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

Phase 1

Terminated

• Conditions: Advanced Solid Tumours
• Interventions: Drug: WX-037; Drug: WX-554

• Registration Number: NCT01859351
• Lead Sponsor: Heidelberg Pharma AG

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-04-23
• Study First Submitted QC: 2013-05-17
• Study First Posted: 2013-05-21
• Study Start: 2013-07
• 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: 13

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
WX-037	WX-037	PI3K inhibitor
WX-037 in combination with WX-554	WX-554	PI3K inhibitor in combination with MEK inhibitor
WX-037 in combination with WX-554	WX-037	PI3K inhibitor in combination with MEK inhibitor

Primary Outcome Measures

Name	Time	Method
Incidence of Dose limiting toxicities	during cycle 1 (21days) of treatment with WX-037
Incidence of Dose Limiting toxicities	during cycle 1 (21 days) of treatment with WX-037 and WX-554

Secondary Outcome Measures

Name	Time	Method
Number of patients with adverse Events and serious adverse events	from cycle 1 day 1 until treatment discontinuation, an estimated average of 18 weeks
Assessment of PK variables, peak plasma concentration (Cmax), area under the curve (AUC)	two PK profiles in cycle 1
Determination of PD markers; changes from baseline in biomarkers of pathway inhibition	predose until treatment discontinuation, an estimated average of 18 weeks

Trial Locations

Locations (3)

Royal Marsden NHS Foundation Trust; 🇬🇧 Sutton, Surrey, United Kingdom

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

Guy's and St Thomas' Foundation Trust, Guy's Hospital; 🇬🇧 London, United Kingdom