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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01337765
• Other study ID #: CMEK162X2103
• Secondary ID: 2011-000421-74C4
• Status: Completed
• Phase: Phase 1
• Start date: July 8, 2011
• Est. completion date: March 22, 2013

Study information

• Verified date: October 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: March 22, 2013
• Est. primary completion date: March 22, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• BEZ235 + MEK162

Locations

Country	Name	City	State
Australia	Pfizer Investigative Site	Parkville	Victoria
Canada	Pfizer Investigative Site	Toronto	Ontario
France	Pfizer Investigative Site	Villejuif Cedex
Spain	Pfizer Investigative Site	Barcelona	Cataluña
United States	Massachusetts General Hospital Mass General 2	Boston	Massachusetts
United States	University of Texas/MD Anderson Cancer Center MD Anderson PSC	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall response rate, duration of response, time to response and progression free survival		every 8 weeks of treatment
Secondary	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
Secondary	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