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NCT Number: NCT01449058

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

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.

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Key information

Conditions

Advanced and Selected Solid Tumors AML High Risk and Very High Risk MDS

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Array BioPharma Investigative Site, Parkville, Victoria, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BYL719

Drug

taken orally

MEK162

Drug

taken orally

Primary outcomes

  1. 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 outcomes

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

Sponsors and collaborators

Lead sponsor

Array BioPharma

Industry

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2016
Study completion
2017
First posted
Oct 7, 2011
Registry last updated
Oct 2, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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