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

Phase 2

Active, not recruiting

Conditions: Chronic Atrophic Gastritis
Gastric Carcinoma

Interventions: Drug: Curcumin
Other: Laboratory Biomarker Analysis
Other: Placebo Administration
Other: Quality-of-Life Assessment

Registration Number: NCT02782949

Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Detailed 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 & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 50

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (curcumin)	Laboratory Biomarker Analysis	Patients receive curcumin PO BID for 180 days in the absence of unacceptable toxicity.
Arm I (curcumin)	Curcumin	Patients receive curcumin PO BID for 180 days in the absence of unacceptable toxicity.
Arm I (curcumin)	Quality-of-Life Assessment	Patients receive curcumin PO BID for 180 days in the absence of unacceptable toxicity.
Arm II (placebo)	Placebo Administration	Patients receive placebo PO BID for 180 days in the absence of unacceptable toxicity.
Arm II (placebo)	Laboratory Biomarker Analysis	Patients receive placebo PO BID for 180 days in the absence of unacceptable toxicity.
Arm II (placebo)	Quality-of-Life Assessment	Patients receive placebo PO BID for 180 days in the absence of unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Absolute Change in IL-1beta Cytokine Levels in the Gastric Mucosa	Baseline up to 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Additional Gastric Mucosal Cytokine/Chemokine Levels (TNFalpha, and IP-10)	Baseline up to 6 months	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.
Gastric Mucosal Deoxyribonucleic Acid (DNA) Damage	Baseline up to 6 months	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.
Change in Histology Gastric Score	Baseline up to 6 months	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) 1. Normal 1 2. non-atrophic gastritis(NAG) 2 3. multifocal atrophic gastritis without intestinal metaplasia (MAG) 3.25-4.00\* 4. IM (intestinal metaplasia) 4.30-5.00\* 5. Dysplasia 5.25-5.75\* 6. Gastric Cancer 6