Phase I/II Study of Entinostat and Lapatinib in Patients With HER2-Positive Metastatic Breast Cancer in Whom Trastuzumab Has Failed
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose (RP2D) for entinostat in combination with
lapatinib (lapatinib ditosylate) in patients who have received trastuzumab for human
epidermal growth factor receptor 2+ (HER2+) metastatic breast cancer.
II. To determine the tumor response to entinostat in combination with lapatinib in patients
who have received trastuzumab for HER2+ metastatic breast cancer in the non-inflammatory
breast cancer (IBC) cohort.
SECONDARY OBJECTIVES:
I. To determine the toxicity of combination therapy with entinostat and lapatinib in
patients who have received trastuzumab for HER2+ metastatic breast cancer.
II. To determine time to tumor progression, time to tumor response, and progression-free
survival (PFS) up to 2 years. (Phase II) III. To determine overall survival at 2 years in
patients who have received trastuzumab for HER2+ metastatic breast cancer.
IV. To determine the toxicity of combination therapy with entinostat and lapatinib in
patients who have received trastuzumab for HER2+ metastatic breast cancer.
EXPLORATORY OBJECTIVES:
I. Determine whether the 2-drug combination modulates the expression of HER2, phosphorylated
HER2 (pHER), epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), protein
kinase B (Akt), and phosphorylated Akt (pAkt) in breast tumors and/or circulating tumor
cells (CTCs).
OUTLINE: This is a phase I, dose-escalation study of entinostat followed by a phase II
study.
Patients receive entinostat orally (PO) on days 1 and 15, and lapatinib tosylate PO on days
1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity. Tumor tissue samples collected at diagnosis and blood samples collected at
baseline and after treatment are analyzed for pEGFR/EGFR, pHER2/HER2, and pAkt/Akt
expression.
After completion of study therapy, patients are followed up for 28 days or until toxicities
are resolved.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
RP2D for entinostat in combination with lapatinib ditosylate (Phase I)
Up to 28 days
No
Naoto Ueno
Principal Investigator
M.D. Anderson Cancer Center
United States: Food and Drug Administration
NCI-2011-03222
NCT01434303
January 2012
Name | Location |
---|---|
M D Anderson Cancer Center | Houston, Texas 77030 |