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)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Colon Cancer
Precancerous Condition
Rectal Cancer
Interventions Drug: acetylsalicylic acid
Drug: placebo
Other: laboratory biomarker analysis
Enrollment 79
Recruitment Details 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.
Pre-assignment Details A total of 110 subjects met the clinical definition of high risk for colorectal cancer, were entered onto the trial, and underwent initial spectral analysis. Of these, 81 had a cancer-associated spectral signature in histologically normal colonic mucosa.79 of these 81 subjects were randomized and began the study intervention
Arm/Group Title Acetylsalicylic Acid Placebo
Hide Arm/Group Description Patients receive oral acetylsalicylic acid (aspirin) once daily. Patients receive oral placebo once daily.
Period Title: Overall Study
Started 40 39
Randomization 40 39
Treatment 36 36
Post-Treatment Biopsy 36 36
Follow-up 36 36
Completed 36 36
Not Completed 4 3
Reason Not Completed
Lost to Follow-up             2             1
Withdrawal by Subject             2             1
Medical Contraindication             0             1
Arm/Group Title Acetylsalicylic Acid Placebo Total
Hide Arm/Group Description Patients receive oral acetylsalicylic acid (aspirin) once daily. Patients receive oral placebo once daily. Total of all reporting groups
Overall Number of Baseline Participants 40 39 79
Hide Baseline Analysis Population Description
72 of the 79 subjects who were randomized completed the primary endpoint (3-month tissue biopsy); 36 from each arm.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 39 participants 79 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
33
  82.5%
34
  87.2%
67
  84.8%
>=65 years
7
  17.5%
5
  12.8%
12
  15.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 39 participants 79 participants
Female
15
  37.5%
16
  41.0%
31
  39.2%
Male
25
  62.5%
23
  59.0%
48
  60.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 39 participants 79 participants
Hispanic or Latino
3
   7.5%
0
   0.0%
3
   3.8%
Not Hispanic or Latino
37
  92.5%
39
 100.0%
76
  96.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 39 participants 79 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
2
   5.1%
2
   2.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   5.0%
1
   2.6%
3
   3.8%
White
37
  92.5%
36
  92.3%
73
  92.4%
More than one race
1
   2.5%
0
   0.0%
1
   1.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months.
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Arm/Group Title Acetylsalicylic Acid Placebo
Hide Arm/Group Description:
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily.
Patients receive oral placebo once daily.
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: micron^-1
Baseline 40.72  (16.91) 37.54  (21.64)
Post Intervention 43.45  (26.84) 37.52  (28.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid, Placebo
Comments The study was powered to detect an attributable change in the aspirin group of 50% relative to baseline values - an approximate 50% increase in spectral slope.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months.
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa
Arm/Group Title Acetylsalicylic Acid Placebo
Hide Arm/Group Description:
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily.
Patients receive oral placebo once daily.
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: unitless
Baseline 142.41  (2570.86) 23.28  (2699.82)
Post Intervention -407.78  (3470.69) 650.97  (3201.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acetylsalicylic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Arm/Group Title Acetylsalicylic Acid Placebo
Hide Arm/Group Description:
Patients receive oral acetylsalicylic acid (aspirin) once daily.
Patients receive oral placebo once daily.
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: Percentage of Total Cells
Baseline 4.56  (4.27) 5.24  (3.69)
At 3 Months 4.26  (4.44) 7.26  (6.77)
4.Secondary Outcome
Title Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Arm/Group Title Acetylsalicylic Acid Placebo
Hide Arm/Group Description:
Patients receive oral acetylsalicylic acid (aspirin) once daily.
Patients receive oral placebo once daily.
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: Percentage of Total Cells
Baseline 38.07  (16.83) 40.45  (12.26)
3 Months Intervention 43.60  (14.77) 37.74  (13.37)
5.Secondary Outcome
Title Rectal Prostaglandin Levels as Measured by ELISA
Hide Description Evaluate the effect of aspirin on rectal prostaglandin levels.
Time Frame 3 months from baseline colonoscopy to end of intervention.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Arm/Group Title Acetylsalicylic Acid Placebo
Hide Arm/Group Description:
Patients receive oral acetylsalicylic acid (aspirin) once daily.
Patients receive oral placebo once daily.
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: pg/ml
Baseline 305.93  (300.01) 654.64  (1536.52)
Post Intervention 211.97  (134.32) 209.02  (134.33)
6.Other Pre-specified Outcome
Title Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Arm/Group Title Acetylsalicylic Acid Placebo
Hide Arm/Group Description:
Patients receive oral acetylsalicylic acid (aspirin) once daily.
Patients receive oral placebo once daily.
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: pg/ml
Baseline 712976.73  (2082413.36) 430109.56  (798782.31)
Post Intervention 6914.87  (20891.41) 200233.5  (463029.1)
Time Frame 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Acetylsalicylic Acid Placebo
Hide Arm/Group Description

Patients receive oral acetylsalicylic acid (aspirin) once daily.

acetylsalicylic acid: Given orally

laboratory biomarker analysis: Correlative study

Patients receive oral placebo once daily.

placebo: Given orally

laboratory biomarker analysis: Correlative study

All-Cause Mortality
Acetylsalicylic Acid Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Acetylsalicylic Acid Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/40 (0.00%)      0/39 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Acetylsalicylic Acid Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/40 (42.50%)      21/39 (53.85%)    
Blood and lymphatic system disorders     
Blood/Bone Marrow: Hemoglobin  1  1/40 (2.50%)  1 1/39 (2.56%)  3
Blood/Bone Marrow: Other  1  1/40 (2.50%)  2 1/39 (2.56%)  1
Hemorrhage with Surgery  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Cardiac disorders     
Hypertension  1  1/40 (2.50%)  1 0/39 (0.00%)  0
Gastrointestinal disorders     
Diarrhea  1  1/40 (2.50%)  1 0/39 (0.00%)  0
Nausea  1  1/40 (2.50%)  1 0/39 (0.00%)  0
Heartburn  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Constitutional Symptoms: Weight Gain  1  0/40 (0.00%)  0 1/39 (2.56%)  2
General disorders     
Pain: Stomach  1  2/40 (5.00%)  2 2/39 (5.13%)  2
Pain: Abdomen Nos  1  2/40 (5.00%)  2 1/39 (2.56%)  2
Pain: Head/Headache  1  1/40 (2.50%)  1 4/39 (10.26%)  4
Pain: Other  1  1/40 (2.50%)  1 1/39 (2.56%)  1
Pain: Joint  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Pain: Extremity - Limb  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Pain: Uterus  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Constitutional Symptoms: Fever  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Constitutional Symptoms: Insomnia  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Constitutional Symptoms: Other  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Immune system disorders     
Rhinitis  1  1/40 (2.50%)  1 0/39 (0.00%)  0
Infections and infestations     
Upper Airway Nos  1  1/40 (2.50%)  1 2/39 (5.13%)  2
Infection - Other  1  0/40 (0.00%)  0 2/39 (5.13%)  2
Metabolism and nutrition disorders     
Metabolic/Lab - Other  1  1/40 (2.50%)  1 1/39 (2.56%)  1
AST  1  1/40 (2.50%)  1 0/39 (0.00%)  0
ALT  1  1/40 (2.50%)  1 0/39 (0.00%)  0
Hypoglycemia  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Hyperkalemia  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Nervous system disorders     
Dizziness  1  0/40 (0.00%)  0 2/39 (5.13%)  2
Renal and urinary disorders     
Cystitis  1  0/40 (0.00%)  0 1/39 (2.56%)  2
Reproductive system and breast disorders     
Sexual - Other  1  0/40 (0.00%)  0 1/39 (2.56%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/40 (2.50%)  1 1/39 (2.56%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v. 3.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Seema Khan
Organization: Northwestern University
Phone: 312-503- 4236
EMail: skhan@nm.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00468910    
Other Study ID Numbers: 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 )
First Submitted: May 2, 2007
First Posted: May 3, 2007
Results First Submitted: December 15, 2015
Results First Posted: May 31, 2017
Last Update Posted: May 31, 2017