Phase I/II Study of High Dose Interleukin 2, Aldesleukin, in Combination With the Histone Deacetylase Inhibitor Entinostat in Patients With Metastatic Renal Cell Carcinoma
I. To evaluate the safety and tolerability of high dose interleukin 2 (aldesleukin) in
combination with entinostat in patients with metastatic renal cell carcinoma (RCC). (Phase
I) II. To monitor toxicity and estimate the efficacy of high dose aldesleukin combined with
entinostat in patients with metastatic RCC. (Phase II)
I. To compare the time-to-tumor progression, progression-free survival and overall survival
of patients with metastatic RCC treated with high dose aldesleukin combined with entinostat
to the historical data of patients treated with high dose aldesleukin alone. (Phase II) II.
To assess the toxicity of high dose aldesleukin combined with entinostat. (Phase II) III. To
evaluate entinostat pharmacodynamics (PD) in blood and tumor samples. (Phase II) IV. To
measure the association between baseline laboratory parameters (e.g. CD4+, CD8+,
CD4+/Foxp3), tumor blood metabolism, and a variety of response variables (e.g. toxicity,
response and survival). (Phase II) V. To explore the relationship between entinostat
exposure with PD endpoints (e.g. toxicity and histone acetylation in peripheral blood
mononuclear cells or peripheral blood mononuclear cells (PBMNCs) and changes in T cell
subset population). (Phase II) VI. To evaluate the modulation of tumor metabolism by
fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan.
OUTLINE: This is a dose-escalation study of entinostat.
Patients receive entinostat orally (PO) every 2 weeks and high-dose aldesleukin
intravenously (IV) every 8 hours on days 1-5 and 15-19. Courses repeat every 84 days* in the
absence of disease progression or unacceptable toxicity.
NOTE: *Patients with evidence of tumor shrinkage may receive up to 3 courses of high-dose
aldesleukin therapy. Patients with stable disease by Response Evaluation Criteria In Solid
Tumors (RECIST) V.1.0 criteria, but without evidence of tumor shrinkage after two courses
will receive only entinostat until disease progression is documented.
After completion of study treatment, patients are followed up at 30 days and then every 3
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended dose of the biologic agent, entinostat, when combined with IL-2 (Phase I)
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Ohio State University Medical Center||Columbus, Ohio 43210|
|USC Norris Comprehensive Cancer Center||Los Angeles, California 90089|