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

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumours
• Intervention / Treatment: Drug: WX-554

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Queen's University Belfast Cancer Centre
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom, LS9 7TF
    • St James' Institute of Oncology
  • Manchester, United Kingdom, M20 4BX
    • Christie NHS Foundation Trust, Oak Road Treatment Centre
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Sir Bobby Robson Cancer Trials Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WX-554	Drug: WX-554; Capsules of WX-554

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Heidelberg Pharma AG
• Investigators: Principal Investigator: Ruth Plummer, MD, Sir Bobby Robson Cancer Trials Research Centre

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: March 28, 2012
• First Submitted That Met QC Criteria: April 18, 2012
• First Posted (Estimate): April 19, 2012

Study Record Updates

• Last Update Posted (Estimate): May 16, 2014
• Last Update Submitted That Met QC Criteria: May 15, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: WX/80-003; 2011-003408-19 (EudraCT Number)