Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Prevention Closed 30 to 80 UUMC-9102 NCI-P92-0018

Objectives

I.  Determine whether sulindac causes regression of sporadically occurring 
colorectal adenomas.

II.  Determine whether sulindac causes consistent changes in intermediate 
markers for colorectal cancer, including colonic mucosal prostaglandin E2 and 
whole crypt mitotic count, flow cytometry, and proliferating cell nuclear 
antigen labeling indices.

III.  Determine whether changes in these intermediate markers correlate with 
adenoma regression.

IV.  Determine the optimal dosage of sulindac for chemoprevention of 
colorectal adenomas to be used in a Phase III study of cancer chemoprevention.

V.  Measure the type and incidence of side effects occurring during long-term 
sulindac treatment.

VI.  Develop plans for a multicenter Phase III study of sulindac for 
chemoprevention of colorectal cancer.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  Not specified

Endocrine therapy:
  No concurrent corticosteroids

Radiotherapy:
  Not specified

Surgery:
  No history of resection of more than 40 cm of colon or of the
  ileocecal valve

Other:
  No concurrent salicylates, NSAIDs, anticoagulants, or
  antiplatelet agents
     Aspirin (not to exceed 325 mg/day) allowed

Patient Characteristics:

Age:
  30 to 80

Performance status:
  SWOG 0 or 1 (Karnofsky 70-100%)

Life expectancy:
  No serious underlying medical or psychiatric illness that
  would limit expected survival

Hematopoietic:
  WBC at least 4,000
  Platelets at least 130,000
  Hb at least 13 g/dl

Hepatic:
  Bilirubin no greater than 2.0 mg/dl
  AST no greater than 2 x normal
  PT/PTT within normal limits

Renal:
  Creatinine no greater than 1.5 mg/dl
  Proteinuria less than 1+ by dipstick
  No more than 5 WBC or RBC/HPF

Other:
  No history of allergy or anaphylactic reaction to sulindac,
     aspirin, or other NSAIDs
  No contraindication to colonoscopy
  No history of peptic ulcer or inflammatory bowel disease
     within 12 months
  No other serious underlying medical or psychiatric illness
     that would preclude study completion or informed consent
  Negative pregnancy test required of fertile women

General Eligibility Criteria:

--Subject Characteristics--

Persons referred for colonoscopy or sigmoidoscopy to the
Gastroenterology Divisions of participating institutions who
are found to have left-sided polyps 4-12 mm in diameter

--Prior/Concurrent Therapy--

Biologic therapy:
  Not specified

Chemotherapy:
  Not specified

Endocrine therapy:
  No concurrent corticosteroids

Radiotherapy:
  Not specified

Surgery:
  No history of resection of more than 40 cm of colon or of the
  ileocecal valve

Other:
  No concurrent salicylates, NSAIDs, anticoagulants, or
  antiplatelet agents
     Aspirin (not to exceed 325 mg/day) allowed

--Patient Characteristics--

Age:
  30 to 80

Performance status:
  SWOG 0 or 1 (Karnofsky 70-100%)

Life expectancy:
  No serious underlying medical or psychiatric illness that
  would limit expected survival

Hematopoietic:
  WBC at least 4,000
  Platelets at least 130,000
  Hb at least 13 g/dl

Hepatic:
  Bilirubin no greater than 2.0 mg/dl
  AST no greater than 2 x normal
  PT/PTT within normal limits

Renal:
  Creatinine no greater than 1.5 mg/dl
  Proteinuria less than 1+ by dipstick
  No more than 5 WBC or RBC/HPF

Other:
  No history of allergy or anaphylactic reaction to sulindac,
     aspirin, or other NSAIDs
  No contraindication to colonoscopy
  No history of peptic ulcer or inflammatory bowel disease
     within 12 months
  No other serious underlying medical or psychiatric illness
     that would preclude study completion or informed consent
  Negative pregnancy test required of fertile women

Expected Enrollment

60 patients (20 per arm) will be accrued over a period of 27 months.

Outline

Randomized, double-blind study.  All patients are treated on Regimen A for 1 
month then randomized to Arm I, II, or III.

Regimen A:  Compliance study.  Placebo, PLCB.

Arm I:  Chemoprevention.  Sulindac.

Arm II:  Chemoprevention plus Placebo.  Sulindac plus PLCB.

Arm III:  Control.  PLCB.

Trial Contact Information

Trial Lead Organizations

Huntsman Cancer Institute at University of Utah

James DiSario, MD, Protocol chair		Ph: 801-581-5036; 877-585-0303 Email: james.disario@hsc.utah.edu