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

Advanced and Selected Solid Tumors Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01155453
• Other study ID #: CBKM120B2101
• Secondary ID: 2009-017157-35
• Status: Completed
• Phase: Phase 1
• Start date: April 2010
• Est. completion date: November 2014

Study information

• Verified date: June 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced and Selected Solid Tumors
• Neoplasms

Intervention

Drug:
• BKM120

• GSK1120212

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Toronto	Ontario
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Sevilla	Andalucia
Switzerland	Novartis Investigative Site	Bellinzona
United States	University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)	Houston	Texas
United States	University of California at Los Angeles Div. of Hematology/Oncology	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212		in average 1 year
Secondary	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		in average 1 year
Secondary	Determine the single and multiple dose pharmacokinetics of BKM120 and GSK1120212 in measurement of the plasma concentration profiles of BKM120 and GSK1120212		Assessed during the first Cycle (28 days) of treatment
Secondary	Preliminary anti-tumor activity of the combination		Assessed every 8 weeks of treatment
Secondary	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		Assessed every 2 weeks during the first cycle, then every 4 weeks
Secondary	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		Assessed at baseline (pre-treatment)

External Links

•   Results for CBKM120B2101 on the Novartis Clinical Trial website