Chemoprevention of Colorectal Adenomas

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

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.

Study Overview

• Status: Terminated
• Conditions: Adenomatous Polyps
• Intervention / Treatment: Procedure: Colonoscopy; 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)

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.

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Krasnodar, Russian Federation, 350086
    • Russian Center of Functional Surgical Gastroenterology
  • Moscow, Russian Federation, 105229
    • Federal State Enterprise "Russian Federation Defense Ministry Burdenko Main Military Clinical Hospital"
  • Moscow, Russian Federation, 119146
    • Out-patient clinic No. 2 of the Administration for the President of Russian Federation
  • Moscow, Russian Federation, 127473
    • State Medical Stomatological University
  • Moscow, Russian Federation, 129090
    • Out-patient clinic No. 3 of the Administration for the President of Russian Federation
  • Rostov-on-Don, Russian Federation, 344022
    • Rostov State Medical University
  • Saint Petersburg, Russian Federation, 197110
    • Dept of Gastroenterology and Nutrition
  • Saint-Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinical Hospital
  • Saint-Petersburg, Russian Federation, 196247
    • Saint-Petersburg State City Hospital No 26
  • Smolensk, Russian Federation, 214001
    • Smolensk City Clinical Hospital No 1
  • St. Petersburg, Russian Federation, 193163
    • 2nd Terapy Department Military Medical Academy
  • St. Petersburg, Russian Federation, 194044
    • All Russian Center of Emergency and Radiation Medicine of EMERCOM of Russia
  • St. Petersburg, Russian Federation, 194291
    • St. Petersburg Central Medical Sanitary Department of Federal Biological Agency
  • Stavropol, Russian Federation, 355017
    • Stavropol State Medical Academy
  • Yaroslavl, Russian Federation, 150010
    • Yaroslav City Clinical Hospital No 2
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
      • Alabama Digestive Disorders Center, P.C.
  • California
    • San Diego, California, United States, 92110
      • San Diego Digestive Disease Consultants, Inc.
  • Florida
    • Clearwater, Florida, United States, 33756
      • Advance Digestive Care
    • Orlando, Florida, United States, 32806
      • Internal Medicine Specialists
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta Center for Gastroenterology, PC
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Central Indiana Gastroenterology Group
  • Iowa
    • Davenport, Iowa, United States, 52807
      • Gastrointestinal Clinic of Quad Cities
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Gastroenterology Associates of Eastern Maine
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Digestive Disorders Associates
    • Baltimore, Maryland, United States, 21215
      • Office of Alan A. Rosen, M.D.
  • Michigan
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Colon and Rectal Surgery Associates, Ltd.
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Digestive Health Specialists, PA
  • New Jersey
    • Cedar Knolls, New Jersey, United States, 07927
      • Gastroenterology Research Associates
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Wilmington, North Carolina, United States, 28403
      • Wilmington Gastroenterology Associates
    • Winston-Salem, North Carolina, United States, 27103
      • Digestive Health Specialists PA
  • Oregon
    • Portland, Oregon, United States, 97210
      • Northwest Gastroenterology Clinic
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604-3200
      • Regional Gastroenterology Associates of Lancaster, Ltd
  • Texas
    • Dallas, Texas, United States, 75248
      • North Texas Gastroenterology Consultants
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research
    • Milwaukee, Wisconsin, United States, 53209
      • Advanced Healthcare, S.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Treatment (calcitriol+ASA+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.	Procedure: Colonoscopy; Drug: 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol); Drug: 75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)
Placebo Comparator: Placebo to calcitriol+ASA+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.	Procedure: Colonoscopy; Drug: placebo to 0.5 mg calcitriol (1a -25-dihydroxycholecalciferol); Drug: placebo to 75 mg acetylsalicylic acid (ASA) + 1250 mg calcium carbonate (CaCO3)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Colotech A/S
• Investigators: Study Director: Hans Raskov, M.D., Colotech A/S

Publications and helpful links

General Publications

• Pommergaard HC, Burcharth J, Rosenberg J, Raskov H. Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial. Gastroenterology. 2016 Jan;150(1):114-122.e4. doi: 10.1053/j.gastro.2015.09.010. Epub 2015 Sep 25.
• Carroll C, Cooper K, Papaioannou D, Hind D, Pilgrim H, Tappenden P. Supplemental calcium in the chemoprevention of colorectal cancer: a systematic review and meta-analysis. Clin Ther. 2010 May;32(5):789-803. doi: 10.1016/j.clinthera.2010.04.024.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: June 12, 2007
• First Submitted That Met QC Criteria: June 13, 2007
• First Posted (Estimate): June 14, 2007

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: colorectal, adenomas, prevention
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Adenoma; Adenomatous Polyps; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Gastrointestinal Agents; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Antacids; Calcium Channel Agonists; Aspirin; Calcium; Calcium, Dietary; Calcium Carbonate; Calcitriol; Dihydroxycholecalciferols
• Other Study ID Numbers: COLO CP-01-US