Clinical trial NCT01449058: A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
Official title: A Phase Ib Open-label, Multi-center, Dose Escalation and Expansion Study of Orally Administered MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced and Selected Solid Tumors
AML
High Risk and Very High Risk MDS
Keywords: Advanced solid tumor,
AML
high risk and very high risk MDS
dose escalation,
RAS/BRAF mutation,
PI3K inhibitor,
MEK inhibitor,
BYL719,
MEK162
Lead sponsor: Array BioPharma
Sponsor class: INDUSTRY
First posted: 2011-10-07
Enrollment: 139
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 a multi-center, open-label, dose-finding, phase Ib study to estimate the maximum tolerated dose(s) (MTD(s)) and/or recommended dose(s) for expansion (RDE(s)) for the orally administered combination of BYL719 and MEK162. This combination will be explored in adult patients with advanced CRC, esophageal cancer, pancreatic cancer, NSCLC, ovarian cancer, or other advanced solid tumors and in adult patients with AML or high risk and very high risk MDS, with documented RAS or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RDE, four expansion arms will be opened in order to further assess the safety and preliminary activity of the combination of BYL719 and MEK162 in specific patient populations.


Eligibility criteria: Inclusion Criteria:

* Histologically/cytologically confirmed, advanced solid tumors, AML or high risk and very high risk MDS
* Measurable disease as determined by RECIST 1.1

Exclusion Criteria:

* Primary CNS tumor or CNS tumor involvement
* Diabetes mellitus
* Unacceptable ocular/retinal conditions
* Clinically significant cardiac disease or impaired cardiac function

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLT)
timeFrame: during the first cycle (28 days) of treatment with BYL719 and MEK162
Secondary outcomes:
measure: Number of participants with adverse events and serious adverse events
timeFrame: Assessed from Cycle 1 Day 1 until treatment discontinuation
measure: Overall response rate
timeFrame: Assessed every 8 weeks until disease progression
measure: Time to progression
timeFrame: Assessed every 8 weeks until disease progression
measure: Progression free survival
timeFrame: Assessed every 8 weeks until disease progression
measure: Time versus plasma concentration profiles of BYL719 and MEK162
timeFrame: Assessed during the first cycle of treatment
measure: Correlation of baseline mutation or amplification status (PIK3CA, KRAS, NRAS and BRAF) and clinical anti-tumor activity outcome
timeFrame: Assessed at Baseline (pre-treatment)
measure: Clinical benefit rate
timeFrame: Assessed every 4 weeks for 3 months and every 3 months for 6 months followed by every 6 months thereafter until disease progression
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego - Moores Cancer Center Dept Onc
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital CCPO
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Onc. Dept
state: New York
city: The Bronx
country: United States
facility: Montefiore Medical Center SC
state: New York
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center Dept. of Onc.
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Huntsman (3)
state: Utah
city: Parkville
country: Australia
facility: Array BioPharma Investigative Site
state: Victoria
city: Villejuif Cedex
country: France
facility: Array BioPharma Investigative Site
city: Milano
country: Italy
facility: Array BioPharma Investigative Site
state: MI
city: Roma
country: Italy
facility: Array BioPharma Investigative Site
state: RM
city: Barcelona
country: Spain
facility: Array BioPharma Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Array BioPharma Investigative Site
state: Catalunya
city: Bellinzona
country: Switzerland
facility: Array BioPharma Investigative Site
city: Sutton
country: United Kingdom
facility: Array BioPharma Investigative Site
Study officials:
affiliation: 303-381-6604
name: Array BioPharma
role: STUDY_DIRECTOR
References: