Clinical trial NCT01155453: A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 in Selected Advanced Solid Tumor Patients
Official title: A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral BKM120 in Combination With Oral GSK1120212 in Adult Patients With Selected Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced and Selected Solid Tumors
Keywords: BKM120
RAS RAF mutations,
triple negative breast cancer,
pancreatic cancer,
PI3K inhibitor,
MEK inhibitor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-07-01
Enrollment: 113
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: This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and /or recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid tumors. The focus will be on tumors with RAS/RAF mutations and on triple negative breast cancer.

Both study drugs will be administered once daily orally on a continuous schedule, a treatment cycle is defined as 28 days.

Cohorts of at least 3 and up to a maximum of 6 patients eligible for the dose-determining set will be enrolled per dose combination below the MTD. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment medically unacceptable, dose-limiting toxicity (DLT) in more than 33% of the treated patients.. At least 12 patients will be required at MTD and 6 patients at RP2D level to allow the evaluation of the combination's safety and pharmacokinetics or pharmacodynamics.

Upon declaration of MTD and/or RP2D, patients will be enrolled to an expansion part of the study, to further assess safety, as well as to learn more about the efficacy of the study drug combination.

* Expansion Arm 1 will consist of approximately 15 patients with RAS or BRAF mutant advanced NSCLC
* Expansion Arm 2 will consist of approximately 15 patients with RAS or BRAF-mutant ovarian cancer
* Expansion Arm 3 will consist of approximately 15 patients with RAS or BRAF-mutant pancreatic cancer


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 Central Nervous System (CNS) tumor or CNS tumor involvement.
* Clinically manifested diabetes mellitus - Unacceptable ocular/retinal conditions

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212
timeFrame: in average 1 year
Secondary outcomes:
measure: Measure the number of Adverse Event and laboratory values that fall outside of pre-determined ranges as a measure of Safety and tolerability of the oral combination of BKM120 and GSK1120212
timeFrame: in average 1 year
measure: Determine the single and multiple dose pharmacokinetics of BKM120 and GSK1120212 in measurement of the plasma concentration profiles of BKM120 and GSK1120212
timeFrame: Assessed during the first Cycle (28 days) of treatment
measure: Preliminary anti-tumor activity of the combination
timeFrame: Assessed every 8 weeks of treatment
measure: Treatment-induced PI3K and MEK/ERK(Mitogen-activated protein kinase /extracellular-signal-regulated kinases) pathway signaling inhibition and evidence of biological activity in tumor and skin
timeFrame: Assessed every 2 weeks during the first cycle, then every 4 weeks
measure: Molecular status (genetic alterations, protein expression and/or activation) of markers related to PI3K and ERK signaling in tumor tissue and blood and investigate their potential relationship to clinical responses
timeFrame: Assessed at baseline (pre-treatment)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles Div. of Hematology/Oncology
state: California
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)
state: Texas
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Bellinzona
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: