Safety, Pharmacokinetics and Pharmacodynamics of BEZ235 Plus MEK162 in Selected Advanced Solid Tumor Patients - Full Text View

Purpose

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	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific Solid Tumor	Drug: BEZ235 + MEK162	Phase 1


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Genetic and Rare Diseases Information Center resources: Pancreatic Cancer

U.S. FDA Resources

Further study details as provided by Array BioPharma:

Primary Outcome Measures:

Incidence of Dose Limiting Toxicities [ Time Frame: during Cycle 1 of treatment with BEZ235 and MEK162 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: from Cycle 1 Day 1 until treatment discontinuation ] [ Designated as safety issue: Yes ]
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 [ Time Frame: every 8 weeks of treatment ] [ Designated as safety issue: No ]
Time versus plasma concentration profiles of BEZ235 and MEK162 [ Time Frame: during the first cycle of treatment ] [ Designated as safety issue: No ]
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 [ Time Frame: during the first cycle of treatment and at disease progression ] [ Designated as safety issue: No ]
A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination


Enrollment:	29
Study Start Date:	July 2011
Study Completion Date:	March 2013
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BEZ235 + MEK162	Drug: BEZ235 + MEK162

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01337765

Locations


United States, Massachusetts
Massachusetts General Hospital Mass General 2
Boston, Massachusetts, United States, 02114
United States, Texas
University of Texas/MD Anderson Cancer Center MD Anderson PSC
Houston, Texas, United States, 77030-4009
Australia, Victoria
Novartis Investigative Site
Parkville, Victoria, Australia, 3050
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
France
Novartis Investigative Site
Villejuif Cedex, France, 94805
Spain
Novartis Investigative Site
Barcelona, Cataluña, Spain, 08035

Sponsors and Collaborators

Array BioPharma

Investigators


Study Director:	Array BioPharma	303-381-6604

More Information


Responsible Party:	Array BioPharma
ClinicalTrials.gov Identifier:	NCT01337765 History of Changes
Other Study ID Numbers:	CMEK162X2103 2011-000421-74
Study First Received:	April 2, 2011
Last Updated:	February 11, 2016
Health Authority:	United States: Food and Drug Administration Australia: National Health and Medical Research Council Canada: Health Canada France: Ministry of Health Germany: Ministry of Health Spain: Ministry of Health

Keywords provided by Array BioPharma:


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

Additional relevant MeSH terms:


Neoplasms

ClinicalTrials.gov processed this record on September 26, 2016