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

• Status: Completed
• Trial end date: 2014-11-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Trametinib

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.