Solid Tumor, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
BEZ235,, MEK162, RAS RAF mutations,, triple negative breast cancer, pancreatic cancer,, NSCLC progressed on EGFR TKI, PI3K/mTOR inhibitor,, MEK inhibitor, Advanced and selected solid tumors
Brief summary
This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or RP2D of the orally administered PI3K/mTOR inhibitor BEZ235 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with EGFR mutant 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 BEZ235 and MEK162. Study drugs will be administered orally on a continuous schedule, MEK162 bid and BEZ235 qd, a treatment cycle is defined as 28 days.
Interventions
DRUGBEZ235 + MEK162
Sponsors
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 1.0
Exclusion criteria
* Patients with primary CNS tumor or CNS tumor involvement * Diabetes mellitus - Unacceptable ocular/retinal conditions Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting Toxicities | during Cycle 1 of treatment with BEZ235 and MEK162 | A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events and serious adverse events | from Cycle 1 Day 1 until treatment discontinuation | A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination |
| Overall response rate, duration of response, time to response and progression free survival | every 8 weeks of treatment | — |
| Time versus plasma concentration profiles of BEZ235 and MEK162 | during the first cycle of treatment | A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination |
| Treatment-induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor | during the first cycle of treatment and at disease progression | A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination |
Countries
Australia, Canada, France, Spain, United States
Outcome results
None listed