Chemoprevention of Colorectal Adenomas

Colotech

Status and phase: Terminated; Phase 3

Conditions: Adenomatous Polyps

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00486512

COLO CP-01-US

Details and patient eligibility

About

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.

Full 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.

Enrollment: 350 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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350 participants in 2 patient groups, including a placebo group

Active Treatment (calcitriol+ASA+CaCO3)

Experimental group

Description:

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.

Treatment:

Drug: 75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)

Drug: 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol)

Procedure: Colonoscopy

Placebo to calcitriol+ASA+CaCO3

Placebo Comparator group

Description:

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.

Treatment:

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