Chemoprevention of Gastric Carcinogenesis

Targeted Chemoprevention of Gastric Carcinogenesis in High Risk Populations

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric Cancer; Gastric Intestinal Metaplasia
• Intervention / Treatment: Drug: Eflornithine; Other: Eflornithine placebo

Detailed Description

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
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• Honduras
  • Copán, Honduras
    • Ministry of Health, Hospital de Occidente
• Puerto Rico
  • San Juan, Puerto Rico
    • University of Puerto Rico, Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have a history of a premalignant lesion of the stomach, atrophic gastritis or intestinal metaplasia
• Patients must have a pure tone audiometry evaluation to document air conduction within 60 days prior to randomization.

• Patients must have adequate blood counts as evidenced by the following results (obtained within 60 days):

  • Blood counts: WBC ≥4.0 /mcL, platelets ≥100,000 /mcL and hemoglobin ≥11.0 g/dL
  • Kidney function: Creatinine <1.6 x IULN (institutional upper limit of normal)
  • Liver function tests: Bilirubin ≤2.0 mg/dL and AST (SGOT) or ALT (SGPT) ≤2 x IULN

Exclusion Criteria:

• Subjects with dysplasia (indeterminate, low grade, high grade) are not eligible for participation
• Patients must not have a significant medical or psychiatric condition that would preclude study completion.
• Patients with hearing loss ≥30 dB in any of the tested frequencies (250 Hz, 500 Hz, 1,000 Hz, 2,000 Hz, 4,000 Hz, 8,000 Hz) are not eligible.
• Patients must not have known hypersensitivity to eflornithine or the excipients.
• Patients must not be receiving corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulants on a regular or intermittent basis.
• Patients must not have a significant cardiovascular disease history, including uncontrolled blood pressure (sBP > 150 mmHg), myocardial infarction, cerebrovascular accident, or heart failure (New York Heart Association Class III, or IV).
• Patients must not have a history of gastric or esophageal cancer, gastric resection or surgery, peptic ulcer disease (within 6 months), H. pylori treatment (within 6 months), or inflammatory bowel disease.
• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for >5 years.
• Patients must not be receiving corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulants on a regular or intermittent basis.
• Patients must not be pregnant or nursing (due to eflornithine pregnancy class C). Women and men of reproductive potential must have agreed to use an effective contraceptive method.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Eflornithine	Drug: Eflornithine; Eflornithine*, 2 tablets, Oral, Daily for 18 months
Placebo Comparator: Eflornithine Placebo	Other: Eflornithine placebo; Eflornithine placebo, 2 tablets, Oral, Daily for 18 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Difference in Cell DNA Damage, Based on Percent Positive Cells, 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.	at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	at 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.	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.	at 6, 18 and 24 months
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).	at 6, 18, and 24 months

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI); Cancer Prevention Pharmaceuticals, Inc.
• Investigators: Study Chair: Doug Morgan, MD, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer enter; Principal Investigator: Keith Wilson, MD, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer enter

Publications and helpful links

Helpful Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2016
• Primary Completion (Actual): December 20, 2022
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 20, 2016
• First Submitted That Met QC Criteria: June 8, 2016
• First Posted (Estimated): June 9, 2016

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Gastric adenocarcinoma; Atrophic gastritis; Gastric intestinal metaplasia; Gastric premalignant lesion
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Carcinogenesis; Metaplasia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Trypanocidal Agents; Ornithine Decarboxylase Inhibitors; Eflornithine
• Other Study ID Numbers: VICC GI 1527; 6R01CA190612-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO