Chemoprevention of Colorectal Adenomas

Phase 3

Terminated

Conditions: Adenomatous Polyps

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

Registration Number: NCT00486512

Lead Sponsor: Colotech A/S

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 350

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:
1. one adenoma with diameter ≥ 1 cm
2. ≥ 2 adenomas of any size
3. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Treatment (calcitriol+ASA+CaCO3)	Colonoscopy	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.
Placebo to calcitriol+ASA+CaCO3	placebo to 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol)	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.
Placebo to calcitriol+ASA+CaCO3	placebo to 75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)	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.
Active Treatment (calcitriol+ASA+CaCO3)	0.5 mg calcitriol (1a -25-dihydroxycholecalciferol)	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.
Active Treatment (calcitriol+ASA+CaCO3)	75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)	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.
Placebo to calcitriol+ASA+CaCO3	Colonoscopy	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.

Primary Outcome Measures

Name	Time	Method
Assessment of cumulative frequency of recurrence of colorectal adenomas post ablation	156 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Assessment of number and size of colorectal adenomas measured after three years of chemoprevention using the study drug	3 years	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.
Assessment of durability of polyp-free colon post surgical ablation for two years post-treatment with chemoprevention with study drug	additional 2 years	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.

Trial Locations

Locations (39): Alabama Digestive Disorders Center, P.C.
🇺🇸
Huntsville, Alabama, United States
San Diego Digestive Disease Consultants, Inc.
🇺🇸
San Diego, California, United States
Advance Digestive Care
🇺🇸
Clearwater, Florida, United States
Internal Medicine Specialists
🇺🇸
Orlando, Florida, United States
Atlanta Center for Gastroenterology, PC
🇺🇸
Decatur, Georgia, United States
Central Indiana Gastroenterology Group
🇺🇸
Anderson, Indiana, United States
Gastrointestinal Clinic of Quad Cities
🇺🇸
Davenport, Iowa, United States
University of Kentucky Medical Center
🇺🇸
Lexington, Kentucky, United States
Gastroenterology Associates of Eastern Maine
🇺🇸
Bangor, Maine, United States
Digestive Disorders Associates
🇺🇸
Annapolis, Maryland, United States
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Alabama Digestive Disorders Center, P.C.
🇺🇸Huntsville, Alabama, United States