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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
GroupInterventionDescription
Active Treatment (calcitriol+ASA+CaCO3)ColonoscopyDaily 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+CaCO3placebo 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+CaCO3placebo 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+CaCO3ColonoscopyDaily 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
NameTimeMethod
Assessment of cumulative frequency of recurrence of colorectal adenomas post ablation156 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
NameTimeMethod
Assessment of number and size of colorectal adenomas measured after three years of chemoprevention using the study drug3 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 drugadditional 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)

Central Indiana Gastroenterology Group

🇺🇸

Anderson, Indiana, United States

Atlanta Center for Gastroenterology, PC

🇺🇸

Decatur, Georgia, United States

Gastroenterology Associates of Eastern Maine

🇺🇸

Bangor, Maine, United States

Stony Brook University Medical Center

🇺🇸

Stony Brook, New York, United States

Out-patient clinic No. 3 of the Administration for the President of Russian Federation

🇷🇺

Moscow, Russian Federation

St. Petersburg Central Medical Sanitary Department of Federal Biological Agency

🇷🇺

St. Petersburg, Russian Federation

San Diego Digestive Disease Consultants, Inc.

🇺🇸

San Diego, California, United States

Northwest Gastroenterology Clinic

🇺🇸

Portland, Oregon, United States

Wisconsin Center for Advanced Research

🇺🇸

Milwaukee, Wisconsin, United States

Russian Center of Functional Surgical Gastroenterology

🇷🇺

Krasnodar, Russian Federation

Dept of Gastroenterology and Nutrition

🇷🇺

Saint Petersburg, Russian Federation

Alabama Digestive Disorders Center, P.C.

🇺🇸

Huntsville, Alabama, United States

Digestive Disorders Associates

🇺🇸

Annapolis, Maryland, United States

Gastrointestinal Clinic of Quad Cities

🇺🇸

Davenport, Iowa, United States

Office of Alan A. Rosen, M.D.

🇺🇸

Baltimore, Maryland, United States

University of Kentucky Medical Center

🇺🇸

Lexington, Kentucky, United States

Colon and Rectal Surgery Associates, Ltd.

🇺🇸

Saint Paul, Minnesota, United States

Digestive Health Specialists, PA

🇺🇸

Tupelo, Mississippi, United States

Wilmington Gastroenterology Associates

🇺🇸

Wilmington, North Carolina, United States

Regional Gastroenterology Associates of Lancaster, Ltd

🇺🇸

Lancaster, Pennsylvania, United States

Advanced Healthcare, S.C.

🇺🇸

Milwaukee, Wisconsin, United States

North Texas Gastroenterology Consultants

🇺🇸

Dallas, Texas, United States

Saint-Petersburg State City Hospital No 26

🇷🇺

Saint-Petersburg, Russian Federation

State Medical Stomatological University

🇷🇺

Moscow, Russian Federation

2nd Terapy Department Military Medical Academy

🇷🇺

St. Petersburg, Russian Federation

Yaroslav City Clinical Hospital No 2

🇷🇺

Yaroslavl, Russian Federation

Smolensk City Clinical Hospital No 1

🇷🇺

Smolensk, Russian Federation

Out-patient clinic No. 2 of the Administration for the President of Russian Federation

🇷🇺

Moscow, Russian Federation

Rostov State Medical University

🇷🇺

Rostov-on-Don, Russian Federation

All Russian Center of Emergency and Radiation Medicine of EMERCOM of Russia

🇷🇺

St. Petersburg, Russian Federation

Stavropol State Medical Academy

🇷🇺

Stavropol, Russian Federation

Advance Digestive Care

🇺🇸

Clearwater, Florida, United States

Alamo Medical Research

🇺🇸

San Antonio, Texas, United States

Internal Medicine Specialists

🇺🇸

Orlando, Florida, United States

Digestive Health Specialists PA

🇺🇸

Winston-Salem, North Carolina, United States

Gastroenterology Research Associates

🇺🇸

Cedar Knolls, New Jersey, United States

Leningrad Regional Clinical Hospital

🇷🇺

Saint-Petersburg, Russian Federation

Federal State Enterprise "Russian Federation Defense Ministry Burdenko Main Military Clinical Hospital"

🇷🇺

Moscow, Russian Federation

Borgess Medical Center

🇺🇸

Kalamazoo, Michigan, United States

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