Advanced Solid Tumors, Selected Solid Tumors
Conditions
Keywords
BKM120, MEK162, RAS RAF mutations, triple negative breast cancer, pancreatic cancer, ovarian cancer, NSCLC progressed on EGFR TKI, PI3K inhibitor, MEK inhibitor
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.
Interventions
DRUGBKM120 + MEK162
Sponsors
Array Biopharma, now a wholly owned subsidiary of Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose Limiting Toxicities | during Cycle 1 of treatment with BKM120 and MEK162 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Canada, Germany, Netherlands, Singapore, Spain, Switzerland, United States
Outcome results
None listed