A Phase I Study to Assess the Food Effect on the Pharmacokinetics of Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic ER+ Breast Cancer and Men and Women With Progressive Non-Small Cell Lung Cancer
This is Phase 1, randomized, open-label, study of entinostat. The study is designed to
evaluate any food effect on the pharmacokinetics of entinostat.
Patients will be randomized to receive entinostat with or without food on Cycle 1 Day 1
(C1D1). Patients randomized to receive entinostat with food on C1D1 will receive a second
dose of entinostat without food on Cycle 1 Day 15 (C1D15). Patients randomized to receive
entinostat without food on C1D1 will receive a second dose of entinostat with food on C1D15.
Each cycle in the study will be for 28 days duration. Blood samples will be obtained
pre-dose and serial blood samples will be taken after each dose to assess pharmacokinetics.
For Cycle 2 and all subsequent cycles, all patients will continue to receive entinostat on
Days 1 and 15 of each cycle. Those with breast cancer will also receive exemestane orally
once daily starting on Cycle 2 Day 1. Those with NSCLC will also receive erlotinib starting
on Cycle 2 Day 1.
Patients will be assessed at screening and at pre-prescribed times during study enrollment
using standard assessments. Patients will also be assessed for tumor response after each 2
cycles. Patients will continue receiving study treatment until tumor progression or adverse
events occur which necessitate discontinuing therapy as determined by the Investigator.
Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Difference in pharmacokinetics of entinostat when subjects fed or fasted
The pharmacokinetics of entinostat will be analyzed from patient plasma samples: maximum plasma concentration, time of maximum plasma concentration, area under the plasma concentration-time curve from baseline to last measurable concentration and extrapolated to infinity, terminal elimination rate constant.
C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), 16, 18, 20, 22 25; C2D1
William McCulloch, M.D.
United States: Food and Drug Administration
|Florida Cancer Specialists||Fort Myers, Florida 33901|
|Sarah Cannon Research Institute||Nashville, Tennessee 37203|
|Peggy and Charles Stephenson Cancer Center||Oklahoma City, Oklahoma 73104|