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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01337765

Collaborator

(none)

Enrollment

Locations

Arm

20.5

Actual Duration (Months)

4.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Unspecified Adult Solid Tumor, Protocol Specific Solid Tumor	Drug: BEZ235 + MEK162	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 8, 2011

Actual Primary Completion Date :

Mar 22, 2013

Actual Study Completion Date :

Mar 22, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BEZ235 + MEK162	Drug: BEZ235 + MEK162

Arm

Intervention/Treatment

Experimental: BEZ235 + MEK162

Drug: BEZ235 + MEK162

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital Mass General 2	Boston	Massachusetts	United States	02114
2	University of Texas/MD Anderson Cancer Center MD Anderson PSC	Houston	Texas	United States	77030-4009
3	Pfizer Investigative Site	Parkville	Victoria	Australia	3050
4	Pfizer Investigative Site	Toronto	Ontario	Canada	M5G 2M9
5	Pfizer Investigative Site	Villejuif Cedex		France	94805
6	Pfizer Investigative Site	Barcelona	Cataluña	Spain	08035