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Combination of Entinostat and Enzalutamide in Advanced Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03829930
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : August 8, 2019
Sponsor:
Information provided by (Responsible Party):
Jianqing Lin, George Washington University

Study Description
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Brief Summary:
To determine the safety and tolerability of Entinostat in combination with Enzalutamide in metastatic castrate resistant prostate cancer

Condition or disease Intervention/treatment Phase
Prostate Adenocarcinoma Drug: Entinostat Drug: Enzalutamide Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 Design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Entinostat in Combination With Enzalutamide for Treatment of Patients With Castration-Resistant Prostate Cancer
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : November 1, 2022
Estimated Study Completion Date : November 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Entinostat and Enzalutamide
Entinostat and Enzalutamide
 Drug: Entinostat

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.

Other Name: SYND-275 amd MS-275

Drug: Enzalutamide
Dose level 1: 160 mg PO daily. Dose level 2: 160 mg PO daily.
Other Name: MDV3100


Outcome Measures
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Primary Outcome Measures :
  1. Determination of a suitable dose of Entinostat in combination with Enzalutamide [ Time Frame: 18 months ]
    Number of participants who experience an adverse event assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 3 years ]
    Number of participants who survive without disease progression

  2. Changes in circulating T cell subtype, peripheral blood mononuclear cell (PBMC) H3 acetylation, and phenotype of circulating Tregs [ Time Frame: 18 months ]
    Analysis of immunomodulatory effects of Entinostat


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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 exclusion criteria are not to be enrolled in the study:

  • Patient was treated and discontinued Enzalutamide previously for any reason.
  • Major surgery within 28 days or serious infection requiring IV antibiotics within 14 days preceding the first dose of study treatment
  • Patient has received other investigational drugs within 14 days before enrollment.
  • Known GI disease or GI procedure that could impact drug absorption in the upper bowel, or tolerance of Entinostat. Examples include but are not limited to partial gastrectomy, small bowel resection, pancreatectomy, malabsorption or celiac disease
  • Ongoing nausea or vomiting of any severity without improvement after appropriate treatment.
  • > Grade 1 diarrhea, not controlled with appropriate treatment.
  • History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease requiring supplemental oxygen.
  • Clinical and/or radiographic evidence of cerebral metastases. However, patients who have a history of central nervous system (CNS) metastasis but who have no radiographic or clinical evidence of residual tumor (eg, following complete surgical resection or stereotactic radiosurgery) are not excluded from participation in this study.
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any EKG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Serious medical or psychiatric illness or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
  • Any other currently active malignancy (excluding controlled non-melanoma skin cancer). Patients are considered NOT to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
  • Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's Wort within 14 days prior to the first dose of Entinostat and during the study.
  • History of seizure and on active therapy for seizure
  • Known history of uncontrolled human immunodeficiency virus (HIV) infection. HIV positive patients will be allowed if they are on treatment and have an adequate CD4 count (CD4 count >200). Screening is not required in the absence of clinical findings or suspicion.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03829930


Contacts
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Contact: Brittany McNamara, BS (202)994-0450 bmcnamara@mfa.gwu.edu

Locations
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United States, District of Columbia
George Washington University - Medical Faculty Associates Recruiting
Washington, District of Columbia, United States, 20037
Contact: Brittany McNamara, BS    202-994-0450    bmcnamara@mfa.gwu.edu   
Sponsors and Collaborators
George Washington University
Investigators
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Principal Investigator: Jianquig Lin, MD George Washington Cancer Center
More Information
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Additional Information:
NCT00859472  This link exits the ClinicalTrials.gov site NCT00878436  This link exits the ClinicalTrials.gov site

Publications:
Gore SD, Jiemjit A, Silverman LB, et al. Combined methyltransferase/histone deacetylase inhibition with 5-azacitidine and MS-275 in patients with MDS, CMMoL and AML: Clinical response, histone acetylation and DNA damage. Blood 2006; 108: Abstract 517

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Responsible Party: Jianqing Lin, Medical Oncologist, George Washington University
ClinicalTrials.gov Identifier: NCT03829930     History of Changes
Other Study ID Numbers: GWCC 1000
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: August 8, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jianqing Lin, George Washington University:
Castration resistant prostate cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
 Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Entinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action