Aspirin in Preventing Colorectal Cancer in Patients at Increased Risk of Colorectal Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Precancerous Condition; Colon Cancer; Rectal Cancer

Treatments: Drug: acetylsalicylic acid; Drug: placebo; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: NIH

Identifiers

NCT00468910

NWU04-2-03 (Other Identifier)

NCI-2009-00841 (Registry Identifier)

N01CN35157 (U.S. NIH Grant/Contract)

NCI 04-2-03 (Other Identifier)

CDR0000652929

Details and patient eligibility

About

This randomized phase II trial is studying how well aspirin works in preventing colorectal cancer in patients at increased risk of colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of aspirin may prevent colorectal cancer.

Full description

PRIMARY OBJECTIVE:

I. Determine whether acetylsalicylic acid (aspirin) will alter spectral markers (i.e., spectral slope and fractal dimension) in distal colonic mucosa of patients who are at increased risk for the development or recurrence of colorectal cancer.

SECONDARY OBJECTIVES:

I. Assess the effect of this drug on colonic epithelial apoptosis and cell proliferation in these patients.

II. Assess the effect of this drug on rectal prostaglandin levels in these patients.

III. Assess the effect of this drug on platelet cyclooxygenase activity in these patients.

IV. Correlate changes in spectral markers with UGT1A6 genotype in patients treated with this drug.

OUTLINE: This is a multicenter, randomized, double-blind, placebo-controlled study. Patients are stratified by clinical site and adenoma/carcinoma maximal size. Patients with abnormal spectral biomarkers are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral acetylsalicylic acid (aspirin) once daily.

ARM II: Patients receive oral placebo once daily.

In both arms, treatment continues for 3 months in the absence of unacceptable toxicity.

Patients undergo flexible sigmoidoscopy and biopsies as well as blood collection at baseline (during prestudy colonoscopy) and at completion of study treatment for comparison of spectral signatures with biomarkers of both aspirin activity (including plasma cyclooxygenase activity and rectal prostaglandin levels) as well as with biomarkers associated with antineoplastic alteration (including apoptosis and cell proliferation). UGT1A6 genotyping analysis is also performed.

After completion of study treatment, patients are followed at 3 months.

Enrollment: 79 patients

Sex: All

Ages: Under 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Criteria:

• No active or metastatic cancer within the past 6 months

• Scheduled to undergo colonoscopy for colonic neoplasia surveillance

• Hemoglobin >= 12.0 g/dL

• Platelet count >= 120,000/mm^3

• AST or ALT =< 1.5 times upper limit of normal (ULN)

• Alkaline phosphatase =< 1.5 times ULN

• Bilirubin =< 1.5 times ULN

• BUN =< 40 mg/dL

• Glomerular filtration rate >= 45 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No coagulopathy

• No anemia

• No history of peptic ulcer disease or gastrointestinal hemorrhage

• No history of cerebrovascular accident

• No uncontrolled hypertension

• No history of intolerance or allergy to aspirin or to NSAIDs

• No liver disease as manifested by signs or symptoms of cirrhosis

• No endoscopic or radiographic evidence of portal hypertension

• No active colitis by endoscopy

• No history of inflammatory bowel disease

• No requirement for aspirin as medical therapy (i.e., post-myocardial infarction or transient ischemic attack)

• No untreated helicobacter pylori infection

• History of significant colonic neoplasia, defined as 1 of the following:

  • Adenoma within the past 6 years
  • Colorectal cancer within the past 6 years
  • Known adenoma on present exam
  • Histologically confirmed polyps seen on imaging

• INR =< 1.5

• At least 6 months since prior cancer treatment

• No other concurrent acetylsalicylic acid (aspirin)-containing products or non-steroidal anti-inflammatory drugs (NSAIDs)

• No concurrent systemic corticosteroids

• No other concurrent anticoagulants or antiplatelet agents

• No concurrent investigational drugs

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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79 participants in 2 patient groups, including a placebo group

Arm I

Experimental group

Description:

Patients receive oral acetylsalicylic acid (aspirin) once daily.

Treatment:

Other: laboratory biomarker analysis

Drug: acetylsalicylic acid

Arm II

Placebo Comparator group

Description:

Patients receive oral placebo once daily.

Treatment:

Other: laboratory biomarker analysis

Drug: placebo