Clinical trial NCT04454476: Reversal of Preneoplastic Metaplasia in the Stomach With MEK Inhibitor
Official title: Reversal of Preneoplastic Metaplasia in the Stomach With MEK Inhibitor Treatment
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Gastric Cancer
Metaplasia
Stage I Gastric Cancer
Initial-onset Gastric Cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
First posted: 2020-07-01
Enrollment: 15
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Effectiveness of Trametinib in reversing metaplasia: changes in cell lineages
timeFrame: About 12 months
measure: Safety of Trametinib treatment: adverse events
timeFrame: About 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Tokyo
country: Japan
facility: Nihon University School of Medicine
city: Tokyo
country: Japan
facility: University of Tokyo Medical Center
Study officials:
affiliation: Vanderbilt Medical Center
name: James Goldenring, MD
role: PRINCIPAL_INVESTIGATOR
References: