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

NCT01363232 | Completed Phase 1

• 2 other identifiers: CMEK162X21012011-001083-22
• Study Type: interventional
• Target: 89
• Locations: 7 countries
• Sites: 12

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.

Conditions

Advanced Solid Tumors; Selected Solid Tumors

Keywords

BKM120; MEK162; RAS RAF mutations; triple negative breast cancer; pancreatic cancer, ovarian cancer; NSCLC progressed on EGFR TKI; PI3K inhibitor; MEK inhibitor

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting Toxicities

  during Cycle 1 of treatment with BKM120 and MEK162

Secondary Outcomes (4)

• 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

Study Arms (1)

BKM120 + MEK162

EXPERIMENTAL

Drug: BKM120 + MEK162

Interventions

BKM120 + MEK162 DRUG

BKM120 + MEK162

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Array Biopharma, now a wholly owned subsidiary of Pfizer: lead

Study Sites (12)

Massachusetts General Hospital Mass General 2

Boston, Massachusetts, 02115, United States

Location

Karmanos Cancer Institute Study Coordinator

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering Cancer Center MSKCC (2)

New York, New York, 90033, United States

Location

Cancer Centers of the Carolinas CCC Faris

Greenville, South Carolina, 29605, United States

Location

University of Texas/MD Anderson Cancer Center MD Anderson PSC

Houston, Texas, 77030-4009, United States

Location

Pfizer Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Pfizer Investigative Site

Essen, 45147, Germany

Location

Pfizer Investigative Site

Heidelberg, 69120, Germany

Location

Pfizer Investigative Site

Utrecht, 3584CX, Netherlands

Location

Pfizer Investigative Site

Singapore, 169610, Singapore

Location

Pfizer Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Pfizer Investigative Site

Bellinzona, 6500, Switzerland

Location

Related Publications (1)

• Bardia A, Gounder M, Rodon J, Janku F, Lolkema MP, Stephenson JJ, Bedard PL, Schuler M, Sessa C, LoRusso P, Thomas M, Maacke H, Evans H, Sun Y, Tan DSW. Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. Oncologist. 2020 Jan;25(1):e160-e169. doi: 10.1634/theoncologist.2019-0297. Epub 2019 Aug 8.

  PMID: 31395751 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms

Interventions

NVP-BKM120; binimetinib

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders

Study Officials

• Pfizer CT.gov Call Center

  1-800-718-1021

  STUDY DIRECTOR

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2011
• First Posted: June 1, 2011
• Study Start: August 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: December 18, 2017
• Last Updated: October 5, 2020

Record last verified: 2020-09

Locations

CH (1); DE (2); SG (1); CA (1); NL (1); ES (1); US (5)