A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 in Selected Advanced Solid Tumor Patients
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.
2 other identifiers
interventional
113
5 countries
7
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2010
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2010
CompletedFirst Submitted
Initial submission to the registry
June 17, 2010
CompletedFirst Posted
Study publicly available on registry
July 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2014
CompletedDecember 9, 2020
June 1, 2016
4.6 years
June 17, 2010
December 6, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212
in average 1 year
Secondary Outcomes (5)
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
in average 1 year
Determine the single and multiple dose pharmacokinetics of BKM120 and GSK1120212 in measurement of the plasma concentration profiles of BKM120 and GSK1120212
Assessed during the first Cycle (28 days) of treatment
Preliminary anti-tumor activity of the combination
Assessed every 8 weeks of treatment
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
Assessed every 2 weeks during the first cycle, then every 4 weeks
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
Assessed at baseline (pre-treatment)
Study Arms (4)
BKM120 + GSK1120212 DE
EXPERIMENTALDose Escalation
BKM120 + GSK1120212 NSCLC patients
EXPERIMENTALAdvanced RAS or BRAF mutant NSCLC patients
BKM120 + GSK1120212 ovarian cancer patients
EXPERIMENTALAdvanced RAS or BRAF mutant ovarian cancer patients
BKM120 + GSK1120212 pancreatic cancer patients
EXPERIMENTALAdvanced RAS or BRAF mutant pancreatic cancer patients
Interventions
Eligibility Criteria
You may qualify if:
- histologically/ cytologically confirmed, advanced non resectable solid tumors
- Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0
You may not qualify if:
- Patients with primary Central Nervous System (CNS) tumor or CNS tumor involvement.
- Clinically manifested diabetes mellitus - Unacceptable ocular/retinal conditions
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
University of California at Los Angeles Div. of Hematology/Oncology
Los Angeles, California, 90095, United States
University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)
Houston, Texas, 77030-4009, United States
Novartis Investigative Site
Leuven, 3000, Belgium
Novartis Investigative Site
Toronto, Ontario, M5G 2M9, Canada
Novartis Investigative Site
Seville, Andalusia, 41013, Spain
Novartis Investigative Site
Barcelona, Catalonia, 08035, Spain
Novartis Investigative Site
Bellinzona, 6500, Switzerland
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 17, 2010
First Posted
July 1, 2010
Study Start
April 1, 2010
Primary Completion
November 1, 2014
Study Completion
November 1, 2014
Last Updated
December 9, 2020
Record last verified: 2016-06