Clinical trial NCT00468910: Aspirin in Preventing Colorectal Cancer in Patients at Increased Risk of Colorectal Cancer
Official title: Spectral Markers in Aspirin Chemoprevention of Colonic Neoplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colon Cancer
Precancerous Condition
Rectal Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-05-03
Enrollment: 79
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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 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

Primary outcomes:
measure: Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months.
timeFrame: 3 months from baseline colonoscopy to end of intervention.
measure: Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months.
timeFrame: 3 months from baseline colonoscopy to end of intervention.
Secondary outcomes:
measure: Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3
timeFrame: 3 months from baseline colonoscopy to end of intervention.
measure: Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67
timeFrame: 3 months from baseline colonoscopy to end of intervention.
measure: Rectal Prostaglandin Levels as Measured by ELISA
timeFrame: 3 months from baseline colonoscopy to end of intervention.
Other outcomes:
measure: Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay
timeFrame: 3 months from baseline colonoscopy to end of intervention.
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Hemant Roy
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roy HK, Turzhitsky V, Wali R, Radosevich AJ, Jovanovic B, Della'Zanna G, Umar A, Rubin DT, Goldberg MJ, Bianchi L, De La Cruz M, Bogojevic A, Helenowski IB, Rodriguez L, Chatterton R, Skripkauskas S, Page K, Weber CR, Huang X, Richmond E, Bergan RC, Backman V. Spectral biomarkers for chemoprevention of colonic neoplasia: a placebo-controlled double-blinded trial with aspirin. Gut. 2017 Feb;66(2):285-292. doi: 10.1136/gutjnl-2015-309996. Epub 2015 Oct 26.