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

NCT01859351 | Terminated Phase 1

• 2 other identifiers: WX/90-0012012-004552-11
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Solid Tumours

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

Study Arms (2)

WX-037

EXPERIMENTAL

PI3K inhibitor

Drug: WX-037

WX-037 in combination with WX-554

EXPERIMENTAL

PI3K inhibitor in combination with MEK inhibitor

Drug: WX-037; Drug: WX-554

Interventions

WX-037 DRUG

WX-037; WX-037 in combination with WX-554

WX-554 DRUG

WX-037 in combination with WX-554

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heidelberg Pharma AG: lead

Study Sites (3)

Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Guy's and St Thomas' Foundation Trust, Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Study Officials

• Udai Banerji, MD

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: May 21, 2013
• Study Start: July 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 16, 2014

Record last verified: 2014-05

Locations

GB (3)