Clinical trial NCT01337765: Safety, Pharmacokinetics and Pharmacodynamics of BEZ235 Plus MEK162 in Selected Advanced Solid Tumor Patients
Official title: A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BEZ235 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Solid Tumor
Keywords: BEZ235,
MEK162
RAS RAF mutations,
triple negative breast cancer
pancreatic cancer,
NSCLC progressed on EGFR TKI
PI3K/mTOR inhibitor,
MEK inhibitor
Advanced and selected solid tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-04-19
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or RP2D of the orally administered PI3K/mTOR inhibitor BEZ235 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with EGFR mutant NSCLC which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BEZ235 and MEK162.

Study drugs will be administered orally on a continuous schedule, MEK162 bid and BEZ235 qd, a treatment cycle is defined as 28 days.


Eligibility criteria: Inclusion Criteria:

* histologically/cytologically confirmed, advanced non resectable solid tumors
* Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0

Exclusion Criteria:

* Patients with primary CNS tumor or CNS tumor involvement
* Diabetes mellitus - Unacceptable ocular/retinal conditions

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities
timeFrame: during Cycle 1 of treatment with BEZ235 and MEK162
Secondary outcomes:
measure: Number of participants with adverse events and serious adverse events
timeFrame: from Cycle 1 Day 1 until treatment discontinuation
measure: Overall response rate, duration of response, time to response and progression free survival
timeFrame: every 8 weeks of treatment
measure: Time versus plasma concentration profiles of BEZ235 and MEK162
timeFrame: during the first cycle of treatment
measure: Treatment-induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor
timeFrame: during the first cycle of treatment and at disease progression
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Mass General 2
state: Massachusetts
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center MD Anderson PSC
state: Texas
city: Parkville
country: Australia
facility: Pfizer Investigative Site
state: Victoria
city: Toronto
country: Canada
facility: Pfizer Investigative Site
state: Ontario
city: Villejuif Cedex
country: France
facility: Pfizer Investigative Site
city: Barcelona
country: Spain
facility: Pfizer Investigative Site
state: Cataluña
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: