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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01581060
Recruitment Status : Terminated (Study terminated for business reasons)
First Posted : April 19, 2012
Last Update Posted : May 16, 2014
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumours Drug: WX-554 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : March 2012
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Arm Intervention/treatment
Experimental: WX-554 Drug: WX-554
Capsules of WX-554

Primary Outcome Measures :
  1. 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. [ Time Frame: Cycle 1 (21 days) ]
  2. 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 [ Time Frame: Cycle 1 (21 days) ]
  3. 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. [ Time Frame: expected average of 3-6 months ]

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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01581060

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

Responsible Party: Wilex Identifier: NCT01581060     History of Changes
Other Study ID Numbers: WX/80-003
2011-003408-19 ( EudraCT Number )
First Posted: April 19, 2012    Key Record Dates
Last Update Posted: May 16, 2014
Last Verified: May 2014