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

Advanced Solid Tumours Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01581060
• Other study ID #: WX/80-003
• Secondary ID: 2011-003408-19
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: March 28, 2012
• Last updated: May 15, 2014
• Start date: March 2012
• Est. completion date: April 2014

Study information

• Verified date: May 2014
• Source: Wilex
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Tumours

Intervention

Drug:
• WX-554
Capsules of WX-554

Locations

Country	Name	City	State
United Kingdom	Queen's University Belfast Cancer Centre	Belfast
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	St James' Institute of Oncology	Leeds
United Kingdom	Christie NHS Foundation Trust, Oak Road Treatment Centre	Manchester
United Kingdom	Sir Bobby Robson Cancer Trials Research Centre	Newcastle Upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
Wilex

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Primary	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)	Yes
Primary	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	Yes
Secondary	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	No
Secondary	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	Yes
Secondary	Tumour response evaluation using RECIST 1.1		expected average of 3-6 months	No