Eflornithine and Sulindac in Preventing Colorectal Cancer in Patients With Colon Polyps
- Conditions
- Precancerous Condition
- Interventions
- Registration Number
- NCT00118365
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This randomized phase III trial is studying eflornithine and sulindac to see how well they work compared to a placebo in preventing colorectal cancer in patients with colon polyps. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of eflornithine and sulindac may prevent colorectal cancer. It is not yet known whether eflornithine and sulindac are more effective than a placebo in preventing colorectal cancer
- Detailed Description
PRIMARY OBJECTIVES:
I. Compare the rate of new adenomatous polyp formation in patients with a history of adenomatous polyps of the colon treated with eflornithine and sulindac vs placebo.
II. Correlate the effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa with the rate of new adenoma formation in these patients.
III. Compare the rate of side effects in patients treated with these regimens.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center and aspirin use (yes vs no).
Patients receive oral double placebo once daily for 4 weeks. Patients who are more than 70% compliant by pill measurement or self reporting are randomized to 1 of 2 treatment arms.
Arm I: Patients receive oral double placebo once daily.
Arm II: Patients receive oral eflornithine (DFMO) and oral sulindac once daily.
In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 375
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II (placebo) laboratory biomarker analysis Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy. Arm II (placebo) placebo Patients receive oral double placebo once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy. Arm I (eflornithine and sulindac) laboratory biomarker analysis Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy. Arm I (eflornithine and sulindac) eflornithine Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy. Arm I (eflornithine and sulindac) sulindac Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.
- Primary Outcome Measures
Name Time Method Detection of Any Adenoma at the End of the Study Up to 36 months Detection of any adenoma at the end of the study. This analysis is based on the participants who had the end-of-study colonscopy procedure done.
- Secondary Outcome Measures
Name Time Method Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment Up to 36 months Putrescine responder = Putrescine values at 36-month are decreased by \>=30% from baseline Putrescine nonresponder = Putrescine values at 36-month are increased, or decreased by \< 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
Biomarker in Adenoma: CEA At the end of the study carcino-embryonic antigen (CEA) is adenocarcinoma tissue marker that is expressed during adenoma formation.
Biomarker in Adenoma: Sialyl-TN (B72.3) At the end of the study sialyl-Tn (B72.3) is adenocarcinoma tissue marker that is expressed during adenoma formation.
Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment Up to 36 months This analysis is based on the participants who had the end-of-study colonscopy procedure done and their baseline PGE2 values are available. The low PGE2 is defined as the values that are below the median PGE2 value in the analysis cohort. The high PGE2 is defined as the values that are above the median PGE2 value in the analysis cohort.
Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment Up 36 months The low is defined as the ratios that are below the median spermidine-to-spermine ratio in the analysis cohort. The high is defined as the ratios that are above the median spermidine-to-spermine ratio in the analysis cohort.
In the finalized datasaet, the total number of adnoma detected in the placebo group is 55. The descrepancy in the total number of adnoma detected in placebo group between Outcome Measure 1 and this oucome is due to the revolution of the datatset.
The analysis cohort is based on the participants whose data are available and complete.Baseline Putrescine by ODC Genotype Baseline ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
At the End of the Study - Putrescine Response by ODC Genotype At the end of the study Putrescine responder was defined as (tissue putrescine value at baseline - tissue putrescine value at the end of the study)/(tissue putrescine value at baseline) ≥ the threshold. Putrescine non-responder was defined as (tissue putrescine value at baseline - tissue putrescine value at the end of the study)/(tissue putrescine value at baseline) \< the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.
ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment Up 36 months The low is defined as the values that are below the median putrescine level in the analysis cohort. The high is defined as the values that are above the median putrescine level in the analysis cohort.
Baseline Spermine by ODC Genotype Baseline ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
At the End of the Study - Spermidine Response by ODC Genotype At the end of the study Spermidine responder was defined as (tissue spermidine value at baseline - tissue spermidine value at the end of the study)/(tissue spermidine value at baseline) ≥ the threshold. Spermidine non-responder was defined as (tissue spermidine value at baseline - tissue spermidine value at the end of the study)/(tissue spermidine value at baseline) \< the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.
ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.Number of Participants Have Adenoma Recurrence in Each ODC1 Genotytpe by Treatment Group Up to 36 months ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment Up to 36 months PGE2 Responder = PGE2 values at 36-month are decreased by \>=30% in PGE2 values from baseline PGE2 nonresponder = PGE2 values at 36-month are increased, or decreased by \< 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
Baseline Spermidine by ODC Genotype Baseline ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
Biomarker in Adenoma: Apoptosis At the end of the study Apoptosis expression was assessed using cytoplasmic staining. The definitions for the category level for the Apoptosis are: 1. focal (less than 10% cells that are positively stained); 2. less than 50% cells are positively stained; 3. more than 50% cells are positively stained.
Biomarker in Adenoma: Bcl-2 At the end of the study, up to 3 years bcl-2 is the anti-apoptotic protein BCL2
Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment Up to 36 months Spermidine-to-spermine ratio responder = ratios at 36-month are decreased by \>=30% from baseline Spermidine-to-spermine ratio nonresponder = ratios at 36-month are increased, or decreased by \< 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
Adverse Events With a Grade of 3 and Above Up to 36 months Participants reported at least 1 adverse event with a grade of 3 and above, regardless if the event is defined as serious per protocol or other.
Per protocol, not all grade 3 events are considered as serious events.At the End of the Study - Spermine Response by ODC Genotype At the end of the study Spermine responder was defined as (tissue spermine value at baseline - tissue spermine value at the end of the study)/(tissue spermine value at baseline) ≥ the threshold. Spermine non-responder was defined as (tissue spermine value at baseline - tissue spermine value at the end of the study)/(tissue spermine value at baseline) \< the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.
ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.Biomarker in Adenoma - Ki-67 At the end of the study Estimated mean percent of cells staining postivie for the Ki-67 based on the GEE approach with adjustment for covariates
Biomarker in Adenoma - p53 At the end of the study Estimated mean percent of cells staining postivie for p53 based on GEE approach with adjument for covariates.
Tumor protein p53, also known as p53, cellular tumor antigen p53, phosphoprotein p53, or tumor suppressor p53, is a protein that in humans is encoded by the TP53 gene.
Trial Locations
- Locations (1)
University of California Medical Center At Irvine-Orange Campus
🇺🇸Orange, California, United States