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

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ClinicalTrials.gov Identifier: NCT01337765
Recruitment Status : Completed
First Posted : April 19, 2011
Last Update Posted : February 12, 2016
Sponsor:
Information provided by (Responsible Party):
Array BioPharma

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
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
Study Start Date : July 2011
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013
Arms and Interventions
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Arm Intervention/treatment
Experimental: BEZ235 + MEK162 Drug: BEZ235 + MEK162


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities [ Time Frame: 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 :
  1. Number of participants with adverse events and serious adverse events [ Time Frame: 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

  2. Overall response rate, duration of response, time to response and progression free survival [ Time Frame: every 8 weeks of treatment ]
  3. Time versus plasma concentration profiles of BEZ235 and MEK162 [ Time Frame: during the first cycle of treatment ]
    A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination

  4. 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 ]
    A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT01337765     History of Changes
Other Study ID Numbers: CMEK162X2103
2011-000421-74 ( EudraCT Number )
First Posted: April 19, 2011    Key Record Dates
Last Update Posted: February 12, 2016
Last Verified: February 2016

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
Dactolisib
Antineoplastic Agents