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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01363232
Recruitment Status : Completed
First Posted : June 1, 2011
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Array BioPharma

Tracking Information
First Submitted Date  ICMJE May 24, 2011
First Posted Date  ICMJE June 1, 2011
Last Update Posted Date January 23, 2018
Study Start Date  ICMJE August 2011
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2011)
Incidence of Dose Limiting Toxicities [ Time Frame: during Cycle 1 of treatment with BKM120 and MEK162 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 31, 2011)
Incidence of Dose Limiting Toxicities [ Time Frame: during Cycle 1 of treatment with BEZ235 and MEK162 ]
Change History Complete list of historical versions of study NCT01363232 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2012)
  • Number of participants with adverse events and serious adverse events. [ Time Frame: 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2011)
  • Number of participants with adverse events and serious adverse events. [ Time Frame: 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 ]
  • Time versus plasma concentration profiles of BEZ235 and MEK162 [ Time Frame: 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 and skin [ Time Frame: during the first cycle of treatment on Cycle 1 Day 15 and at disease progression ]
  • Molecular status (genetic alterations, protein expression and/or activation) of markers related to PI3K and ERK signaling in tumor tissue and blood and their potential relationship to clinical responses. [ Time Frame: at baseline (pre-treatment) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 in Selected Advanced Solid Tumor Patients
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Selected Solid Tumors
Intervention  ICMJE Drug: BKM120 + MEK162
Study Arms  ICMJE Experimental: BKM120 + MEK162
Intervention: Drug: BKM120 + MEK162
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 5, 2015)
89
Original Estimated Enrollment  ICMJE
 (submitted: May 31, 2011)
58
Actual Study Completion Date  ICMJE December 18, 2017
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   Netherlands,   Singapore,   Spain,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01363232
Other Study ID Numbers  ICMJE CMEK162X2101
2011-001083-22 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Array BioPharma
Study Sponsor  ICMJE Array BioPharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Array BioPharma 303-381-6604
PRS Account Array BioPharma
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP