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

Phase 1

Completed

• Conditions: Advanced Solid Tumors; Selected Solid Tumors
• Interventions: Drug: BKM120 + MEK162

• Registration Number: NCT01363232
• Lead Sponsor: Array Biopharma, now a wholly owned subsidiary of Pfizer

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 available

Study Timeline

• Study First Submitted: 2011-05-24
• Study First Submitted QC: 2011-05-31
• Study First Posted: 2011-06-01
• Study Start: 2011-08
• Primary Completion: 2014-03
• Study Completion: 2017-12-18
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-30
• Last Update Posted: 2020-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 89

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BKM120 + MEK162	BKM120 + MEK162	-

Primary Outcome Measures

Name	Time	Method
Incidence of Dose Limiting Toxicities	during Cycle 1 of treatment with BKM120 and MEK162

Secondary Outcome Measures

Name	Time	Method
Number of participants with adverse events and serious adverse events.	from Cycle 1 Day 1 until treatment discontinuation
Overall response rate, duration of response, time to response and progression free survival	every 8 weeks of treatment
Time versus plasma concentration profiles of BKM120 and MEK162	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.	during the first cycle of treatment on Cycle 1 Day 15 and at disease progression

Trial Locations

Locations (6)

Memorial Sloan Kettering Cancer Center MSKCC (2); 🇺🇸 New York, New York, United States

Massachusetts General Hospital Mass General 2; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Institute Study Coordinator; 🇺🇸 Detroit, Michigan, United States

University of Texas/MD Anderson Cancer Center MD Anderson PSC; 🇺🇸 Houston, Texas, United States

Cancer Centers of the Carolinas CCC Faris; 🇺🇸 Greenville, South Carolina, United States

Pfizer Investigative Site; 🇨🇭 Bellinzona, Switzerland