Gastric Cancer, Gastric Intestinal Metaplasia
Conditions
Keywords
Gastric adenocarcinoma, Gastric intestinal metaplasia, Atrophic gastritis, Gastric premalignant lesion
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.
Interventions
DRUGEflornithine
Eflornithine\*, 2 tablets, Oral, Daily for 18 months
OTHEREflornithine placebo
Eflornithine placebo, 2 tablets, Oral, Daily for 18 months
Sponsors
National Cancer Institute (NCI)
Cancer Prevention Pharmaceuticals, Inc.
Vanderbilt-Ingram Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 69 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Difference in Cell DNA Damage, Based on Percent Positive Cells, Between Patients Treated With DFMO and Patients Treated With Placebo at 6 Months. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | at 18 and 24 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. | 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. | 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). |
Countries
Honduras, Puerto Rico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eflornithine Eflornithine: Eflornithine\*, 2 tablets, Oral, Daily for 18 months | 45 |
| Eflornithine Placebo Eflornithine placebo: Eflornithine placebo, 2 tablets, Oral, Daily for 18 months | 46 |
| Total | 91 |
Baseline characteristics
| Characteristic | Eflornithine | Eflornithine Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 45 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 46 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 45 Participants | 46 Participants | 91 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Honduras | 43 participants | 43 participants | 86 participants |
| Region of Enrollment Puerto Rico | 2 participants | 3 participants | 5 participants |
| Sex: Female, Male Female | 34 Participants | 33 Participants | 67 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 46 |
| other Total, other adverse events | 2 / 45 | 3 / 46 |
| serious Total, serious adverse events | 2 / 45 | 2 / 46 |
Outcome results
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.
Time frame: at 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eflornithine | The Difference in Cell DNA Damage, Based on Percent Positive Cells, Between Patients Treated With DFMO and Patients Treated With Placebo at 6 Months. | 5.07 Percentage of positive cells | Standard Deviation 21.05 |
| Eflornithine Placebo | The Difference in Cell DNA Damage, Based on Percent Positive Cells, Between Patients Treated With DFMO and Patients Treated With Placebo at 6 Months. | 7.32 Percentage of positive cells | Standard Deviation 21.6 |
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).
Time frame: at 6, 18, and 24 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.
Time frame: 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.
Time frame: at 6, 18 and 24 months