Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 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:
NCT01363232
First received: May 24, 2011
Last updated: December 19, 2013
Last verified: December 2013

May 24, 2011
December 19, 2013
August 2011
April 2014   (final data collection date for primary outcome measure)
Incidence of Dose Limiting Toxicities [ Time Frame: during Cycle 1 of treatment with BKM120 and MEK162 ] [ Designated as safety issue: Yes ]
Incidence of Dose Limiting Toxicities [ Time Frame: during Cycle 1 of treatment with BEZ235 and MEK162 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01363232 on ClinicalTrials.gov Archive Site
  • Number of participants with adverse events and serious adverse events. [ Time Frame: from Cycle 1 Day 1 until treatment discontinuation ] [ Designated as safety issue: Yes ]
  • Overall response rate, duration of response, time to response and progression free survival [ Time Frame: every 8 weeks of treatment ] [ Designated as safety issue: No ]
  • Time versus plasma concentration profiles of BKM120 and MEK162 [ Time Frame: during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15 ] [ Designated as safety issue: No ]
  • Treatment -induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor. [ Time Frame: during the first cycle of treatment on Cycle 1 Day 15 and at disease progression ] [ Designated as safety issue: No ]
  • Number of participants with adverse events and serious adverse events. [ Time Frame: from Cycle 1 Day 1 until treatment discontinuation ] [ Designated as safety issue: Yes ]
  • Overall response rate, duration of response, time to response and progression free survival [ Time Frame: every 8 weeks of treatment ] [ Designated as safety issue: No ]
  • Time versus plasma concentration profiles of BEZ235 and MEK162 [ Time Frame: during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15 ] [ Designated as safety issue: No ]
  • Treatment -induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor and skin [ Time Frame: during the first cycle of treatment on Cycle 1 Day 15 and at disease progression ] [ 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 their potential relationship to clinical responses. [ Time Frame: at baseline (pre-treatment) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 in Selected Advanced Solid Tumor Patients
A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BKM120 Plus MEK162 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 the recommended phase II dose (RP2D) of the orally administered phosphatidylinositol 3'-kinase (PI3K) inhibitor BKM120 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BKM120 and MEK162.

Study drugs will be administered once daily orally on a continuous schedule. A treatment cycle is defined as 28 days.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Advanced Solid Tumors,
  • Selected Solid Tumors
Drug: BKM120 + MEK162
Experimental: BKM120 + MEK162
Intervention: Drug: BKM120 + MEK162
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
86
April 2014
April 2014   (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

Exclusion Criteria:

  • Patients with primary CNS tumor or CNS tumor involvement.
  • 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,   Germany,   Canada,   Switzerland,   Netherlands,   Singapore,   Spain
 
NCT01363232
CMEK162X2101, 2011-001083-22
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
December 2013

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