool samples for FOBT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions (polypectomy of adenomatous polyps).First evaluation after 5 years. | CRC incidence and mortality is followed | Evaluations in 2007 (published),2012,2017 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Determine the prevalence of known types familial CRC in a general population and try to define other groups with intermediate increased risk. Results in press 2005. | Determine the prevalence of familial CRC in a general population sample | Evaluated in 2005 (published) | 
| 2. Clarify possible psychosocial effects of endoscopic screening and how it may influence lifestyle and lifestyle related morbidity and overall mortality. Evaluation in 2005. | Determine psychosocial effects of invitation to screening and of screening findings | Evaluated in 2005 (published) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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screening, flexible sigmoidoscopy, fecal occult blood, cancer, colon, rectum