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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Array BioPharma
ClinicalTrials.gov Identifier:
NCT01449058
First received: October 6, 2011
Last updated: February 17, 2017
Last verified: February 2017
  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: Intervention Model: Single Group Assignment
Masking: No masking
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

Further study details as provided by Array BioPharma:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities (DLT) [ Time Frame: during the first cycle (28 days) of treatment with BYL719 and MEK162 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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) ]
    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 ]
    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: December 31, 2018
Primary Completion Date: August 31, 2016 (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   (Adult, Senior)
Sexes Eligible for Study:   All
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

Locations
United States, California
University of California San Diego - Moores Cancer Center Dept Onc
La Jolla, California, United States, 92093-0658
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC
Tampa, Florida, United States, 33612
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital CCPO
Boston, Massachusetts, United States, 02114
United States, New York
Montefiore Medical Center SC
Bronx, New York, United States, 10461
Memorial Sloan Kettering Cancer Center Onc. Dept
NY, New York, United States, 90033
United States, Texas
University of Texas/MD Anderson Cancer Center Dept. of Onc.
Houston, Texas, United States, 77030-4009
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman (3)
Salt Lake City, Utah, United States, 84103
Australia, Victoria
Array BioPharma Investigative Site
Parkville, Victoria, Australia, 3050
France
Array BioPharma Investigative Site
Villejuif Cedex, France, 94805
Italy
Array BioPharma Investigative Site
Milano, MI, Italy, 20133
Array BioPharma Investigative Site
Roma, RM, Italy, 00168
Spain
Array BioPharma Investigative Site
Barcelona, Catalunya, Spain, 08035
Array BioPharma Investigative Site
Barcelona, Catalunya, Spain, 08036
Switzerland
Array BioPharma Investigative Site
Bellinzona, Switzerland, 6500
United Kingdom
Array BioPharma Investigative Site
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Array BioPharma
Investigators
Study Director: Array BioPharma 303-381-6604
  More Information

Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT01449058     History of Changes
Other Study ID Numbers: CMEK162X2109
2011-002578-21 ( EudraCT Number )
Study First Received: October 6, 2011
Last Updated: February 17, 2017

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

ClinicalTrials.gov processed this record on July 24, 2017