A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 in Selected Advanced Solid Tumor Patients
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ClinicalTrials.gov Identifier: NCT01155453 |
Recruitment Status :
Completed
First Posted : July 1, 2010
Last Update Posted : December 9, 2020
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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
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Advanced and Selected Solid Tumors | Drug: BKM120 Drug: GSK1120212 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 113 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 Start Date : | April 2010 |
Actual Primary Completion Date : | November 2014 |
Actual Study Completion Date : | November 2014 |

Arm | Intervention/treatment |
---|---|
Experimental: BKM120 + GSK1120212 DE
Dose Escalation
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Drug: BKM120 Drug: GSK1120212 |
Experimental: BKM120 + GSK1120212 NSCLC patients
Advanced RAS or BRAF mutant NSCLC patients
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Drug: BKM120 Drug: GSK1120212 |
Experimental: BKM120 + GSK1120212 ovarian cancer patients
Advanced RAS or BRAF mutant ovarian cancer patients
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Drug: BKM120 Drug: GSK1120212 |
Experimental: BKM120 + GSK1120212 pancreatic cancer patients
Advanced RAS or BRAF mutant pancreatic cancer patients
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Drug: BKM120 Drug: GSK1120212 |
- Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212 [ Time Frame: in average 1 year ]
- 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 [ Time Frame: 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 [ Time Frame: Assessed during the first Cycle (28 days) of treatment ]
- Preliminary anti-tumor activity of the combination [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Assessed at baseline (pre-treatment) ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01155453
United States, California | |
University of California at Los Angeles Div. of Hematology/Oncology | |
Los Angeles, California, United States, 90095 | |
United States, Texas | |
University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8) | |
Houston, Texas, United States, 77030-4009 | |
Belgium | |
Novartis Investigative Site | |
Leuven, Belgium, 3000 | |
Canada, Ontario | |
Novartis Investigative Site | |
Toronto, Ontario, Canada, M5G 2M9 | |
Spain | |
Novartis Investigative Site | |
Sevilla, Andalucia, Spain, 41013 | |
Novartis Investigative Site | |
Barcelona, Catalunya, Spain, 08035 | |
Switzerland | |
Novartis Investigative Site | |
Bellinzona, Switzerland, 6500 |
Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT01155453 |
Other Study ID Numbers: |
CBKM120B2101 2009-017157-35 ( EudraCT Number ) |
First Posted: | July 1, 2010 Key Record Dates |
Last Update Posted: | December 9, 2020 |
Last Verified: | June 2016 |
BKM120 RAS RAF mutations, triple negative breast cancer, |
pancreatic cancer, PI3K inhibitor, MEK inhibitor |
Neoplasms Trametinib Antineoplastic Agents |
Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |