Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 in Selected Advanced Solid Tumor Patients

September 30, 2020 updated by: Array Biopharma, now a wholly owned subsidiary of Pfizer

A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BKM120 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors

This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of the orally administered phosphatidylinositol 3'-kinase (PI3K) inhibitor BKM120 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (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 BKM120 and MEK162.

Study drugs will be administered once daily orally on a continuous schedule. A treatment cycle is defined as 28 days.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

89

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Pfizer Investigative Site
  • Germany
      • Essen, Germany, 45147
        • Pfizer Investigative Site
      • Heidelberg, Germany, 69120
        • Pfizer Investigative Site
  • Netherlands
      • Utrecht, Netherlands, 3584CX
        • Pfizer Investigative Site
  • Singapore
      • Singapore, Singapore, 169610
        • Pfizer Investigative Site
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Pfizer Investigative Site
  • Switzerland
      • Bellinzona, Switzerland, 6500
        • Pfizer Investigative Site
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Massachusetts General Hospital Mass General 2
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute Study Coordinator
    • New York
      • New York, New York, United States, 90033
        • Memorial Sloan Kettering Cancer Center MSKCC (2)
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Cancer Centers of the Carolinas CCC Faris
    • Texas
      • Houston, Texas, United States, 77030-4009
        • University of Texas/MD Anderson Cancer Center MD Anderson PSC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically/ cytologically confirmed, advanced non resectable solid tumors
  • Measurable or non-measurable, but evaluable disease as determined by RECIST

Exclusion Criteria:

  • Patients with primary CNS tumor or CNS tumor involvement.
  • Diabetes mellitus
  • Unacceptable ocular/retinal conditions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BKM120 + MEK162
Drug: BKM120 + MEK162

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Dose Limiting Toxicities
Time Frame: during Cycle 1 of treatment with BKM120 and MEK162
during Cycle 1 of treatment with BKM120 and MEK162

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of participants with adverse events and serious adverse events.
Time Frame: from Cycle 1 Day 1 until treatment discontinuation
from Cycle 1 Day 1 until treatment discontinuation
Overall response rate, duration of response, time to response and progression free survival
Time Frame: every 8 weeks of treatment
every 8 weeks of treatment
Time versus plasma concentration profiles of BKM120 and MEK162
Time Frame: during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15
during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15
Treatment -induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor.
Time Frame: during the first cycle of treatment on Cycle 1 Day 15 and at disease progression
during the first cycle of treatment on Cycle 1 Day 15 and at disease progression

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Array Biopharma, now a wholly owned subsidiary of Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

December 18, 2017

Study Registration Dates

First Submitted

May 24, 2011

First Submitted That Met QC Criteria

May 31, 2011

First Posted (Estimate)

June 1, 2011

Study Record Updates

Last Update Posted (Actual)

October 5, 2020

Last Update Submitted That Met QC Criteria

September 30, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMEK162X2101
  • 2011-001083-22 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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