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

Phase 1

Terminated

• Conditions: Advanced Solid Tumours
• Interventions: Drug: WX-554

• Registration Number: NCT01581060
• Lead Sponsor: Heidelberg Pharma AG

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03
• Study First Submitted: 2012-03-28
• Study First Submitted QC: 2012-04-18
• Study First Posted: 2012-04-19
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-15
• Last Update Posted: 2014-05-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

1. Patients with advanced, metastatic and/or progressive solid tumours for whom there is no effective standard therapy available.
2. Evaluable or measurable disease
3. Has normal organ functions; is no greater than 2 on the ECOG Performance Scale
4. life expectancy of >3 months
5. negative hCG test in women of childbearing potential

Exclusion Criteria

1. Patients who received an investigational anti-cancer drug within 4 weeks of starting the study
2. Patients who received major surgery, radiotherapy, or immunotherapy within 4 weeks of starting the study
3. Clinically significant, unresolved toxicity from previous anti-cancer therapy Patients
4. Patients who previously received a MEK inhibitor
5. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
6. Known medical history of retinal vein occlusion, intraocular pressure greater than 21 mm Hg or patient considered at risk of retinal vein thrombosis.
7. Known HIV positivity or active hepatitis B or C infection.
8. History of clinically significant cardiac condition

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
WX-554	WX-554	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (5)

St James' Institute of Oncology; 🇬🇧 Leeds, United Kingdom

Sir Bobby Robson Cancer Trials Research Centre; 🇬🇧 Newcastle Upon Tyne, United Kingdom

Queen's University Belfast Cancer Centre; 🇬🇧 Belfast, United Kingdom

Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

Christie NHS Foundation Trust, Oak Road Treatment Centre; 🇬🇧 Manchester, United Kingdom