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

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumours
• Intervention / Treatment: Drug: WX-037; Drug: WX-554

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SE1 9RT
    • Guy's and St Thomas' Foundation Trust, Guy's Hospital
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden NHS Foundation Trust

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WX-037; PI3K inhibitor	Drug: WX-037
Experimental: WX-037 in combination with WX-554; PI3K inhibitor in combination with MEK inhibitor	Drug: WX-037; Drug: WX-554

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Heidelberg Pharma AG
• Investigators: Principal Investigator: Udai Banerji, MD, Royal Marsden NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: April 23, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (Estimate): May 21, 2013

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/90-001; 2012-004552-11 (EudraCT Number)