Phase I/II Dose-escalation Study to Investigate Safety and Pharmacokinetics/ Pharmacodynamics of WX-554 in Patients With Solid Tumours

Study Overview
=================
Brief Summary
-----------------
The aim of part 1 of this study is to determine the optimal biological dose (OBD) and maximum tolerated dose (MTD) for WX-554 and the recommended dose/dose schedules for the chronic treatment in part 2. The aim of part 2 is to further determine the safety and tolerability of chronic treatment with WX-554.

Official Title
-----------------
A Phase I/II, Open-label, Dose-escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor WX-554 in Patients With Solid Tumours

Conditions
-----------------
Advanced Solid Tumours

Intervention / Treatment
-----------------
* Drug: WX-554


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with advanced, metastatic and/or progressive solid tumours for whom there is no effective standard therapy available. Evaluable or measurable disease Has normal organ functions; is no greater than 2 on the ECOG Performance Scale life expectancy of >3 months negative hCG test in women of childbearing potential Exclusion Criteria: Patients who received an investigational anti-cancer drug within 4 weeks of starting the study Patients who received major surgery, radiotherapy, or immunotherapy within 4 weeks of starting the study Clinically significant, unresolved toxicity from previous anti-cancer therapy Patients Patients who previously received a MEK inhibitor Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs. Known medical history of retinal vein occlusion, intraocular pressure greater than 21 mm Hg or patient considered at risk of retinal vein thrombosis. Known HIV positivity or active hepatitis B or C infection. History of clinically significant cardiac condition

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: WX-554<br> | Drug: WX-554<br>* Capsules of WX-554<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Determination of the Optimal Biological Dose (OBD) by the assessment of ERK phosphorylation (pERK) in peripheral blood mononuclear cells (PBMC) and assessment of TNF-alpha in plasma. |  | Cycle 1 (21 days) | 
| Part 1: Determination of the Maximum Tolerated Dose (MTD) for WX-554 by the evaluation of DLTs in 3-6 patients at the end of 1 treatment cycle |  | Cycle 1 (21 days) | 
| Part 2: To further determine the safety and tolerability by evaluating the incidence and severity of adverse events and serious adverse events (as per CTCAE grading), changes in hematology and chemistry values, vital signs, ECGs. |  | expected average of 3-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK variables maximum observed concentration (Cmax), minimum observed concentration (Cmin), time at which Cmax was present (tmax), Area Under Curve (AUC) |  | PK profile on day 1 and day 8 | 
| Assessment of ERK phosphorylation (pERK) in PBMC and tissue, assessment of TNF-alpha in plasma after oral intake of the OBD/MTD. |  | expected average of 3-6 months | 
| Tumour response evaluation using RECIST 1.1 |  | expected average of 3-6 months |