Prostate Adenocarcinoma
Conditions
Keywords
Castration resistant prostate cancer
Brief summary
To determine the safety and tolerability of Entinostat in combination with Enzalutamide in metastatic castrate resistant prostate cancer
Detailed description
This study is designed to determine the safety and tolerability of Entinostat with Enzalutamide for treatment of patients with castration-resistant prostate cancer. There will be two dose levels of Entinostat in combination with same dose of Enzalutamide. Patients will be followed during treatment and 1 month post discontinuation.
Interventions
DRUGEntinostat
Entinostat is formulated for oral administration. A food effect is evident for entinostat; exposure is significantly reduced when entinostat is administered with a high fat meal. Accordingly, entinostat is to be administered on an empty stomach, at least 1 hour before and 2 hours after a meal. Entinostat tablets should not be split, crushed, or chewed. Consult the individual clinical protocols for specific dosing instructions. Dose level 1: 3mg PO weekly. Dose level 2: 5mg PO weekly.
DRUGEnzalutamide
Dose level 1: 160 mg PO daily. Dose level 2: 160 mg PO daily.
Sponsors
George Washington University
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3+3 Design
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each patient must meet all of the following inclusion criteria to be enrolled in the study: * Age \>/= 18 years and are capable of giving informed consent. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Patients must have a pathologically confirmed diagnosis of prostate adenocarcinoma. Features of neuroendocrine phenotype are allowed. * Patients must have evidence of castration resistant metastatic disease and eligible for Enzalutamide per standard guidelines. Castration resistant non-metastatic disease is allowed in phase I study if subject is candidate for Enzalutamide. * Patients must have and ECOG performance status of ≤ 2.(appendix D) * Patients must be on continuous LHRH agonist or antagonist treatment or surgically castrated with castrate levels of testosterone (\< 20 ng/dl). * Any number of prior chemotherapy regimens are allowed. Chemotherapy naïve patients are allowed. * If patient is already on Enzalutamide at a dose of 160mg daily, he is allowed if he can have baseline image and PSA within 1 month of the start of entinostat. * Patients may have had androgen synthesis inhibitors or other investigational drugs. Patient must have discontinued flutamide or nilutamide or other AR targeted agents (including abiraterone) for at least 4 weeks and bicalutamide for at least 6 weeks prior to day 1 of treatment. * Patients receiving treatment with bisphosphonates or denosumab must remain on treatment during the study. * Patients must not require concurrent radiation or other chemotherapy while receiving protocol therapy. Patients may have received previous radiation but must have completed radiation at least 4 weeks (8 weeks for radiation to the brain) prior to registration. * Patients must have recovered to grade ≤ 1 from all acute toxicity of previous radiation, hormonal or chemotherapy treatments. * Patient agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of entinostat. * Adequate renal function as defined by serum creatinine ≤ 1.5 x ULN. If creatinine \>1.5 x ULN, calculated or measured creatinine clearance must be ≥ 60 mL/minute (Cockcroft-Gault). * ANC \> 1500/mm³, platelets \> 100,000/mm³, Hgb \> 9 g/dL. * Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT)\< 1.5 x ULN. AST and/or ALT may be up to 5X ULN in the setting of known liver metastasis.
Exclusion criteria
Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of a suitable dose of Entinostat in combination with Enzalutamide | 18 months | Number of participants who experience an adverse event assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 3 years | Number of participants who survive without disease progression |
| Changes in circulating T cell subtype, peripheral blood mononuclear cell (PBMC) H3 acetylation, and phenotype of circulating Tregs | 18 months | Analysis of immunomodulatory effects of Entinostat |
Countries
United States
Outcome results
None listed