Safety, Pharmacokinetics and Pharmacodynamics of BEZ235 Plus MEK162 in Selected Advanced Solid Tumor Patients

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BEZ235 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors

Conditions
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Solid Tumor, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: BEZ235 + MEK162


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEZ235 + MEK162<br> | Drug: BEZ235 + MEK162<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Limiting Toxicities | A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination | during Cycle 1 of treatment with BEZ235 and MEK162 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events and serious adverse events | A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination | 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 BEZ235 and MEK162 | A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination | during the first cycle of treatment | 
| Treatment-induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor | A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination | during the first cycle of treatment and at disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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