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Combination of Entinostat and Enzalutamide in Advanced Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03829930
Recruitment Status : Not yet recruiting
First Posted : February 4, 2019
Last Update Posted : April 23, 2019
Sponsor:
Information provided by (Responsible Party):
Jianqing Lin, George Washington University

Tracking Information
First Submitted Date  ICMJE January 26, 2019
First Posted Date  ICMJE February 4, 2019
Last Update Posted Date April 23, 2019
Estimated Study Start Date  ICMJE May 1, 2019
Estimated Primary Completion Date November 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2019)
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
Original Primary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
Safety and tolerability profiles to determine 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
Change History Complete list of historical versions of study NCT03829930 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2019)
  • Progression Free Survival [ Time Frame: 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 [ Time Frame: 18 months ]
    Analysis of immunomodulatory effects of Entinostat
Original Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Progression Free Survival [ Time Frame: 3 years ]
    Number of participants who survive without disease progression
  • Immunomodulatory effects of Entinostat [ Time Frame: 18 months ]
    Changes in circulating T cell subtype, peripheral blood mononuclear cell (PBMC) H3 acetylation, and phenotype of circulating Tregs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination of Entinostat and Enzalutamide in Advanced Prostate Cancer
Official Title  ICMJE A Phase I Study of Entinostat in Combination With Enzalutamide for Treatment of Patients With 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Intervention Model Description:
3+3 Design
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Adenocarcinoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Entinostat and Enzalutamide
Entinostat and Enzalutamide
Interventions:
  • Drug: Entinostat
  • Drug: Enzalutamide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 1, 2019)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2024
Estimated Primary Completion Date November 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Brittany McNamara, BS (202)994-0450 bmcnamara@mfa.gwu.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03829930
Other Study ID Numbers  ICMJE GWCC 1000
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Jianqing Lin, George Washington University
Study Sponsor  ICMJE George Washington University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jianquig Lin, MD George Washington Cancer Center
PRS Account George Washington University
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP