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

Rectal Cancer Clinical Trial

Official title:

Spectral Markers in Aspirin Chemoprevention of Colonic Neoplasia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00468910
• Other study ID #: NCI-2009-00841
• Secondary ID: NCI-2009-00841CD
• Status: Active, not recruiting
• Phase: Phase 2
• First received: May 2, 2007
• Last updated: December 6, 2013
• Start date: March 2007

Study information

• Verified date: December 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 115
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Colon Cancer
• Precancerous Condition
• Precancerous Conditions
• Rectal Cancer

Intervention

Drug:
• acetylsalicylic acid
Given orally
• placebo
Given orally

Other:
• laboratory biomarker analysis
Correlative study

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in spectral slope	The difference in the observed change from baseline in each arm, aspirin and placebo, will be compared.	From baseline to 3 months after completion of study treatment	No
Primary	Change in fractal dimension	The difference in the observed change from baseline in each arm, aspirin and placebo, will be compared.	From baseline to 3 months after completion of study treatment	No
Secondary	Colonic epithelial apoptosis as measured by immunohistochemical detection of cleaved caspase 3		Up to 3 months after completion of study treatment	No
Secondary	Colonic cell proliferation as measured by immunohistochemical detection of Ki67		Up to 3 months after completion of study treatment	No
Secondary	Rectal prostaglandin levels as measured by ELISA		Up to 3 months after completion of study treatment	No
Secondary	Platelet cyclooxygenase (COX) activity as measured by a peroxidase-based COX enzyme activity assay		Up to 3 months after completion of study treatment	No