The purpose of this study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with everolimus in subjects with solid tumors. The escalation part of the study will determine the MTD. The combination will be further explored in the expansion part in subjects with metastatic pancreatic cancer. In addition, subjects with KRAS mutant non-small cell lung cancer will be enrolled.
MEK112110 is a dose-escalation, open-label study to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with everolimus in subjects with solid tumors. This will be accomplished using a dose-escalation procedure starting at low doses of GSK1120212 and everolimus. Dose escalation will continue based on predefined parameters until the maximum tolerated dose is identified. The recommended doses and regimens will be selected based on the safety and pharmacokinetic profiles. The clinical activity of GSK1120212 dosed in combination with everolimus will be explored further in an expansion cohort consisting of 20 subjects with metastatic pancreatic cancer. In addition a substudy will be conducted in 40 subjects with KRAS-mutant non-small cell lung cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
64
Dose escalation will begin at low doses of GSK1120212 and everolimus, then gradually increase in future cohorts. Dose escalation will continue until a recommended combination dose is identified. The recommended combination dose will be used to treat pancreatic and lung cancer patients in later groups in this study.
GSK Investigational Site
Nashville, Tennessee, United States
GSK Investigational Site
San Antonio, Texas, United States
GSK Investigational Site
Paris, France
AEs and changes in laboratory values and vital signs
Time frame: 6 months
Response rate, CR + PR of GSK1120212 and everolimus in KRAS-mutant NSCLC.
Time frame: 6 months
GSK1120212 and everolimus PK parameters following repeat-dose (Day 15) administration of GSK1120212 and everolimus, including AUC(0-tau), Ct, Cmax, tmax, and t1/2, data permitting
Time frame: 6 months
Tumor response as defined by RECIST 1.1.
Time frame: 6 months
CA 19-9 levels compared to radiological response, per RECIST 1.1, over time for each pancreatic cancer subject
Time frame: 6 months
Population PK parameters, oral clearance and oral volume of distribution of GSK1120212 and everolimus will be determined. Dependant upon the final compartmental model describing GSK1120212 + everolimus, add. PK may also be estimated.
Time frame: 6 months
Clinical benefit response rate CR+PR+SD greater than 4mos
Time frame: 6 months
Duration of response
Time frame: 6 months
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