Chemoprevention of Gastric Carcinogenesis

Gastric Cancer Clinical Trial

Official title:

Targeted Chemoprevention of Gastric Carcinogenesis in High Risk Populations

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02794428
• Other study ID #: VICC GI 1527
• Secondary ID: 6R01CA190612-03
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 19, 2016
• Est. completion date: July 1, 2024

Study information

• Verified date: April 2024
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 91
• Est. completion date: July 1, 2024
• Est. primary completion date: December 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 69 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinogenesis
• Gastric Cancer
• Gastric Intestinal Metaplasia
• Metaplasia

Intervention

Drug:
• Eflornithine
Eflornithine*, 2 tablets, Oral, Daily for 18 months

Other:
• Eflornithine placebo
Eflornithine placebo, 2 tablets, Oral, Daily for 18 months

Locations

Country	Name	City	State
Honduras	Ministry of Health, Hospital de Occidente	Copán
Puerto Rico	University of Puerto Rico, Comprehensive Cancer Center	San Juan

Sponsors (3)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	Cancer Prevention Pharmaceuticals, Inc., National Cancer Institute (NCI)

Countries where clinical trial is conducted

Honduras,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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

External Links

•   Vanderbilt-Ingram Cancer Center, Find a Clinical Trial