Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00468910
Recruitment Status : Completed
First Posted : May 3, 2007
Results First Posted : May 31, 2017
Last Update Posted : May 31, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE May 2, 2007
First Posted Date  ICMJE May 3, 2007
Results First Submitted Date  ICMJE December 15, 2015
Results First Posted Date  ICMJE May 31, 2017
Last Update Posted Date May 31, 2017
Study Start Date  ICMJE March 2007
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2017)
  • Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months. [ Time Frame: 3 months from baseline colonoscopy to end of intervention. ]
    Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. SPEC characterizes the size distribution of macromolecular complexes and other intracellular structures, with a decrease of the spectral slope implying a shift of the size distribution of intracellular structures toward smaller sizes. Spectral markers SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture.
  • Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months. [ Time Frame: 3 months from baseline colonoscopy to end of intervention. ]
    Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. FRAC characterizes the spatial autocorrelation function of mass density distribution in tissue. SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2007)
  • Observed change from baseline in spectral slope and fractal dimension
  • Reversal of neoplastic micro-architectural changes as assessed by 4D-ELF parameters by aspirin
Change History Complete list of historical versions of study NCT00468910 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2017)
  • Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3 [ Time Frame: 3 months from baseline colonoscopy to end of intervention. ]
    Evaluate the effect of aspirin on colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of cleaved caspase 3 .These were performed on samples that had been previously analyzed for 4D-ELF.
  • Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67 [ Time Frame: 3 months from baseline colonoscopy to end of intervention. ]
    Evaluate the effect of aspirin on colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of Ki-67. These were performed on samples that had been previously analyzed for 4D-ELF.
  • Rectal Prostaglandin Levels as Measured by ELISA [ Time Frame: 3 months from baseline colonoscopy to end of intervention. ]
    Evaluate the effect of aspirin on rectal prostaglandin levels.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2007)
  • Colonic epithelial apoptosis and cell proliferation as measured by immunohistochemical detection of cleaved caspase 3 and Ki-67 expression
  • Rectal Prostaglandin Levels as Measured by ELISA
  • Platelet cyclooxygenase (COX) activity as measured by a peroxidase-based COX enzyme activity assay
  • Correlation of spectral marker alterations with UGT1A6 genotype
  • Rectal prostaglandin levels
  • Rectal apoptosis
  • Rectal proliferation
Current Other Pre-specified Outcome Measures
 (submitted: April 26, 2017)
Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay [ Time Frame: 3 months from baseline colonoscopy to end of intervention. ]
Evaluate the effect of aspirin on platelet COX activity as measured by a peroxidase-based Cox enzyme activity assay.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Aspirin in Preventing Colorectal Cancer in Patients at Increased Risk of Colorectal Cancer
Official Title  ICMJE Spectral Markers in Aspirin Chemoprevention of Colonic Neoplasia
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Colon Cancer
  • Precancerous Condition
  • Rectal Cancer
Intervention  ICMJE
  • Drug: acetylsalicylic acid
    Given orally
    Other Names:
    • ASA
    • Ecotrin
    • Empirin
    • Extren
  • Drug: placebo
    Given orally
    Other Name: PLCB
  • Other: laboratory biomarker analysis
    Correlative study
Study Arms  ICMJE
  • Experimental: Arm I
    Patients receive oral acetylsalicylic acid (aspirin) once daily.
    Interventions:
    • Drug: acetylsalicylic acid
    • Other: laboratory biomarker analysis
  • Placebo Comparator: Arm II
    Patients receive oral placebo once daily.
    Interventions:
    • Drug: placebo
    • Other: laboratory biomarker analysis
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 26, 2017)
79
Original Enrollment  ICMJE
 (submitted: May 2, 2007)
80
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00468910
Other Study ID Numbers  ICMJE NCI-2009-00841
NCI-2009-00841 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000652929
NCI 04-2-03 ( Other Identifier: Northwestern University )
NWU04-2-03 ( Other Identifier: DCP )
N01CN35157 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Hemant Roy Northwestern University
PRS Account National Cancer Institute (NCI)
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP