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

Sponsor:	Novartis Pharmaceuticals
Information provided by (Responsible Party):	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01155453

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 + GSK1120212	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: 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:

MedlinePlus related topics: Cancer Ovarian Cancer Pancreatic Cancer

U.S. FDA Resources

Further study details as provided by Novartis:

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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
Preliminary anti-tumor activity of the combination [ Time Frame: Assessed every 8 weeks of treatment ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]

Estimated Enrollment:	105
Study Start Date:	April 2010
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BKM120 + GSK1120212 DE Dose Escalation	Drug: BKM120 + GSK1120212
Experimental: BKM120 + GSK1120212 NSCLC patients Advanced RAS or BRAF mutant NSCLC patients	Drug: BKM120 + GSK1120212
Experimental: BKM120 + GSK1120212 ovarian cancer patients Advanced RAS or BRAF mutant ovarian cancer patients	Drug: BKM120 + GSK1120212
Experimental: BKM120 + GSK1120212 pancreatic cancer patients Advanced RAS or BRAF mutant pancreatic cancer patients	Drug: BKM120 + GSK1120212

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01155453

Contacts

Contact: Novartis Pharmaceuticals

+1(800)340-6843

Locations

United States, California
Novartis Investigative Site	Recruiting
Los Angeles, California, United States, 90095
United States, Texas
Novartis Investigative Site	Recruiting
Houston, Texas, United States, 77030-4009
Belgium
Novartis Investigative Site	Not yet recruiting
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Spain
Novartis Investigative Site	Recruiting
Barcelona, Spain, 08035
Novartis Investigative Site	Not yet recruiting
Sevilla, Spain, 41013
Switzerland
Novartis Investigative Site	Recruiting
Bellinzona, Switzerland, 6500

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01155453 History of Changes
Other Study ID Numbers:	CBKM120B2101, 2009-017157-35
Study First Received:	June 17, 2010
Last Updated:	May 10, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Spain: Ministry of Health Switzerland: Swissmedic

Keywords provided by Novartis:

BKM120
RAS RAF mutations,
triple negative breast cancer,

pancreatic cancer,
PI3K inhibitor,
MEK inhibitor

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on May 24, 2012