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CompletedNCT00468910Updated May 31, 2017Results posted

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

A Phase 2 interventional study of acetylsalicylic acid and placebo in Colon Cancer, Precancerous Condition and Rectal Cancer, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged Up to 75 Years. Per ClinicalTrials.gov, last updated 2017-05-31.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
79
Allocation
Randomized
Ages
Up to 75 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Colon Cancer
  • Precancerous Condition
  • Rectal Cancer
03

In context

Precancerous Conditions

254 studies on the registry are indexed under Precancerous Conditions; 28 are open to participants now.

This study's enrollment of 79 is above the median of 60 across 163 interventional studies indexed under Precancerous Conditions.

Browse Precancerous Conditions studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
79 participants (actual)

Study arms

  • Experimental
    Arm I

    Patients receive oral acetylsalicylic acid (aspirin) once daily.

    Drug: acetylsalicylic acid · Other: laboratory biomarker analysis

  • Placebo comparator
    Arm II

    Patients receive oral placebo once daily.

    Drug: placebo · Other: laboratory biomarker analysis

Interventions

  • Drugacetylsalicylic acid

    Given orally

    Also known as: ASA, Ecotrin, Empirin, Extren

  • Drugplacebo

    Given orally

    Also known as: PLCB

  • Otherlaboratory biomarker analysis

    Correlative study

06

What researchers measure

Primary outcomes

  1. Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months.

    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.

    Time frame: 3 months from baseline colonoscopy to end of intervention.

  2. Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months.

    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

    Time frame: 3 months from baseline colonoscopy to end of intervention.

Secondary outcomes

  1. Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3

    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.

    Time frame: 3 months from baseline colonoscopy to end of intervention.

  2. Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67

    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.

    Time frame: 3 months from baseline colonoscopy to end of intervention.

  3. Rectal Prostaglandin Levels as Measured by ELISA

    Evaluate the effect of aspirin on rectal prostaglandin levels.

    Time frame: 3 months from baseline colonoscopy to end of intervention.

Other outcomes

  1. Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay

    Evaluate the effect of aspirin on platelet COX activity as measured by a peroxidase-based Cox enzyme activity assay.

    Time frame: 3 months from baseline colonoscopy to end of intervention.

07

Results

Posted May 31, 2017

Participant flow

The study opened to accrual 02/22/2007 and closed to accrual 08/10/2009. Subjects were recruited at Northwestern University and University of Chicago.

Participant flow — Overall Study
MilestoneAcetylsalicylic AcidPlacebo
Started4039
Randomization4039
Treatment3636
Post-treatment biopsy3636
Follow-up3636
Completed3636
Not completed43
Withdrew: Lost to follow-up21
Withdrew: Withdrawal by subject21
Withdrew: Medical contraindication01

Outcome measures

PrimaryChange of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months.

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.

Time frame:
3 months from baseline colonoscopy to end of intervention.
Reported as:
Mean · micron^-1
Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months.
micron^-1Acetylsalicylic AcidPlacebo
Baseline40.72 ± 16.9137.54 ± 21.64
Post Intervention43.45 ± 26.8437.52 ± 28.15
Statistical analysis
  • Acetylsalicylic Acid vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.11
PrimaryChange of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months.

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

Time frame:
3 months from baseline colonoscopy to end of intervention.
Reported as:
Mean · unitless
Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months.
unitlessAcetylsalicylic AcidPlacebo
Baseline142.41 ± 2570.8623.28 ± 2699.82
Post Intervention-407.78 ± 3470.69650.97 ± 3201.77
Statistical analysis
  • Acetylsalicylic Acid vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.17
SecondaryColonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3

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.

Time frame:
3 months from baseline colonoscopy to end of intervention.
Reported as:
Mean · Percentage of Total Cells
Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3
Percentage of Total CellsAcetylsalicylic AcidPlacebo
Baseline4.56 ± 4.275.24 ± 3.69
At 3 Months4.26 ± 4.447.26 ± 6.77
SecondaryChanges in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67

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.

Time frame:
3 months from baseline colonoscopy to end of intervention.
Reported as:
Mean · Percentage of Total Cells
Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67
Percentage of Total CellsAcetylsalicylic AcidPlacebo
Baseline38.07 ± 16.8340.45 ± 12.26
3 Months Intervention43.60 ± 14.7737.74 ± 13.37
SecondaryRectal Prostaglandin Levels as Measured by ELISA

Evaluate the effect of aspirin on rectal prostaglandin levels.

Time frame:
3 months from baseline colonoscopy to end of intervention.
Reported as:
Mean · pg/ml
Rectal Prostaglandin Levels as Measured by ELISA
pg/mlAcetylsalicylic AcidPlacebo
Baseline305.93 ± 300.01654.64 ± 1536.52
Post Intervention211.97 ± 134.32209.02 ± 134.33
Other pre-specifiedPlatelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay

Evaluate the effect of aspirin on platelet COX activity as measured by a peroxidase-based Cox enzyme activity assay.

Time frame:
3 months from baseline colonoscopy to end of intervention.
Reported as:
Mean · pg/ml
Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay
pg/mlAcetylsalicylic AcidPlacebo
Baseline712976.73 ± 2082413.36430109.56 ± 798782.31
Post Intervention6914.87 ± 20891.41200233.5 ± 463029.1

Adverse events

Collected over 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Acetylsalicylic Acid—0/40 (0%)17/40 (42.5%)
Placebo—0/39 (0%)21/39 (53.8%)
Most frequent other events
Showing 10 of 30
Most frequent other events
EventAcetylsalicylic AcidPlacebo
Pain: Head/HeadacheGeneral disorders1/404/39
Pain: StomachGeneral disorders2/402/39
Upper Airway NosInfections and infestations1/402/39
Infection - OtherInfections and infestations0/402/39
DizzinessNervous system disorders0/402/39
Pain: Abdomen NosGeneral disorders2/401/39
Blood/Bone Marrow: HemoglobinBlood and lymphatic system disorders1/401/39
Blood/Bone Marrow: OtherBlood and lymphatic system disorders1/401/39
Hemorrhage with SurgeryBlood and lymphatic system disorders0/401/39
HeartburnGastrointestinal disorders0/401/39

Baseline characteristics

72 of the 79 subjects who were randomized completed the primary endpoint (3-month tissue biopsy); 36 from each arm.

Age, Categorical
Age, Categorical(Participants)Acetylsalicylic AcidPlaceboTotal
<=18 years000
Between 18 and 65 years333467
>=65 years7512
Sex: Female, Male
Sex: Female, Male(Participants)Acetylsalicylic AcidPlaceboTotal
Female151631
Male252348
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Acetylsalicylic AcidPlaceboTotal
Hispanic or Latino303
Not Hispanic or Latino373976
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Acetylsalicylic AcidPlaceboTotal
American Indian or Alaska Native000
Asian022
Native Hawaiian or Other Pacific Islander000
Black or African American213
White373673
More than one race101
Unknown or Not Reported000
08

Study locations

1 site
  • Northwestern University
    Chicago, Illinois 60611, United States
09

References and documents

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. PubMed 26503631 ↗

Individual participant data

Plan to share: Yes

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 31, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00468910
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
May 3, 2007
Start date
Mar 2007
Primary completion
Dec 2009
Completion
Aug 2011
Results posted
May 31, 2017
Last update
May 31, 2017

Study contacts

Hemant Roy
principal investigator · Northwestern University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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