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Phase II Study Of Colorectal ACF Screening, Regression And Prevention In High Risk Participants

Phase 2
40 Years
80 Years
Not Enrolling
Colorectal Cancer

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Trial Information

Phase II Study Of Colorectal ACF Screening, Regression And Prevention In High Risk Participants


- Determine the percentage change in colorectal aberrant crypt foci (ACF) in patients
with a history of colorectal cancer or at high risk for colorectal cancer when treated
with sulindac vs aspirin vs ursodiol.

- Determine the safety and efficacy of these drugs, in terms of ability to cause
regression of existing colorectal ACF and prevent new ACF development, in these

OUTLINE: This is a partially blinded, randomized, placebo-controlled study. Patients are
stratified according to colorectal neoplasia (adenoma vs carcinoma). Patients are randomized
to 1 of 4 treatment arms.

- Arm I: Patients receive oral sulindac twice daily.

- Arm II: Patients receive oral aspirin once daily.

- Arm III: Patients receive oral ursodiol three times daily.

- Arm IV: Patients receive oral sulindac placebo twice daily. In all arms, treatment
continues for 12 months in the absence of disease progression or unacceptable toxicity.

Patients undergo a colonoscopy at baseline and at the end of treatment.

Patients are followed at 2 months after the end of treatment.

PROJECTED ACCRUAL: A total of 172 patients (43 per treatment arm) with a history of
colorectal cancer or adenomas will be accrued for this study. A total of 20 additional
patients with no elevated risk of colorectal neoplasia will be accrued, but not randomized,
for this study.

Inclusion Criteria:

1. Male or female subjects, age 40-80 years

2. with >5 colorectal ACF and a prior history of colorectal cancer defined as Dukes A/B1
carcinoma within 5 years of entry or any stage of colorectal cancer if at least 5
years post surgical resection (86 subjects)

3. with >5 colorectal ACF and recent/current history of colorectal adenoma(s) defined as
one of the following: one adenomatous polyp >1cm or two or more adenomatous polyps of
any size or one adenomatous polyp of any size and a documented history of adenomatous
polyp(s) (86 subjects)

4. No elevated risk of colorectal cancer or adenomas (20 subjects)

5. Subjects will be permitted to use Nasonex but all other nasal steroids are
prohibited. Subjects may change to Nasonex but must have discontinued previous nasal
steroid use for at least 30 days prior to study randomization.

6. If participant is female and of childbearing potential, she must agree to use
adequate contraception and must have a negative serum pregnancy test within 14 days
prior to study drug administration

7. No use of investigational agent(s) within the last 3 months or at the discretion of
the medical monitor

8. The subject will be allowed to proceed to randomization so long as all of the
following laboratory criteria are met on baseline evaluation: Hgb > 10.0 g/dl,
platelet count > 100,000/ul; WBC > 3,000/ul; ALT < 2 x upper limit of normal; AST < 2
x upper limit of normal, and total bilirubin <1.5mg/100ml.

9. Patients requiring use of hormone modulators such as Tamoxifen or Arimidex will be
permitted to enroll providing they meet all of the eligibility criteria noted above

Exclusion Criteria:

1. Known diagnosis of FAP, hereditary non-polyposis colon cancer (HNPCC), or
inflammatory bowel disease

2. History of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs , salicylates,
or ursodeoxycholic acid

3. Use of NSAIDs, including aspirin, at any dose during the six months prior to study
entry will require a three month washout period prior to eligibility beginning with
the time of the last dose. Participants must be off all NSAIDs for three months prior
to study entry. Individuals on cardioprotectant aspirin at any dose will not be

4. History of gastroduodenal ulcers documented endoscopically would preclude a patient
from participation in the trial

5. Known inability to participate in the scheduled follow-up tests.

6. Significant medical or psychiatric problems which would make the patient a poor
protocol candidate, in the opinion of the principal investigator.

7. "Unacceptable clinical risk" to proceed (based upon the subclinical discoveries made
via baseline colonoscopy and biopsies).

8. Patient has undergone a total colectomy

9. Patient has received chemotherapy within the past 6 months of randomization into
study. Topical chemotherapy will be assessed on a case-by-case basis. Any history of
pelvic or rectal radiation therapy will exclude a patient from participating.

10. History of invasive carcinoma in the past five years (except patients with Dukes A/B1
carcinoma within 5 years of entry or any stage of colorectal cancer if at least 5
years post surgical resection)

11. Patients with rectal cancer are excluded except for transanal excision without

12. Patients with acute liver disease, unexplained transaminase elevations or a history
of renal stones would be excluded.

13. Participants will not be permitted to be randomized into the trial if any of the
following laboratory values are reported at baseline : Hgb < 10.0 g/dl, platelet
count <100,000/ul; WBC < 3,000/ul; ALT > 2 x upper limit of normal; AST > 2 x upper
limit of normal, and total bilirubin >1.5mg/100ml.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Outcome Measure:

Percentage Change in Colorectal ACF Patients Treated with Sulindac, Aspirin or Ursodiol

Outcome Time Frame:

12 Months

Safety Issue:


Principal Investigator

Robert S. Bresalier, MD

Investigator Role:

Study Chair

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2003

Completion Date:

May 2006

Related Keywords:

  • Colorectal Cancer
  • colorectal cancer
  • stage I colon cancer
  • stage II colon cancer
  • stage III colon cancer
  • stage IV colon cancer
  • Colorectal Neoplasms



M.D. Anderson Cancer Center at University of Texas Houston, Texas  77030