Phase I Study of WX-037 Alone and in Combination With WX-554 in Solid Tumours

Advanced Solid Tumours Clinical Trial

Official title:

A Phase I Open-label, Dose-escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the PI3K Inhibitor WX-037, Given as a Single Agent and in Combination With the MEK Inhibitor WX-554, in Patients With Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01859351
• Other study ID #: WX/90-001
• Secondary ID: 2012-004552-11
• Status: Terminated
• Phase: Phase 1
• First received: April 23, 2013
• Last updated: May 15, 2014
• Start date: July 2013
• 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 purpose of this study is to test the safety of escalating doses of the novel PI3K inhibitor WX-037 and to explore its effectiveness in combination with WX-554 which targets mitogen activated protein kinase (MEK1 and MEK2). Preclinical evidence indicates that these two novel compounds could provide targeted inhibition of both pathways to block tumour growth.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• 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:

• Patients with advanced, metastatic and/or progressive solid tumors for whom there is no effective standard therapy available (for part 2 in addition patients for whom their PI3K pathway is deregulated)

• Evaluable or measurable disease

• Has normal organ function; is no greater than 2 on the ECOG performance scale

• Negative hCG test in women of childbearing potential

Exclusion Criteria:

• History of diabetes requiring daily medication or history of grade 3 or more fasting hyperglycemia

• Patients with major surgery, radiotherapy, or immunotherapy within 4 weeks of starting the study

• Clinical significant, unresolved toxicity from previous anti-cancer therapy

• Patients who previously received a MEK inhibitor (for combination part only)

• 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 (combination part only)

• Known HIV positivity or active hepatitis B or C infection

• History of clinically significant cardiac condition

Study Design

Allocation: Non-Randomized, 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-037

• WX-554

Locations

Country	Name	City	State
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Guy's and St Thomas' Foundation Trust, Guy's Hospital	London
United Kingdom	Royal Marsden NHS Foundation Trust	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Wilex

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose limiting toxicities		during cycle 1 (21days) of treatment with WX-037	Yes
Primary	Incidence of Dose Limiting toxicities		during cycle 1 (21 days) of treatment with WX-037 and WX-554	Yes
Secondary	Number of patients with adverse Events and serious adverse events		from cycle 1 day 1 until treatment discontinuation, an estimated average of 18 weeks	Yes
Secondary	Assessment of PK variables, peak plasma concentration (Cmax), area under the curve (AUC)		two PK profiles in cycle 1	Yes
Secondary	Determination of PD markers; changes from baseline in biomarkers of pathway inhibition		predose until treatment discontinuation, an estimated average of 18 weeks	Yes