Clinical trial NCT01859351: Phase I Study of WX-037 Alone and in Combination With WX-554 in Solid Tumours
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumours
Lead sponsor: Heidelberg Pharma AG
Sponsor class: INDUSTRY
First posted: 2013-05-21
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Dose limiting toxicities
timeFrame: during cycle 1 (21days) of treatment with WX-037
measure: Incidence of Dose Limiting toxicities
timeFrame: during cycle 1 (21 days) of treatment with WX-037 and WX-554
Secondary outcomes:
measure: Number of patients with adverse Events and serious adverse events
timeFrame: from cycle 1 day 1 until treatment discontinuation, an estimated average of 18 weeks
measure: Assessment of PK variables, peak plasma concentration (Cmax), area under the curve (AUC)
timeFrame: two PK profiles in cycle 1
measure: Determination of PD markers; changes from baseline in biomarkers of pathway inhibition
timeFrame: predose until treatment discontinuation, an estimated average of 18 weeks
Other outcomes:
Locations:
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
state: Surrey
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Guy's and St Thomas' Foundation Trust, Guy's Hospital
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Udai Banerji, MD
role: PRINCIPAL_INVESTIGATOR
References: