A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01449058
First received: October 6, 2011
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

This is a multi-center, open-label, dose-finding, phase Ib study to estimate the maximum tolerated dose(s) (MTD(s)) and/or recommended dose(s) for expansion (RDE(s)) for the orally administered combination of BYL719 and MEK162. This combination will be explored in adult patients with advanced CRC, esophageal cancer, pancreatic cancer, NSCLC, ovarian cancer, or other advanced solid tumors and in adult patients with AML or high risk and very high risk MDS, with documented RAS or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RDE, four expansion arms will be opened in order to further assess the safety and preliminary activity of the combination of BYL719 and MEK162 in specific patient populations.


Condition Intervention Phase
Advanced and Selected Solid Tumors, AML, High Risk and Very High Risk MDS
Drug: BYL719 plus MEK162
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
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 Orally Administered MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities (DLT) [ Time Frame: during the first cycle (28 days) of treatment with BYL719 and MEK162 ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 unless otherwise specified. A DLT is defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤ 28 days following the first dose of BYL719 and MEK162 (Cycle 1), and meets any of the protocol-specified DLT criteria.


Secondary Outcome Measures:
  • Number of participants with adverse events and serious adverse events [ Time Frame: Assessed from Cycle 1 Day 1 until treatment discontinuation ] [ Designated as safety issue: Yes ]
    All AEs and SAEs will be collected in accordance with the protocol and assessed for relatedness to study drug combination.

  • Overall response rate [ Time Frame: Assessed every 8 weeks until disease progression ] [ Designated as safety issue: No ]
    Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR).

  • Time to progression [ Time Frame: Assessed every 8 weeks until disease progression ] [ Designated as safety issue: No ]
    Time to progression (TTP) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient has not had an event, time to progression is censored at the date of last adequate tumor assessment.

  • Progression free survival [ Time Frame: Assessed every 8 weeks until disease progression ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

  • Time versus plasma concentration profiles of BYL719 and MEK162 [ Time Frame: Assessed during the first cycle of treatment ] [ Designated as safety issue: No ]
    Blood concentrations of MEK162 and its metabolite (AR00426032) and BYL719 will be assessed during the first cycle of treatment.

  • Correlation of baseline mutation or amplification status (PIK3CA, KRAS, NRAS and BRAF) and clinical anti-tumor activity outcome [ Time Frame: Assessed at Baseline (pre-treatment) ] [ Designated as safety issue: No ]
    Collect baseline genetic mutation/alteration status to investigate the potential relationship to anti-tumor activity.

  • Clinical benefit rate [ Time Frame: Assessed every 4 weeks for 3 months and every 3 months for 6 months followed by every 6 months thereafter until disease progression ] [ Designated as safety issue: No ]
    The clinical benefit rate is defined as the proportion of patients with complete remission, complete remission with incomplete blood count recovery, partial remission, minor response or stable disease for > 15 weeks


Estimated Enrollment: 138
Study Start Date: March 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BYL719 + MEK162
BYL719 plus MEK162. Dose escalation with a starting dose for the first cohort of 200mg QD BYL719 and 30mg BID MEK162
Drug: BYL719 plus MEK162
BYL719 plus MEK162 administered in this dose escalation study until MTD/RDE is achieved, followed by a dose expansion phase.

  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 solid tumors, AML or high risk and very high risk MDS
  • Measurable disease as determined by RECIST 1.1

Exclusion Criteria:

  • Primary CNS tumor or CNS tumor involvement
  • Diabetes mellitus
  • Unacceptable ocular/retinal conditions
  • Clinically significant cardiac disease or impaired cardiac function
  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: NCT01449058

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, California
University of California San Diego Dept Onc Recruiting
La Jolla, California, United States, 92093-0658
Contact: Elisa Arthur    858-822-5367    eparthur@ucsd.edu   
Principal Investigator: Steven Plaxe         
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Sumin Hassani    813-745-1807    simin.hassani@moffitt.org   
Principal Investigator: Anthony Magliocco         
United States, Illinois
Northwestern University Onc Dept. Recruiting
Chicago, Illinois, United States, 60611
Contact: Roxana Vintilescu    312-695-1365    Claudia.vintilescu@northwestern.edu   
Principal Investigator: Melissa Johnson         
United States, Massachusetts
Massachusetts General Hospital CCPO Recruiting
Boston, Massachusetts, United States, 02114
Contact: Dejan Juric    617-724-4000      
Principal Investigator: Dejan Juric         
United States, New York
Memorial Sloan Kettering Cancer Center Onc. Dept Not yet recruiting
New York, New York, United States, 10021
Contact: Travis Marshall       marshat1@mskcc.org   
Principal Investigator: Raajit Rampal         
United States, Texas
University of Texas/MD Anderson Cancer Center Dept. of Onc. Recruiting
Houston, Texas, United States, 77030-4009
Contact: Vanda Stepanek    713-563-1193    vstepane@mdanderson.org   
Principal Investigator: Filip Janku         
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman (3) Recruiting
Salt Lake City, Utah, United States, 84103
Contact: Thaylon Davis       Thaylon.Davis@hci.utah.edu   
Principal Investigator: Sunil Sharma         
Australia, Victoria
Novartis Investigative Site Recruiting
Parkville, Victoria, Australia, 3050
France
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Italy
Novartis Investigative Site Not yet recruiting
Milano, MI, Italy, 20141
Novartis Investigative Site Not yet recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Not yet recruiting
Roma, RM, Italy, 00168
Novartis Investigative Site Not yet recruiting
Roma, RM, Italy, 00133
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Switzerland
Novartis Investigative Site Recruiting
Bellinzona, Switzerland, 6500
United Kingdom
Novartis Investigative Site Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01449058     History of Changes
Other Study ID Numbers: CMEK162X2109, 2011-002578-21
Study First Received: October 6, 2011
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration (TGA)
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Switzerland: Swissmedic

Keywords provided by Novartis:
Advanced solid tumor,
AML
high risk and very high risk MDS
dose escalation,
RAS/BRAF mutation,
PI3K inhibitor,
MEK inhibitor,
BYL719,
MEK162

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 29, 2014