Safety, Pharmacokinetics and Pharmacodynamics of BKM120 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:
NCT01363232
First received: May 24, 2011
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors,
Selected Solid Tumors
Drug: BKM120 + MEK162
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 an Orally Administered Combination of BKM120 Plus MEK162 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 [ Time Frame: during Cycle 1 of treatment with BKM120 and MEK162 ] [ Designated as safety issue: Yes ]

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 ]
  • 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 BKM120 and MEK162 [ Time Frame: during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 86
Study Start Date: August 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BKM120 + MEK162 Drug: BKM120 + 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

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
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: NCT01363232

Locations
United States, Massachusetts
Massachusetts General Hospital Mass General 2
Boston, Massachusetts, United States, 02114
United States, Michigan
Wayne State University/Karmanos Cancer Institute Study Coordinator
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center MSKCC (2)
New York, New York, United States, 10021
United States, South Carolina
Cancer Centers of the Carolinas CCC Faris
Greenville, South Carolina, United States, 29605
United States, Texas
University of Texas/MD Anderson Cancer Center MD Anderson PSC
Houston, Texas, United States, 77030-4009
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Heidelberg, Germany, 69120
Netherlands
Novartis Investigative Site
Utrecht, Netherlands, 3584CX
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Barcelona, Cataluña, Spain, 08035
Switzerland
Novartis Investigative Site
Bellinzona, Switzerland, 6500
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: NCT01363232     History of Changes
Other Study ID Numbers: CMEK162X2101, 2011-001083-22
Study First Received: May 24, 2011
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration
Germany: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Spain: Ministry of Health

Keywords provided by Novartis:
BKM120,
MEK162,
RAS RAF mutations,
triple negative breast cancer
pancreatic cancer, ovarian cancer,
NSCLC progressed on EGFR TKI
PI3K inhibitor,
MEK inhibitor

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 30, 2014