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Chemoprevention of Gastric Carcinogenesis

Primary Purpose

Gastric Cancer, Gastric Intestinal Metaplasia

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Eflornithine
Eflornithine placebo
Sponsored by
Vanderbilt-Ingram Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Gastric Cancer focused on measuring Gastric adenocarcinoma, Gastric intestinal metaplasia, Atrophic gastritis, Gastric premalignant lesion

Eligibility Criteria

30 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ministry of Health, Hospital de Occidente
  • University of Puerto Rico, Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Eflornithine

Eflornithine Placebo

Arm Description

Outcomes

Primary Outcome Measures

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 Outcome Measures

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).

Full Information

First Posted
May 20, 2016
Last Updated
June 2, 2023
Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI), Cancer Prevention Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02794428
Brief Title
Chemoprevention of Gastric Carcinogenesis
Official Title
Targeted Chemoprevention of Gastric Carcinogenesis in High Risk Populations
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 19, 2016 (Actual)
Primary Completion Date
December 20, 2022 (Actual)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI), Cancer Prevention Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Gastric Intestinal Metaplasia
Keywords
Gastric adenocarcinoma, Gastric intestinal metaplasia, Atrophic gastritis, Gastric premalignant lesion

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eflornithine
Arm Type
Active Comparator
Arm Title
Eflornithine Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Eflornithine
Intervention Description
Eflornithine*, 2 tablets, Oral, Daily for 18 months
Intervention Type
Other
Intervention Name(s)
Eflornithine placebo
Intervention Description
Eflornithine placebo, 2 tablets, Oral, Daily for 18 months
Primary Outcome Measure Information:
Title
The difference in cell DNA damage between patients treated with DFMO and patients treated with placebo at 6 months.
Description
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.
Time Frame
at 6 months
Secondary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
at 18 and 24 months
Title
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.
Description
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.
Time Frame
at 6, 18 and 24 months
Title
Number of patients with quantitative toxicities.
Description
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).
Time Frame
at 6, 18, and 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Doug Morgan, MD
Organizational Affiliation
Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer enter
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Keith Wilson, MD
Organizational Affiliation
Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer enter
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ministry of Health, Hospital de Occidente
City
Copán
Country
Honduras
Facility Name
University of Puerto Rico, Comprehensive Cancer Center
City
San Juan
Country
Puerto Rico

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.vicc.org/ct/
Description
Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

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Chemoprevention of Gastric Carcinogenesis

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