A Phase I Study of Oral MEK162 in Japanese Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
In this study, MEK162 will be administered to Japanese patients with advanced solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. The trial will investigate the safety and tolerability and determine the MTD of MEK162 in Japanese patients.

Official Title
-----------------
A Phase I Study of Oral MEK162 in Japanese Patients With Advanced Solid Tumors

Conditions
-----------------
Advanced Solid Tumor

Intervention / Treatment
-----------------
* Drug: MEK162


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with histologically-confirmed, advanced unresectable solid tumors who have progressed within three months before screening/baseline visit. Availability of a representative formalin fixed paraffin embedded tumor tissue sample. At least one measurable or non-measurable lesion Age ≥ 18 years Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 Good organ (hepatic, kidney, BM) function at screening/baseline visit. Exclusion Criteria: Brain metastasis unless treated and free of signs/symptoms attributable to brain metastasis in the absence of corticosteroid therapy and anti-epileptic therapy. Impaired cardiac function or clinically significant cardiac disease incl. unstable angina pectoris ≤ 3 months prior to starting study drug and Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug. Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEK162<br>MEK162 will be administered orally once on Day 1 of Cycle 1 and continuously on a BID schedule, starting on Day 2 of Cycle 1 and on Day 1 of subsequent cycles. Each cycle will be 28 days in duration. Dose will be escalated and starting dose is 30 mg. Any doses that are missed should be skipped and should not be replaced or made up during the evening dosing or on a subsequent day, whichever applies. The prescribed BID doses should be taken 12 ± 2 hrs apart. | Drug: MEK162<br>* MEK162 in an oral formulation. It is a film-coated capsule-shape tablets (i.e. caplets).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose limiting toxicities | Incidence of frequency of Dose limiting toxicities during first 4 weeks will be measured according to the commen terminology criteria for adverse events (CTCAE). | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events and serious adverse events, changes in laboratory values | Incidence and severity of adverse events and serious adverse events, changes in laboratory values will be measured during the treatment. | 4 months | 
| Plasma concentration of MEK162 and AR00426032active metabolite of MEK162 and derived PK parameters of MEK162 and the active metabolite. | Plasma concentration of MEK162 and active metabolite of MEK162 and derived PK parameters of MEK162 and the active metabolite will be measured with serial plasma samples during treatment for first 2 months. | 2 months | 
| Tumor responses according to RECIST 1.1 | Tumor responses will be measured according to RECIST 1.1 | 4 months | 
| Levels of p-ERK in tumor and skin | Levels of p-ERK in tumor during treatment and skin for first 2 weeks will be measured. | 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MEK, Advanced solid tumor