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

Phase 1

Completed

• Conditions: Solid Tumor; Unspecified Adult Solid Tumor, Protocol Specific
• Interventions: Drug: BEZ235 + MEK162

• Registration Number: NCT01337765
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-04-02
• Study First Submitted QC: 2011-04-15
• Study First Posted: 2011-04-19
• Study Start: 2011-07-08
• Primary Completion: 2013-03-22
• Study Completion: 2013-03-22
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-07
• Last Update Posted: 2020-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BEZ235 + MEK162	BEZ235 + MEK162	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Overall response rate, duration of response, time to response and progression free survival	every 8 weeks of treatment
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
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

Trial Locations

Locations (3)

Massachusetts General Hospital Mass General 2; 🇺🇸 Boston, Massachusetts, United States

University of Texas/MD Anderson Cancer Center MD Anderson PSC; 🇺🇸 Houston, Texas, United States

Pfizer Investigative Site; 🇪🇸 Barcelona, Cataluña, Spain