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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01155453
First received: June 17, 2010
Last updated: June 4, 2013
Last verified: June 2013

June 17, 2010
June 4, 2013
April 2010
July 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01155453 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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.

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
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Advanced and Selected Solid Tumors
  • Drug: BKM120
  • Drug: GSK1120212
  • Experimental: BKM120 + GSK1120212 DE
    Dose Escalation
    Interventions:
    • Drug: BKM120
    • Drug: GSK1120212
  • Experimental: BKM120 + GSK1120212 NSCLC patients
    Advanced RAS or BRAF mutant NSCLC patients
    Interventions:
    • Drug: BKM120
    • Drug: GSK1120212
  • Experimental: BKM120 + GSK1120212 ovarian cancer patients
    Advanced RAS or BRAF mutant ovarian cancer patients
    Interventions:
    • Drug: BKM120
    • Drug: GSK1120212
  • Experimental: BKM120 + GSK1120212 pancreatic cancer patients
    Advanced RAS or BRAF mutant pancreatic cancer patients
    Interventions:
    • Drug: BKM120
    • Drug: GSK1120212
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
108
July 2013
July 2013   (final data collection date for primary outcome measure)

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.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Canada,   Spain,   Switzerland
 
NCT01155453
CBKM120B2101, 2009-017157-35
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP