Chemoprevention of Colorectal Adenomas

Study Overview
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Brief Summary
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The purpose of the study is to investigate if long-term treatment with three known drugs (acetylsalicylic acid, 1α 25-dihydroxy cholecalciferol, and calcium carbonate) prevents recurrence of colorectal adenomas.

Detailed Description
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This is a multicenter, randomized, parallel group, prospective, double blind, placebo controlled clinical trial of chemoprevention in patients at increased risk of developing colorectal cancer (CRC). The Colotech combination treatment (acetylsalicylic acid, 1α 25-dihydroxy cholecalciferol, and calcium carbonate) will be compared to placebo with regards to safety and efficacy during 3 years of treatment. The randomized treatment period will be preceded by a 3-week single blind placebo run-in period, which will assess patient's compliance to treatment. In order to collect data on the durability of treatment effect, follow-up data from a surveillance colonoscopy will be collected two years after the 3-year colonoscopy.

Official Title
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A Clinical Trial Evaluating the Efficacy and Safety of a Combination Treatment Administered Over 3 Years in Patients at Risk of Experiencing Recurrence of Colorectal Adenomas

Conditions
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Adenomatous Polyps

Intervention / Treatment
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* Drug: 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol)
* Drug: 75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)
* Drug: placebo to 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol)
* Drug: placebo to 75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)
* Procedure: Colonoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 40-75 years of age, both sexes. Colonoscopy including the cecum at trial entry The removed adenoma(s) have be to tubular, tubulovillous or villous, and fulfill one of the three following criteria: one adenoma with diameter ≥ 1 cm ≥ 2 adenomas of any size an adenoma of any size and familial disposition for colorectal cancer, as long as the person is a first degree relative with a colorectal cancer patient Exclusion Criteria: Familial Adenomatous Polyposis Syndrome Member of a family with hereditary non-polyposis colorectal cancer (HNPCC) Proctocolectomy (colonic and/or rectum resection permitted). Inflammatory bowel disease (Crohn´s disease, Ulcerative Colitis). Ischemic cardiovascular disease. Patients with known gastro-duodenal ulcer at time of inclusion. Cancer within the past 5 years

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment (calcitriol+ASA+CaCO3)<br>Daily dose of 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol, Rocaltrol; Roche, Basel, Switzerland), 75 mg acetylsalicylic acid (ASA), and 1250 mg calcium carbonate (CaCO3). The daily dose was administered as 1 capsule containing 0.5 mg calcitriol (Rocaltrol; Roche) and 2 tablets containing a 37.5-mg ASA core with a 625-mg calcium carbonate shell (tablet-in-tablet) that was made expressly for this study. Patients should take 1 capsule and 2 tablets daily, together or separately. Timing of the intake is not important; study medication can be taken with or without food. The daily dose should not be exceeded. Before randomization, patients were given the placebo and followed up for a 3-week run-in period. Only patients who showed a placebo medication compliance rate of at least 80% were eligible for randomization. The primary outcome was the proportion of patients with recurrence of any adenomas as detected by colonoscopy after 3 years of treatment. | Drug: 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol)<br> <br> Drug: 75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)<br> <br> Procedure: Colonoscopy<br> <br> |
| Placebo Comparator: Placebo to calcitriol+ASA+CaCO3<br>Daily dose of matching placebo to 0.5 mg calcitriol, 75 mg acetylsalicylic acid (ASA), and 1250 mg calcium carbonate (CaCO3). Patients should take 1 capsule and 2 tablets of placebo daily, together or separately. Timing of the intake is not important; study medication can be taken with or without food. The daily dose should not be exceeded. Before randomization, patients were given the placebo and followed up for a 3-week run-in period. Only patients who showed a placebo medication compliance rate of at least 80% were eligible for randomization. The primary outcome was the proportion of patients with recurrence of any adenomas as detected by colonoscopy after 3 years of treatment. | Drug: placebo to 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol)<br> <br> Drug: placebo to 75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)<br> <br> Procedure: Colonoscopy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of cumulative frequency of recurrence of colorectal adenomas post ablation | The purpose of the study is to investigate if long-term treatment with three known drugs (acetylsalicylic acid, 1α 25-dihydroxy cholecalciferol, and calcium carbonate) prevents recurrence of colorectal adenomas which were removed during colonoscopy. | 156 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of number and size of colorectal adenomas measured after three years of chemoprevention using the study drug | The purpose of the study is to investigate if long-term treatment with three known drugs (acetylsalicylic acid, 1α 25-dihydroxy cholecalciferol, and calcium carbonate) prevents recurrence of colorectal adenomas which were removed during colonoscopy. | 3 years | 
| Assessment of durability of polyp-free colon post surgical ablation for two years post-treatment with chemoprevention with study drug | The purpose of the study is to investigate if long-term treatment with three known drugs (acetylsalicylic acid, 1α 25-dihydroxy cholecalciferol, and calcium carbonate) prevents recurrence of colorectal adenomas which were removed during colonoscopy. | additional 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal, adenomas, prevention