Clinical trial NCT01363232: Safety, Pharmacokinetics and Pharmacodynamics of BKM120 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 BKM120 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Selected Solid Tumors
Keywords: BKM120
MEK162
RAS RAF mutations
triple negative breast cancer
pancreatic cancer, ovarian cancer
NSCLC progressed on EGFR TKI
PI3K inhibitor
MEK inhibitor
Lead sponsor: Array BioPharma
Sponsor class: INDUSTRY
First posted: 2011-06-01
Enrollment: 89
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 the recommended phase II dose (RP2D) of the orally administered phosphatidylinositol 3'-kinase (PI3K) inhibitor BKM120 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (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 BKM120 and MEK162.

Study drugs will be administered once daily orally on a continuous schedule. 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

Exclusion Criteria:

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

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities
timeFrame: during Cycle 1 of treatment with BKM120 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 BKM120 and MEK162
timeFrame: during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15
measure: Treatment -induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor.
timeFrame: during the first cycle of treatment on Cycle 1 Day 15 and at disease progression
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Mass General 2
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute Study Coordinator
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center MSKCC (2)
state: New York
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas CCC Faris
state: South Carolina
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center MD Anderson PSC
state: Texas
city: Toronto
country: Canada
facility: Pfizer Investigative Site
state: Ontario
city: Essen
country: Germany
facility: Pfizer Investigative Site
city: Heidelberg
country: Germany
facility: Pfizer Investigative Site
city: Utrecht
country: Netherlands
facility: Pfizer Investigative Site
city: Singapore
country: Singapore
facility: Pfizer Investigative Site
city: Barcelona
country: Spain
facility: Pfizer Investigative Site
state: Catalunya
city: Bellinzona
country: Switzerland
facility: Pfizer Investigative Site
Study officials:
affiliation: 1-800-718-1021
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Bardia A, Gounder M, Rodon J, Janku F, Lolkema MP, Stephenson JJ, Bedard PL, Schuler M, Sessa C, LoRusso P, Thomas M, Maacke H, Evans H, Sun Y, Tan DSW. Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. Oncologist. 2020 Jan;25(1):e160-e169. doi: 10.1634/theoncologist.2019-0297. Epub 2019 Aug 8.