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Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT00983580
Recruitment Status : Completed
First Posted : September 24, 2009
Results First Posted : April 30, 2018
Last Update Posted : September 4, 2019
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
Condition Adenomatous Polyp
Interventions Drug: Aspirin
Drug: Eflornithine
Other: Laboratory Biomarker Analysis
Other: Placebo
Other: Telephone-Based Intervention
Enrollment 107
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Hide Arm/Group Description Patients receive 325 mg acetylsalicylic acid PO once daily and 500 mg eflornithine PO once daily on days 1-28. Patients receive corresponding placebo PO daily on days 1-28.
Period Title: Overall Study
Started 54 53
Completed 49 49
Not Completed 5 4
Reason Not Completed
Cancel Prior to treatment             1             3
Protocol Violation             1             1
Ineligible             3             0
Arm/Group Title Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo) Total
Hide Arm/Group Description Patients receive 325 mg acetylsalicylic acid PO once daily and 500 mg eflornithine PO daily on days 1-28. Patients receive corresponding placebo PO daily on days 1-28. Total of all reporting groups
Overall Number of Baseline Participants 49 49 98
Hide Baseline Analysis Population Description
All eligible patients that began protocol treatment were included in this analysis. Patients who cancelled prior to treatment, violations and ineligible patients were excluded.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 49 participants 49 participants 98 participants
62
(46 to 83)
62
(50 to 79)
62
(46 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 49 participants 98 participants
Female
26
  53.1%
19
  38.8%
45
  45.9%
Male
23
  46.9%
30
  61.2%
53
  54.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 49 participants 49 participants 98 participants
49
 100.0%
49
 100.0%
98
 100.0%
1.Primary Outcome
Title Adenoma Recurrence Rate for the Treatment Arm Relative to Placebo
Hide Description The primary endpoint is the proportion of participants with an adenoma recurrence at the 1-year follow-up colonoscopy exam. All eligible, randomized participants who have signed a consent form and received at least one follow-up endoscopy exam will be considered evaluable for the primary endpoint. This adenoma recurrence rate for DFMO + aspirin will be compared to double placebo to see if there is improvement in the adenoma recurrence rate in this patient population. A 1-sided Chi-square test was used to determine if there was a significant difference between treatment arms.
Time Frame At 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
On Arm 1, 1 patient cancelled prior to treatment, 1 was a violation, 3 were deemed ineligible, and 7 patients did not receive a follow-up endoscopy. On Arm 2, 3 patients cancelled prior to treatment, 1 was a violation, and 6 did not receive a follow-up endoscopy.
Arm/Group Title Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Hide Arm/Group Description:
Patients receive 325 mg acetylsalicylic acid PO once daily and 500 mg eflornithine PO daily on days 1-28.
Patients receive corresponding placebo PO daily on days 1-28.
Overall Number of Participants Analyzed 42 43
Measure Type: Number
Unit of Measure: proportion of participants
0.595 0.581
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Acetylsalicylic Acid and Eflornithine), Arm II (Placebo)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.448
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Secondary Outcome
Title ACF Characteristics vs Adenoma Recurrence Rate
Hide Description A potential surrogate endpoint biomarker is the aberrant crypt focus (ACF). ACF are the earliest lesions that can be detected in colorectal mucosa and are believed to be precursors of adenomas and cancers. At the 1-year time point, the presence of adenoma recurrence and the number of ACF sites was recorded for each patient. The percent change in ACF number was calculated as the number of ACF present at the 1-year post-intervention exam minus the baseline number of ACF, divided by the number of ACF present at baseline. A negative score represents a loss in the number of sites and a positive number indicates an increase in the number of ACF sites. Therefore, the possible range in percent change cannot be lower than -100% and has no upper bound. A Wilcoxon Rank-sum test was used to assess the relationship between ACF percent change and adenoma recurrence rate. This analysis was only conducted in those participants who had at least 5 rectal ACF at baseline.
Time Frame At baseline and 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that were eligible, treated, analyzed for ACF at baseline and 12-months, and had 5 or more ACF at baseline were included in this analysis.
Arm/Group Title All Patients
Hide Arm/Group Description:
Patients from Arm I and Arm II were combined in this analysis
Overall Number of Participants Analyzed 62
Median (Full Range)
Unit of Measure: percentage of change in ACF number
No Adenoma Recurrence at 12 months Number Analyzed 25 participants
-20.8
(-89.5 to 237.5)
Adenoma Recurrence at 12 months Number Analyzed 37 participants
-45.0
(-100 to 300)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Patients
Comments This statistical analysis compares the difference between the number of patients with No adenoma recurrence at 12 months with those with adenoma recurrence at 12 months.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.358
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Characterization of ACF
Hide Description A potential surrogate endpoint biomarker is the aberrant crypt focus (ACF). ACF are the earliest lesions that can be detected in colorectal mucosa and are believed to be precursors of adenomas and cancers. The number and total size of ACF sites may serve as risk markers for adenoma/carcinoma development. The median number of ACF sites per patient were collected prior to treatment.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 49 eligible patients receiving treatment in Arm I, 2 patients did not have ACF analysis done. The same number of patients of patients did not have ACF done in Arm II.
Arm/Group Title Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Hide Arm/Group Description:
Patients receive 325 mg acetylsalicylic acid PO once daily and 500 mg eflornithine PO daily on days 1-28.
Patients receive corresponding placebo PO daily on days 1-28.
Overall Number of Participants Analyzed 47 47
Median (Full Range)
Unit of Measure: number of ACF sites
11
(0 to 42)
7
(0 to 31)
4.Secondary Outcome
Title Comparison of the Percent Change in ACF Number Across the 2 Treatment Arms
Hide Description The number of ACF sites per patient was collected at baseline and at 1-year time points. The percent change in ACF number was calculated as the number of ACF present at the 12-month post-intervention exam minus the baseline number of ACF, divided by the number of ACF present at baseline. A negative score represents a loss in the number of sites from baseline to year 1 post-treatment. A positive number indicates an increase in the number of ACF sites. Therefore, the possible range in percent change cannot be lower than -100% and has no upper bound. The percent change in ACF number between arms was compared using a t-test.
Time Frame At baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible treated patients that were assessed for ACF at baseline and after 1-year of treatment were included in this analysis.
Arm/Group Title Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Hide Arm/Group Description:
Patients receive 325 mg acetylsalicylic acid PO once daily and 500 mg eflornithine PO daily on days 1-28.
Patients receive corresponding placebo PO daily on days 1-28.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: percentage of change in ACF number
-28.6  (51.1) 10.6  (97.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Acetylsalicylic Acid and Eflornithine), Arm II (Placebo)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.513
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Safety, Tolerability, and Adverse Events of Study Treatment
Hide Description The National Cancer Institute (NCI) Common Terminology Criteria (CTC) Version 3.0 was used to grade all adverse events. The number of patients reporting a grade 3 or higher event are tabulated here. A grade 3 event is one categorized as being severe or medically significant but not immediately life-threatening. A grade 4 is considered life-threatening, and a grade 5 is death related to the event. A complete list of all adverse events is given in the Adverse Events section.
Time Frame Up to 48 months from beginning treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
On Arm 1, 1 patient cancelled prior to treatment, 1 was a violation, 3 were deemed ineligible. On Arm 2, 3 were ineligible, 1 was a violation. All other patients were treated and evaluated for toxicity and included in this evaluation.
Arm/Group Title Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Hide Arm/Group Description:
Patients receive 325 mg acetylsalicylic acid PO once daily and 500 mg eflornithine PO daily on days 1-28.
Patients receive corresponding placebo PO daily on days 1-28.
Overall Number of Participants Analyzed 49 49
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3 Adverse Event
0
   0.0%
3
   6.1%
Grade 4 Adverse Event
0
   0.0%
0
   0.0%
6.Other Pre-specified Outcome
Title Effect of the Study Drugs and Placebo With Respect to Biomarkers
Hide Description For continuous variables, we will use the 2-sample t-test (or nonparametric equivalent) to compare the active arm to the placebo arm. For categorical data, we will explore the relationship between the treatment arms and biomarkers with chi-square or fisher's exact tests. Correlations will be sought between caspase-3 staining, proliferative indices and their ratio, as well as other biomarkers using a chi-square test.
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for this endpoint.
Arm/Group Title All Patients
Hide Arm/Group Description:
Patients from Arm I and Arm II were combined in this analysis
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Other Pre-specified Outcome
Title Gene Expression Analysis
Hide Description Differences in log-transformed values among ACF or patient characteristics will be compared using t tests or analysis of variance (ANOVAs).
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for this endpoint.
Arm/Group Title Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Hide Arm/Group Description:
Patients receive 325 mg acetylsalicylic acid PO once daily and 500 mg eflornithine PO daily on days 1-28.
Patients receive corresponding placebo PO daily on days 1-28.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events were collected at the end of each 28 day cycle, for up to 1 year. All patients that received treatment and were assessed for adverse events are included in this section of the report. There was 1 patient cancel and 1 patient not evaluated for adverse events, leaving 52 patients. In Arm 2, there were 3 cancels which left 50 patients evaluated for adverse events.
 
Arm/Group Title Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Hide Arm/Group Description Patients receive 325 mg acetylsalicylic acid PO once daily and 500 mg eflornithine PO daily on days 1-28. Patients receive corresponding placebo PO daily on days 1-28.
All-Cause Mortality
Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/52 (0.00%)      0/50 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/52 (0.00%)      1/50 (2.00%)    
Blood and lymphatic system disorders     
Thrombosis * 1  0/52 (0.00%)  0 1/50 (2.00%)  1
1
Term from vocabulary, MedDRA (10.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I (Acetylsalicylic Acid and Eflornithine) Arm II (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/52 (7.69%)      4/50 (8.00%)    
Ear and labyrinth disorders     
Hearing test abnormal  1  1/52 (1.92%)  1 1/50 (2.00%)  1
Tinnitus  1  2/52 (3.85%)  7 4/50 (8.00%)  9
Gastrointestinal disorders     
Abdominal pain  1  0/52 (0.00%)  0 1/50 (2.00%)  1
Diarrhea  1  0/52 (0.00%)  0 1/50 (2.00%)  1
Gastrointestinal disorder  1  1/52 (1.92%)  1 0/50 (0.00%)  0
Nausea  1  0/52 (0.00%)  0 1/50 (2.00%)  1
Rectal hemorrhage  1  1/52 (1.92%)  1 0/50 (0.00%)  0
Rectal pain  1  1/52 (1.92%)  1 0/50 (0.00%)  0
General disorders     
Pain  1  1/52 (1.92%)  1 0/50 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Musculoskeletal disorder  1  1/52 (1.92%)  1 0/50 (0.00%)  0
Nervous system disorders     
Dizziness  1  1/52 (1.92%)  1 0/50 (0.00%)  0
Headache  1  1/52 (1.92%)  1 1/50 (2.00%)  1
1
Term from vocabulary, MedDRA 10
Indicates events were collected by systematic assessment
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: Frank A. Sinicrope, M.D.
Organization: Mayo Clinic
EMail: sinicrope.frank@mayo.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00983580     History of Changes
Obsolete Identifiers: NCT01647126
Other Study ID Numbers: NCI-2009-01192
NCI-2009-01192 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
09-001758
MC054A ( Other Identifier: Mayo Clinic )
R01CA113681 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
First Submitted: September 23, 2009
First Posted: September 24, 2009
Results First Submitted: February 20, 2018
Results First Posted: April 30, 2018
Last Update Posted: September 4, 2019