Reversal of Preneoplastic Metaplasia in the Stomach With MEK Inhibitor

Reversal of Preneoplastic Metaplasia in the Stomach With MEK Inhibitor Treatment

This is a study of the safety and effectiveness of Trametinib treatment in patients who have received successful endoscopic submucosal resection of a Stage I gastric cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric Cancer; Metaplasia; Stage I Gastric Cancer; Initial-onset Gastric Cancer
• Intervention / Treatment: Drug: Trametinib treatment; Procedure: Endoscopy

Detailed Description

Objectives:

• To evaluate the efficacy of Trametinib in reversing metaplasia in participants with Stage 1 gastric cancer
• To evaluate the safety of Trametinibin in Stage I gastric cancer patients

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: James Goldenring, MD; Phone Number: 615-936-3726; Email: jim.goldenring@vumc.org

Study Locations

• Japan
  • Nagasaki, Japan
    • Nagasaki University Hospital
  • Tokyo, Japan
    • Nihon University School of Medicine
    • Contact: Takuji Gotoda; Email: takujigotoda@yahoo.com.jp
    • Principal Investigator: Takuji Gotoda
  • Tokyo, Japan
    • University of Tokyo Medical Center
    • Contact: Sachiyo Nomura; Email: snomura-gi@umin.ac.jp
    • Principal Investigator: Sachiyo Nomura

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Primary registration

• Person having intact stomach after treatment of early gastric cancer or gastric adenoma
• Person whose treated gastric cancer histological type is intestinal type.
• Person whose treated gastric cancer or gastric adenoma was curatively resected.
• Person who does not have symptoms of gastric cancer recurrence.
• Person who can declare agreement for enrollment by understanding the study and signing the informed consent document after hearing the explanation.
• Person who can visit the hospital in accordance with the schedule.

Secondary registration

• Person who has gastric atrophy at endoscopy.
• Person who does not have symptoms of gastric cancer recurrence by endoscopy.
• Person who has intestinal metaplasia in stomach, histologically confirmed in biopsy specimens taken under endoscopy within 8 weeks prior to taking MEK inhibitor, Trametinib.

Exclusion Criteria:

• Person whose treated gastric cancer was diffuse or signet ring cancer.
• Person whose treated gastric cancer or gastric adenoma was not curatively resected.
• Person who has the history of other malignant disease.
• Person who had a significant improvement in metaplasia after eradication therapy for Helicobacter pylori within one year.
• Person who had plan of eradication Helicobacter pylori in 1 year 9 months
• Person who has history of previous Trametinib or other MEK inhibitor use.
• Person who has history of hypersensitivity to excipients.
• Person who entered clinical trial and took investigational new drug within 12 weeks.
• Presence of active infection other than chronic gastritis.

• Cardiac conditions as follows:

  • Uncontrolled hypertension (BP>=150/95 mm Hg despite medical therapy)
  • Acute myocardial infection within 6 months prior to starting treatment
  • Uncontrolled Angina (Canadian Cardiovascular Society grade II-IV even after medication)
  • Symptomatic heart failure NYHA Class II-IV
  • <45% in the past
  • Severe valvular disease
  • <55% at present
  • Atrial fibrilation in ECG with BPM=>100 Laboratory values as listed below (SI units) Absolute Neutrophil Count <1.5x10A9/L (1500 per mm3) Platelets <100x10A9/L (100,000 per mm3) Hemoglobin<=9.0 g /dL Serum creatinine >1.5 X upper limit of normal (ULN) Serum bilirubin >1.5 x ULN AST or ALT > 2.5 x ULN

Ophthalmological conditions as follows:

Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma (irrespective of IOP)

Male or female patients of reproductive potential and, as judged by the investigator, are not employing an effective method of birth control and pregnant female.

Breast feeding female Have refractory nausea and vomiting , chronic gastrointestinal diseases (e.g . inflammatory bowel disease), or significant bowel resection that would adversely affect the absorption / bioavailability of the orally administered study medication.

Person who has history of hyperrefractory for Trametinib methyl sulfoxide Person who has pneumonia under chest X-ray. Have evidence of any other significant clinical disorder or laboratory finding that, as judgedby the investigator, makes it undesirable for the patient to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trametinib treatment	Drug: Trametinib treatment; 1 mg taken by mouth once a day for 14 days; Procedure: Endoscopy; A tiny camera on the end of a long, flexible tube will be used to examine the stomach and take biopsies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of Trametinib in reversing metaplasia: changes in cell lineages	The ability of Trametinib treatment to decrease the presence of metaplastic cell lineages in biopsies of the lining of the stomach, while also allowing the return of normal cell lineages (i.e. acid-secreting parietal cells). Cell lineages will be identified by immunostaining of tissue sections from biopsies.	About 12 months
Safety of Trametinib treatment: adverse events	Assessment of side effects induced during or after treatment with Trametinib.	About 12 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: James Goldenring, MD, Vanderbilt Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Metaplasia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Trametinib
• Other Study ID Numbers: VICC GI 2049

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes