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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01337765
First received: April 2, 2011
Last updated: February 25, 2013
Last verified: February 2013
History of Changes
  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: Parallel 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
U.S. FDA Resources

Further study details as provided by Novartis:

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


Estimated Enrollment: 80
Study Start Date: July 2011
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: June 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
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
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
MD Anderson Cancer Center/University of Texas MD Anderson PSC
Houston, Texas, United States, 77030-4009
United States, Wisconsin
University of Wisconsin Univ Wisc
Madison, Wisconsin, United States, 53792
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
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Investigative Site
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01337765     History of Changes
Other Study ID Numbers: CMEK162X2103, 2011-000421-74
Study First Received: April 2, 2011
Last Updated: February 25, 2013
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 Novartis:
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 May 19, 2013