Clinical Trial: Chemoprevention of Gastric Carcinogenesis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Targeted Chemoprevention of Gastric Carcinogenesis in High Risk Populations

Brief Summary: 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.

Detailed Summary: The primary intervention is the randomized, double-blind assignment of patients to once daily eflornithine (500 mg) versus placebo for an 18 month treatment period. Gastric precancerous lesions are defined as chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). Patients will be clinically assessed with endoscopy and gastric biopsy at four time points: 0, 6, 18, and 24 months. The assessments at 0 and 24 months are considered part of usual clinical care in subjects with precancerous lesions in high risk regions. Overall, the efficacy of eflornithine is assessed by its effect on: 1) DNA damage, and 2) histology scoring.
Sponsor: Vanderbilt-Ingram Cancer Center

Current Primary Outcome: The difference in cell DNA damage between patients treated with DFMO and patients treated with placebo at 6 months. [ Time Frame: at 6 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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. [ Time Frame: at 18 and 24 months ]
  The cell DNA damage is measured using the percent positive cells assessed by quantitative 8-OHdG immunohistochemistry (IHC). The mean difference between the two groups at 18 and 24 months will be calculated, accounting for their baseline measurements.The additional measure of DNA damage (gamma H2AX by IHC and by flow cytometry will also be assessed at 0, 6, 18, and 24 months).
• 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. [ Time Frame: at 6, 18 and 24 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. [ Time Frame: at 6, 18, and 24 months ]
  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).

Original Secondary Outcome:

• 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. [ Time Frame: at 18 and 24 months ]
  The cell DNA damage is measured using the percent positive cells assessed by quantitative 8-OHdG immunohistochemistry (IHC). 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. [ Time Frame: at 6, 18 and 24 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. [ Time Frame: at 6, 18, and 24 months ]
  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).

Dates:
Date Received: May 20, 2016
Date Started: September 19, 2016
Date Completion: June 30, 2019
Last Updated: May 15, 2017
Last Verified: May 2017