Reversal of Preneoplastic Metaplasia in the Stomach With MEK Inhibitor

Gastric Cancer Clinical Trial

Official title:

Reversal of Preneoplastic Metaplasia in the Stomach With MEK Inhibitor Treatment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04454476
• Other study ID #: VICC GI 2049
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 9, 2022
• Est. completion date: May 2025

Study information

• Verified date: September 2023
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: May 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Gastric Cancer
• Initial-onset Gastric Cancer
• Metaplasia
• Stage I Gastric Cancer
• Stomach Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Japan	Nagasaki University Hospital	Nagasaki
Japan	Nihon University School of Medicine	Tokyo
Japan	University of Tokyo Medical Center	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Safety of Trametinib treatment: adverse events	Assessment of side effects induced during or after treatment with Trametinib.	About 12 weeks