Combination of Entinostat and Enzalutamide in Advanced Prostate Cancer

July 26, 2021 updated by: Jianqing Lin, George Washington University

A Phase I Study of Entinostat in Combination With Enzalutamide for Treatment of Patients With Castration-Resistant Prostate Cancer

To determine the safety and tolerability of Entinostat in combination with Enzalutamide in metastatic castrate resistant prostate cancer

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • George Washington University - Medical Faculty Associates

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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 Names:
  • SYND-275 amd MS-275
Drug: Enzalutamide
Dose level 1: 160 mg PO daily. Dose level 2: 160 mg PO daily.
Other Names:
  • MDV3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 3 years
Number of participants who survive without disease progression
3 years
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
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

George Washington University

Investigators

  • Principal Investigator: Jianquig Lin, MD, George Washington Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Actual)

September 1, 2020

Study Completion (Actual)

September 1, 2020

Study Registration Dates

First Submitted

January 26, 2019

First Submitted That Met QC Criteria

February 1, 2019

First Posted (Actual)

February 4, 2019

Study Record Updates

Last Update Posted (Actual)

August 2, 2021

Last Update Submitted That Met QC Criteria

July 26, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GWCC 1000

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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