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A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 in Selected Advanced Solid Tumor Patients

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01155453
First Posted: July 1, 2010
Last Update Posted: June 21, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose

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 Intervention Phase
Advanced and Selected Solid Tumors Drug: BKM120 Drug: GSK1120212 Phase 1

Study Type: Interventional
Study Design: 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.

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212 [ Time Frame: in average 1 year ]

Secondary Outcome Measures:
  • 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) ]

Enrollment: 113
Study Start Date: April 2010
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BKM120 + GSK1120212 DE
Dose Escalation
Drug: BKM120 Drug: GSK1120212
Experimental: BKM120 + GSK1120212 NSCLC patients
Advanced RAS or BRAF mutant NSCLC patients
Drug: BKM120 Drug: GSK1120212
Experimental: BKM120 + GSK1120212 ovarian cancer patients
Advanced RAS or BRAF mutant ovarian cancer patients
Drug: BKM120 Drug: GSK1120212
Experimental: BKM120 + GSK1120212 pancreatic cancer patients
Advanced RAS or BRAF mutant pancreatic cancer patients
Drug: BKM120 Drug: GSK1120212

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

  Contacts and Locations
Information from the National Library of Medicine

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


Locations
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
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01155453     History of Changes
Other Study ID Numbers: CBKM120B2101
2009-017157-35 ( EudraCT Number )
First Submitted: June 17, 2010
First Posted: July 1, 2010
Last Update Posted: June 21, 2016
Last Verified: June 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
BKM120
RAS RAF mutations,
triple negative breast cancer,
pancreatic cancer,
PI3K inhibitor,
MEK inhibitor

Additional relevant MeSH terms:
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action