Precancerous Condition
Conditions
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.
Interventions
OTHERplacebo
Given orally
DRUGeflornithine
Given orally
DRUGsulindac
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Criteria: * History of \>= 1 surgically resected adenomatous polyp of the colon measuring \>= 3 mm within the past 5 years * Screening colonoscopy performed within the past 6 months * All polyps must have been removed during colonoscopy, pathologically examined, and archived * No prior surgical resection removing \> 40 cm of the colon * No personal or family history of familial polyposis or hereditary non-polyposis colon cancer * SWOG 0-1 * Bilirubin =\< 2.0 mg/dL * AST and ALT =\< 2 times normal * Creatinine =\< 1.5 mg/dL * Urine protein =\<, urine casts 0-3, urine WBC and RBC count 0-5 cells by urinalysis * No history of inflammatory bowel disease * No gastric or duodenal ulcers within the past 12 months * Gastric or duodenal ulcers that were adequately treated \> 24 months ago are allowed * No symptomatic gastric or duodenal ulcers * Not pregnant or nursing * Negative pregnancy test * Must have regional geographic stability over the next 36 months * Pure tone audiometry evaluation normal * Patients with \>= 20 dB of uncorrectable hearing loss (for age) of any 2 contiguous frequencies are not allowed * No invasive malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, level I (or Breslow \< 0.76 mm) cutaneous melanoma, Duke's A colon cancer, stage I cervical cancer, or stage 0 chronic lymphocytic leukemia * No severe metabolic disorder * No other significant acute or chronic disease that would preclude study participation * No history of abnormal wound healing or repair * No conditions that would confer risk of abnormal wound healing or repair * No history of allergy to NSAIDs or eflornithine * No concurrent chemotherapy * No concurrent corticosteroids on a regular or predictable intermittent basis * No concurrent radiotherapy * Concurrent calcium supplements (=\< 1,000 mg/day) allowed * Concurrent lipid-lowering drugs (i.e., high-dose statins) allowed * No other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) on a regular or predictable intermittent basis * Concurrent aspirin for cardiovascular prophylaxis (i.e., 81 mg/day) allowed * No concurrent anticoagulants on a regular or predictable intermittent basis * No concurrent treatment for gastric or duodenal ulcers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 - 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: 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. |
| 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. |
| Biomarker in Adenoma: Bcl-2 | At the end of the study, up to 3 years | bcl-2 is the anti-apoptotic protein BCL2 |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Eflornithine and 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.
eflornithine: Given orally
sulindac: Given orally
laboratory biomarker analysis: Correlative studies | 191 |
| Arm II (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.
placebo: Given orally
laboratory biomarker analysis: Correlative studies | 184 |
| Total | 375 |
Baseline characteristics
| Characteristic | Arm I (Eflornithine and Sulindac) | Arm II (Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 8.6 | 61 years STANDARD_DEVIATION 8.4 | 60.5 years STANDARD_DEVIATION 8.4 |
| Sex: Female, Male Female | 44 Participants | 46 Participants | 90 Participants |
| Sex: Female, Male Male | 147 Participants | 138 Participants | 285 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 173 / 191 | 154 / 184 |
| serious Total, serious adverse events | 41 / 191 | 28 / 184 |
Outcome results
Primary
Detection of Any Adenoma at the End of the Study
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.
Time frame: Up to 36 months
Population: This analysis is based on the participants who had the end-of-study colonscopy procedure done.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study | Yes | 17 participants |
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study | No | 121 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study | No | 76 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study | Yes | 53 participants |
Secondary
Adverse Events With a Grade of 3 and Above
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.
Time frame: Up to 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Eflornithine and Sulindac) | Adverse Events With a Grade of 3 and Above | 46 participants |
| Arm II (Placebo) | Adverse Events With a Grade of 3 and Above | 37 participants |
Secondary
At the End of the Study - Putrescine Response by ODC Genotype
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.
Time frame: At the end of the study
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | At the End of the Study - Putrescine Response by ODC Genotype | Responder | 26 participants |
| Arm I (Eflornithine and Sulindac) | At the End of the Study - Putrescine Response by ODC Genotype | Non-Responder | 32 participants |
| Arm II (Placebo) | At the End of the Study - Putrescine Response by ODC Genotype | Non-Responder | 19 participants |
| Arm II (Placebo) | At the End of the Study - Putrescine Response by ODC Genotype | Responder | 21 participants |
| Placebo + Low PGE2 at Baseline | At the End of the Study - Putrescine Response by ODC Genotype | Responder | 12 participants |
| Placebo + Low PGE2 at Baseline | At the End of the Study - Putrescine Response by ODC Genotype | Non-Responder | 31 participants |
| Placebo + High PGE2 at Baseline | At the End of the Study - Putrescine Response by ODC Genotype | Responder | 12 participants |
| Placebo + High PGE2 at Baseline | At the End of the Study - Putrescine Response by ODC Genotype | Non-Responder | 37 participants |
Secondary
At the End of the Study - Spermidine Response by ODC Genotype
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.
Time frame: At the end of the study
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | At the End of the Study - Spermidine Response by ODC Genotype | Responder | 25 participants |
| Arm I (Eflornithine and Sulindac) | At the End of the Study - Spermidine Response by ODC Genotype | Non-Responder | 32 participants |
| Arm II (Placebo) | At the End of the Study - Spermidine Response by ODC Genotype | Non-Responder | 28 participants |
| Arm II (Placebo) | At the End of the Study - Spermidine Response by ODC Genotype | Responder | 12 participants |
| Placebo + Low PGE2 at Baseline | At the End of the Study - Spermidine Response by ODC Genotype | Responder | 15 participants |
| Placebo + Low PGE2 at Baseline | At the End of the Study - Spermidine Response by ODC Genotype | Non-Responder | 28 participants |
| Placebo + High PGE2 at Baseline | At the End of the Study - Spermidine Response by ODC Genotype | Responder | 11 participants |
| Placebo + High PGE2 at Baseline | At the End of the Study - Spermidine Response by ODC Genotype | Non-Responder | 38 participants |
Secondary
At the End of the Study - Spermine Response by ODC Genotype
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.
Time frame: At the end of the study
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | At the End of the Study - Spermine Response by ODC Genotype | Non-Responder | 51 participants |
| Arm I (Eflornithine and Sulindac) | At the End of the Study - Spermine Response by ODC Genotype | Responder | 7 participants |
| Arm II (Placebo) | At the End of the Study - Spermine Response by ODC Genotype | Responder | 7 participants |
| Arm II (Placebo) | At the End of the Study - Spermine Response by ODC Genotype | Non-Responder | 33 participants |
| Placebo + Low PGE2 at Baseline | At the End of the Study - Spermine Response by ODC Genotype | Non-Responder | 25 participants |
| Placebo + Low PGE2 at Baseline | At the End of the Study - Spermine Response by ODC Genotype | Responder | 18 participants |
| Placebo + High PGE2 at Baseline | At the End of the Study - Spermine Response by ODC Genotype | Non-Responder | 39 participants |
| Placebo + High PGE2 at Baseline | At the End of the Study - Spermine Response by ODC Genotype | Responder | 10 participants |
Secondary
Baseline Putrescine by ODC Genotype
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.
Time frame: Baseline
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Eflornithine and Sulindac) | Baseline Putrescine by ODC Genotype | 0.47 nmol/mg protein |
| Arm II (Placebo) | Baseline Putrescine by ODC Genotype | 0.56 nmol/mg protein |
Secondary
Baseline Spermidine by ODC Genotype
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.
Time frame: Baseline
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Eflornithine and Sulindac) | Baseline Spermidine by ODC Genotype | 1.99 nmol/mg protein |
| Arm II (Placebo) | Baseline Spermidine by ODC Genotype | 2.17 nmol/mg protein |
Secondary
Baseline Spermine by ODC Genotype
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.
Time frame: Baseline
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Eflornithine and Sulindac) | Baseline Spermine by ODC Genotype | 6.82 nmol/mg protein |
| Arm II (Placebo) | Baseline Spermine by ODC Genotype | 7.29 nmol/mg protein |
Secondary
Biomarker in Adenoma: Apoptosis
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.
Time frame: At the end of the study
Population: The analysis cohort is based on the participants whose data are available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Apoptosis | A pattern equal to normal mucosa | 2 adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Apoptosis | 1.focal (<10%) | 7 adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Apoptosis | 2.cyto less than 50% | 1 adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Apoptosis | 3.cyto more than 50% | 2 adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Apoptosis | 3.cyto more than 50% | 13 adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Apoptosis | A pattern equal to normal mucosa | 4 adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Apoptosis | 2.cyto less than 50% | 23 adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Apoptosis | 1.focal (<10%) | 20 adenoma |
Secondary
Biomarker in Adenoma: Bcl-2
bcl-2 is the anti-apoptotic protein BCL2
Time frame: At the end of the study, up to 3 years
Population: The analysis cohort is based on the participants whose data are available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Bcl-2 | 1.<10% of the cells in the adenoma showed staining | 4 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Bcl-2 | 2.10-50% cells showed staining | 3 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Bcl-2 | 3.>50% cells showed staining | 1 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Bcl-2 | A pattern equal to normal mucosa | 4 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Bcl-2 | Insufficient tissue | 0 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Bcl-2 | Insufficient tissue | 2 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Bcl-2 | 1.<10% of the cells in the adenoma showed staining | 25 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Bcl-2 | A pattern equal to normal mucosa | 17 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Bcl-2 | 2.10-50% cells showed staining | 14 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Bcl-2 | 3.>50% cells showed staining | 8 Adenoma |
Secondary
Biomarker in Adenoma: CEA
carcino-embryonic antigen (CEA) is adenocarcinoma tissue marker that is expressed during adenoma formation.
Time frame: At the end of the study
Population: The analysis cohort is based on the participants whose data are available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: CEA | 1.<50% of cells showed staining | 5 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: CEA | 3.>90% of cells showed staining | 0 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: CEA | A pattern equal to normal mucosa | 1 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: CEA | Insufficient tissue | 0 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: CEA | 2.50-90% of cells showed staining | 6 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: CEA | Insufficient tissue | 2 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: CEA | 1.<50% of cells showed staining | 15 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: CEA | 2.50-90% of cells showed staining | 35 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: CEA | 3.>90% of cells showed staining | 9 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: CEA | A pattern equal to normal mucosa | 5 Adenoma |
Secondary
Biomarker in Adenoma - Ki-67
Estimated mean percent of cells staining postivie for the Ki-67 based on the GEE approach with adjustment for covariates
Time frame: At the end of the study
Population: The analysis cohort is based on the participants whose data are available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma - Ki-67 | 59.5 percentage of cells that are positive |
| Arm II (Placebo) | Biomarker in Adenoma - Ki-67 | 63.9 percentage of cells that are positive |
Secondary
Biomarker in Adenoma - p53
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.
Time frame: At the end of the study
Population: The analysis cohort is based on the participants whose data are available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma - p53 | 75.6 percentage of cells that are positive |
| Arm II (Placebo) | Biomarker in Adenoma - p53 | 70.3 percentage of cells that are positive |
Secondary
Biomarker in Adenoma: Sialyl-TN (B72.3)
sialyl-Tn (B72.3) is adenocarcinoma tissue marker that is expressed during adenoma formation.
Time frame: At the end of the study
Population: The analysis cohort is based on the participants whose data are available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Sialyl-TN (B72.3) | 1.<10% of the cells in the adenoma showed staining | 7 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Sialyl-TN (B72.3) | 3.>50% cells showed staining | 0 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Sialyl-TN (B72.3) | 2.10-50% cells showed staining | 2 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Sialyl-TN (B72.3) | Insufficient tissue | 0 Adenoma |
| Arm I (Eflornithine and Sulindac) | Biomarker in Adenoma: Sialyl-TN (B72.3) | a pattern equal to normal mucosa | 3 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Sialyl-TN (B72.3) | Insufficient tissue | 1 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Sialyl-TN (B72.3) | a pattern equal to normal mucosa | 11 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Sialyl-TN (B72.3) | 1.<10% of the cells in the adenoma showed staining | 32 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Sialyl-TN (B72.3) | 2.10-50% cells showed staining | 17 Adenoma |
| Arm II (Placebo) | Biomarker in Adenoma: Sialyl-TN (B72.3) | 3.>50% cells showed staining | 5 Adenoma |
Secondary
Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment
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.
Time frame: Up to 36 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment | Yes | 12 participants |
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment | No | 41 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment | No | 41 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment | Yes | 3 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment | Yes | 19 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment | No | 23 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment | Yes | 21 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment | No | 32 participants |
Secondary
Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment
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.
Time frame: Up 36 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment | Yes | 7 participants |
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment | No | 63 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment | No | 56 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment | Yes | 10 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment | No | 38 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment | Yes | 24 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment | Yes | 31 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment | No | 36 participants |
Secondary
Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment
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.
Time frame: Up 36 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment | Yes | 5 participants |
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment | No | 59 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment | No | 60 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment | Yes | 12 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment | No | 37 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment | Yes | 31 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment | No | 37 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment | Yes | 24 participants |
Secondary
Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment
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.
Time frame: Up to 36 months
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment | Yes | 1 participants |
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment | No | 10 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment | No | 27 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment | Yes | 8 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment | Yes | 4 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment | No | 13 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment | Yes | 15 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment | No | 17 participants |
Secondary
Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment
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.
Time frame: Up to 36 months
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment | Yes | 9 participants |
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment | No | 52 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment | No | 53 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment | Yes | 7 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment | Yes | 22 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment | No | 24 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment | Yes | 28 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment | No | 44 participants |
Secondary
Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment
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.
Time frame: Up to 36 months
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment | Yes | 8 participants |
| Arm I (Eflornithine and Sulindac) | Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment | No | 75 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment | Yes | 8 participants |
| Arm II (Placebo) | Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment | No | 30 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment | No | 24 participants |
| Placebo + Low PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment | Yes | 17 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment | No | 44 participants |
| Placebo + High PGE2 at Baseline | Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment | Yes | 33 participants |
Secondary
Number of Participants Have Adenoma Recurrence in Each ODC1 Genotytpe by Treatment Group
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.
Time frame: Up to 36 months
Population: The analysis cohort is based on the participants whose data are available and complete.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Eflornithine and Sulindac) | Number of Participants Have Adenoma Recurrence in Each ODC1 Genotytpe by Treatment Group | 7 participants |
| Arm II (Placebo) | Number of Participants Have Adenoma Recurrence in Each ODC1 Genotytpe by Treatment Group | 9 participants |
| Placebo + Low PGE2 at Baseline | Number of Participants Have Adenoma Recurrence in Each ODC1 Genotytpe by Treatment Group | 22 participants |
| Placebo + High PGE2 at Baseline | Number of Participants Have Adenoma Recurrence in Each ODC1 Genotytpe by Treatment Group | 18 participants |