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
PRIMARY OBJECTIVES:
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)
SECONDARY OBJECTIVES:
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. cluster of
differentiation [CD]4+, CD8+, CD4+/forkhead box P3 [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, fludeoxyglucose F 18) positron
emission tomography (PET)/computed tomography (CT) scan. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of entinostat followed by a phase II
study.
Patients receive entinostat orally (PO) every 2 weeks beginning on day -14 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) version 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
months thereafter.