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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00468910
First received: May 2, 2007
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Precancerous Condition
Rectal Cancer
Drug: acetylsalicylic acid
Drug: placebo
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Spectral Markers in Aspirin Chemoprevention of Colonic Neoplasia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Change in spectral slope [ Time Frame: From baseline to 3 months after completion of study treatment ] [ Designated as safety issue: No ]
    The difference in the observed change from baseline in each arm, aspirin and placebo, will be compared.

  • Change in fractal dimension [ Time Frame: From baseline to 3 months after completion of study treatment ] [ Designated as safety issue: No ]
    The difference in the observed change from baseline in each arm, aspirin and placebo, will be compared.


Secondary Outcome Measures:
  • Colonic epithelial apoptosis as measured by immunohistochemical detection of cleaved caspase 3 [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]
  • Colonic cell proliferation as measured by immunohistochemical detection of Ki67 [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]
  • Rectal prostaglandin levels as measured by ELISA [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]
  • Platelet cyclooxygenase (COX) activity as measured by a peroxidase-based COX enzyme activity assay [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 115
Study Start Date: March 2007
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral acetylsalicylic acid (aspirin) once daily.
Drug: acetylsalicylic acid
Given orally
Other Names:
  • ASA
  • Ecotrin
  • Empirin
  • Extren
Other: laboratory biomarker analysis
Correlative study
Placebo Comparator: Arm II
Patients receive oral placebo once daily.
Drug: placebo
Given orally
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative study

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468910

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Investigators
Principal Investigator: Hemant Roy Northwestern University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00468910     History of Changes
Other Study ID Numbers: NCI-2009-00841, NCI-2009-00841, CDR0000652929, NCI 04-2-03, NWU04-2-03, N01CN35157
Study First Received: May 2, 2007
Last Updated: December 6, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Precancerous Conditions
Neoplasms
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 19, 2014