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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 89
- Locations
- 6
- Primary Endpoint
- Incidence of Dose Limiting Toxicities
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
BKM120 + MEK162
Intervention: BKM120 + MEK162 (Drug)
Outcomes
Primary Outcomes
Incidence of Dose Limiting Toxicities
Time Frame: during Cycle 1 of treatment with BKM120 and MEK162
Secondary Outcomes
- Number of participants with adverse events and serious adverse events.(from Cycle 1 Day 1 until treatment discontinuation)
- Overall response rate, duration of response, time to response and progression free survival(every 8 weeks of treatment)
- Time versus plasma concentration profiles of BKM120 and MEK162(during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15)
- Treatment -induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor.(during the first cycle of treatment on Cycle 1 Day 15 and at disease progression)