A clinical study of the efficacy of oral alpha-difluoromethylornithine (eflornithine or DFMO) in male and female subjects ages 30-60 with gastric premalignant lesions in two high risk regions of Latin America.
Primary Objective \- The difference in cell DNA damage between patients treated with DFMO and patients treated with placebo at 6 months. The cell DNA damage is measured using the percent positive gastric epithelial cells assessed by IHC for gamma H2AX. The mean difference between the two groups at 6 months will be calculated, accounting for their baseline measurements. Secondary Objectives * The difference in cell DNA damage between patients treated with DFMO and patients treated with placebo for 18 months, and then followed for an additional 6 months. The cell DNA damage is measured using the percent positive gastric epithelial cells assessed by IHC for gamma H2AX. The mean difference between the two groups at 18 and 24 months will be calculated, accounting for their baseline measurements. * The differences in the gastritis histopathology score between patients treated with DFMO and patients treated with placebo for a total of 18 months, and followed for an additional 6 months. The gastritis histopathology score is measured with a quantitative scale 0.0-6.0, for atrophy, intestinal metaplasia, and dysplasia. The mean differences between the two groups at 6, 18, and 24 months will be calculated using mixed models, accounting for their baseline measurements. * Number of patients with quantitative toxicities. Toxicities will be assessed per CTCAE criteria, and each toxicity will be assigned an adverse event (AE) term according to CTCAE definitions (each AE term = unique representation of a specific event used for medical documentation and scientific analyses), and graded as defined by CTCAE (grade 1 = mild; grade 2 = moderate; grade 3 = severe or significant but not immediately life-threatening; grade 4 = life-threatening; grade 5 = death). * To evaluate whether candidate single nucleotide polymorphisms (SNPs) relevant to eflornithine (DFMO) efficacy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
91
Eflornithine\*, 2 tablets, Oral, Daily for 18 months
Eflornithine placebo, 2 tablets, Oral, Daily for 18 months
Ministry of Health, Hospital de Occidente
Copán, Honduras
University of Puerto Rico, Comprehensive Cancer Center
San Juan, Puerto Rico
Gastric Epithelial Cell DNA Damage, at 6 Months Versus Baseline
The cell DNA damage is measured by the percent positive gastric epithelial cells, as assessed by IHC for gamma H2AX. The mean differences at 6 months versus baseline of the percent positive gastric epithelial cells is compared between the two groups.
Time frame: Baseline up to 6 months
Gastric Epithelial Cell DNA Damage, at 18 Months Versus Baseline
The cell DNA damage is measured using the percent positive gastric epithelial cells, as assessed by IHC for gamma H2AX. The mean differences in percent positive gastric epithelial cells at 18 months versus baseline is compared between the two groups.
Time frame: Baseline up to 18 months
Gastric Epithelial Cell DNA Damage, at 24 Months Versus Baseline
The cell DNA damage is measured by the percent positive gastric epithelial cells, as assessed by IHC for gamma H2AX. The mean differences at 24 months versus baseline of the percent positive gastric epithelial cells is compared between the two groups.
Time frame: Baseline up to 24 months
Change in Gastric Histopathology Score, at 6 Months Versus Baseline
The mean differences in the gastric histopathology score at 6 months versus baseline are calculated, with comparison of the eflornithine and placebo groups. The changes in histology stage are assessed with the validated Correa Histopathology Score system (ranges represent differences in severity and extent): normal mucosa 1, non-atrophic gastritis 2, multifocal atrophic gastritis without intestinal metaplasia 3.25-4.0, gastric intestinal metaplasia 4.3-5.0, dysplasia 5.25-5.75, and cancer 6. The Correa Histopathology Score is based upon the Updated Sydney System biopsy protocol (5 biopsies). The most advanced lesion (highest Correa score) in the stomach represents the summary Correa score for the patient at the given time point.
Time frame: Baseline up to 6 months
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Change in Gastric Histology Score, at 18 Months Versus Baseline
The mean differences in the gastric histopathology score at 18 months versus baseline are calculated, with comparison of the eflornithine and placebo groups. The changes in histology stage are assessed with the validated Correa Histopathology Score system (ranges represent differences in severity and extent): normal mucosa 1, non-atrophic gastritis 2, multifocal atrophic gastritis without intestinal metaplasia 3.25-4.0, gastric intestinal metaplasia 4.3-5.0, dysplasia 5.25-5.75, and cancer 6. The Correa Histopathology Score is based upon the Updated Sydney System biopsy protocol (5 biopsies). The most advanced lesion (highest Correa score) in the stomach represents the summary Correa score for the patient at the given time point.
Time frame: Baseline up to 18 months
Change in Gastric Histology Score, at 24 Months Versus Baseline
The mean differences in the gastric histopathology score at 24 months versus baseline are calculated, with comparison of the eflornithine and placebo groups. The changes in histology stage are assessed with the validated Correa Histopathology Score system (ranges represent differences in severity and extent): normal mucosa 1, non-atrophic gastritis 2, multifocal atrophic gastritis without intestinal metaplasia 3.25-4.0, gastric intestinal metaplasia 4.3-5.0, dysplasia 5.25-5.75, and cancer 6. The Correa Histopathology Score is based upon the Updated Sydney System biopsy protocol (5 biopsies). The most advanced lesion (highest Correa score) in the stomach represents the summary Correa score for the patient at the given time point.
Time frame: Baseline up to 24 months