Curcumin in Preventing Gastric Cancer in Patients With Chronic Atrophic Gastritis or Gastric Intestinal Metaplasia

Chronic Atrophic Gastritis Clinical Trial

Official title:

Randomized, Double-Blind, Placebo-Controlled Trial of Meriva® (Curcuminoids) as a Candidate Chemoprevention Agent for Gastric Carcinogenesis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02782949
• Other study ID #: NCI-2016-00713
• Secondary ID: NCI-2016-00713N0
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 4, 2017
• Est. completion date: April 1, 2025

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase IIb trial studies how well curcumin works in preventing gastric cancer in patients with chronic atrophic gastritis and/or gastric intestinal metaplasia. Curcumin is an antioxidant compound found in plants that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Description:

PRIMARY OBJECTIVES:

I. To compare the change in gastric mucosal interleukin 1beta (IL-1beta) cytokine level, quantified by Luminex assay technology, after a 6-month intervention in participants randomly assigned to the curcumin (Meriva [curcuminoids]) versus placebo arms.

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of Meriva versus placebo. II. To compare changes in Histology Gastric Score (HGS) from baseline to 6 months for Meriva versus placebo.

III. To compare changes in additional gastric mucosal cytokine/chemokine levels (interleukin 8 [IL-8], tumor necrosis factor-alpha [TNFalpha], and inducible protein 10 [IP-10]; quantified by Luminex assay).

IV. To compare changes in gastric mucosal deoxyribonucleic acid (DNA) damage as assessed by immunohistochemistry (IHC), of the biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHdG) and phosphorylated subtype of histone H2A (H2AX).

V. To explore associations between proinflammatory cytokine genotype status (IL-1beta, IL-8, and TNFalpha single nucleotide polymorphisms [SNPs]; characterized at baseline) and the above outcomes.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM 1: Patients receive curcumin orally (PO) twice daily (BID) for 180 days in the absence of unacceptable toxicity.

ARM 2: Patients receive placebo PO BID for 180 days in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and 7 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: April 1, 2025
• Est. primary completion date: October 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• PRE-REGISTRATION INCLUSION CRITERIA

• Ability to understand and the willingness to sign a written informed consent document

• Willingness to undergo screening tests and procedures

• Willingness to provide blood and tissue samples for safety/toxicity monitoring and biomarker analyses

• Willingness to avoid the use of curcumin or any over-the-counter or prescription medications containing curcumin or curcuminoids

• REGISTRATION/RANDOMIZATION INCLUSION CRITERIA

• Histologically-confirmed chronic multifocal atrophic gastritis (MAG) and/or gastric intestinal metaplasia (GIM)

• Helicobacter pylori negative, defined as negative stool antigen testing and negative histological examination

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1

• Aspartate transaminase (AST), alanine transferase (ALT) within institutional limits of normal or judged to be not clinically significant by the investigator

• Alkaline phosphatase within institutional limits of normal or judged to be not clinically significant by the investigator

• Platelets within institutional limits of normal or judged to be not clinically significant by the investigator

• Hemoglobin within institutional limits of normal or judged to be not clinically significant by the investigator

• White blood cells (WBC) within institutional limits of normal or judged to be not clinically significant by the investigator

• Blood urea nitrogen (BUN) within institutional limits of normal or judged to be not clinically significant by the investigator

• Total bilirubin within institutional limits of normal or judged to be not clinically significant by the investigator

• Creatinine within institutional limits of normal or judged to be not clinically significant by the investigator

• Not pregnant or breast feeding; Note: The effects of Meriva on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, individuals of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

Exclusion Criteria:

• PRE-REGISTRATION EXCLUSION CRITERIA

• History of other malignancy =< 2 years prior to the registration/randomization evaluation, with the exception of basal cell or squamous cell skin cancer

• History of colorectal cancer; exception: individuals with stage I or II colorectal cancer who have not received any chemotherapy

• Known diagnosis of human immunodeficiency virus (HIV); Note: An HIV screening test does not have to be performed to evaluate this criterion

• History of gastric surgery

• Receiving any other investigational agents

• Use of any anticoagulation medications, such as warfarin or Coumadin

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant or breast feeding; Note: Pregnant women are excluded from this study; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Meriva, breastfeeding should be discontinued if the mother is treated with Meriva

• REGISTRATION/RANDOMIZATION EXCLUSION CRITERIA

• Receiving any other investigational, anticoagulation, and/or chemotherapy agents

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Meriva

Related Conditions & MeSH terms

• Atrophy
• Chronic Atrophic Gastritis
• Gastritis
• Gastritis, Atrophic

Intervention

Drug:
• Curcumin
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Placebo Administration
Given PO
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
Honduras	Hospital Regional de Occidente	Santa Rosa De Copan
Puerto Rico	University of Puerto Rico	San Juan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

Honduras,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proinflammatory Cytokine Genotype Status (IL-1beta, IL-8, and TNFalpha Single Nucleotide Polymorphisms)	Will be examined in relation to the outcomes above to further characterize the at-risk population and generate hypotheses for future studies.	At baseline
Primary	Absolute Change in IL-1beta Cytokine Levels in the Gastric Mucosa	Will be measured by Luminex assay. If the data are not normally distributed, the Wilcoxon Rank-Sum test will be used. The 95% confidence intervals will also be provided.	Baseline up to 6 months
Secondary	Change in Histology Gastric Score	Will compare changes in histology gastric score for curcumin versus placebo.; Correa Histopathology Scoring System values according to the histological diagnosis categories Histological diagnosis Correa Histopathology Scores (range); Normal 1; non-atrophic gastritis(NAG) 2; multifocal atrophic gastritis without intestinal metaplasia (MAG) 3.25-4.00*; IM (intestinal metaplasia) 4.30-5.00*; Dysplasia 5.25-5.75*; Gastric Cancer 6	Baseline up to 6 months
Secondary	Additional Gastric Mucosal Cytokine/Chemokine Levels (TNFalpha, and IP-10)	Will be quantified with Luminex assay. Changes in the concentrations (or categories) will be explored within and between the intervention arms. Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups. McNemar's tests, Wilcoxon signed rank tests, and paired sample t-tests will be used to assess differences within each arm. Graphical methods (i.e. boxplots, scatter plots, etc.) will also be used to describe the data.	Baseline up to 6 months
Secondary	Gastric Mucosal Deoxyribonucleic Acid (DNA) Damage	Will be assessed by immunohistochemistry. Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups. McNemar's tests, Wilcoxon signed rank tests, and paired sample t-tests will be used to assess differences within each arm. Graphical methods (i.e. boxplots, scatter plots, etc.) will also be used to describe the data.	Baseline up to 6 months