A Platform Study of Epigenetic Therapy Before Prostatectomy in Men With Prostate Cancer

IIT2023-10-Posadas-PC-Net : A Platform Study of Epigenetic Therapy Before Prostatectomy in Men With Prostate Cancer

This is an open-label, non-randomized, exploratory platform protocol designed to assess the safety and antitumor activity of epigenetic therapies in participants with localized prostate cancer who are undergoing radical prostatectomy. The epigenetic therapy is intended to increase the sensitivity of the underlying tumor to the patient's immune system. The platform study will evaluate safety, biomarkers, and clinical activity of an epigenetic therapy. The particular details relevant to each module within this platform study will be provided as appendices to the core protocol.

Study Overview

• Status: Recruiting
• Conditions: High-risk Prostate Cancer
• Intervention / Treatment: Drug: Neoadjuvant Epigenetic Therapy

Detailed Description

The study lead investigators will modify and/or add new therapies to the protocol as data emerge from this and other trials. Participants must provide consent for archival biopsy tissue prior to surgery for prostate cancer and must consent to allowing for use of their surgical specimens from biopsy and prostatectomy for biomarker characterization. Given the absence of data in this setting, this pilot proposes this experience with up to 4 weeks of epigenetic agents at doses known to be clinically safe and effective at inducing clinical activity.

Participants will be assigned to receive one of the study interventions and will be monitored for safety and response. The duration of epigenetic therapy will be dependent on the treatment administered and will continue for the duration described in the cohort appendix for each respective combination, unless the participant: is no longer clinically benefiting (NLCB, as evidenced by symptomatic or radiographic disease progression and/or clinical deterioration); experiences any toxicity meeting specified discontinuation criteria (as described in the cohort appendix for each respective combination) or unacceptable toxicity in the best clinical discretion of the treating physician (i.e., Investigator discretion); reaches the maximum duration of study intervention; or withdraws consent.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trial Navigator; Phone Number: 3104232133; Email: cancer.trial.info@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Cancer at SOCC
      • Sub-Investigator: Hyung L Kim, MD
      • Sub-Investigator: Stephen Freedland, MD
      • Sub-Investigator: Michael Ahdoot, MD
      • Sub-Investigator: Jun Gong, MD
      • Contact: Clinical Trial Recruitment Navigator
      • Principal Investigator: Edwin Posadas, MD
      • Sub-Investigator: Andrew Hung, MD
      • Sub-Investigator: Anirban Mitra, MD-PhD
      • Sub-Investigator: Nikka Berkowitz, NP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Men electing to undergo radical prostatectomy with preoperative tissue available.
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

• Adequate organ function defined by:

  • AST and ALT < 2.5 x ULN
  • Total bilirubin < 1.5 x ULN
  • Platelets > 90 x 1000/μL
  • Hemoglobin (Hgb) > 8.5 g/dL
  • Serum Creatinine (Cr) <1.5 x ULN or eGFR > 30 mL/min
• People with partners of childbearing potential in circumstances that may result in the pregnancy, must have had a successful vasectomy (with medically confirmed lack of sperm that are alive) OR must either practice complete abstinence or agree to use adequate contraception (latex or synthetic condom during sexual contact with a female of childbearing potential) from the start of study treatment until 3 months following last dose of study intervention. Subjects should not donate sperm on study, during interruptions in treatment and for 3 months following completion of study drug treatment.
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria

• Active intercurrent illness or malignancy requiring therapy outside of prostate cancer.
• Other anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
• Currently participating in a study using an investigational, medicinal anti-cancer agent within 4 weeks prior to first dose of epigenetic therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant Epigenetic Therapy

Drug: Neoadjuvant Epigenetic Therapy; Participants will be assigned to receive one of the study interventions and will be monitored for safety and response. The duration of epigenetic therapy will be dependent on the treatment administered and will continue for the duration described in the cohort appendix for each respective combination, unless the participant: is no longer clinically benefiting (NLCB, as evidenced by symptomatic or radiographic disease progression and/or clinical deterioration); experiences any toxicity meeting specified discontinuation criteria (as described in the cohort appendix for each respective combination) or unacceptable toxicity in the best clinical discretion of the treating physician (i.e., Investigator discretion); reaches the maximum duration of study intervention; or withdraws consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Using Epigentic Therapy	Safety and tolerability using CTCAE version 5.0. To assess the safety, toxicity, and feasibility of using epigenetic therapy in the neoadjuvant setting for men undergoing radical prostatectomy (RP). Defined by the number of patients who demonstrate treatment related AEs, defined as grade 3 or 4, or grade 2 that causes a dose interruption.	2 Years
Toxicity of Using Epigentic Therapy	Safety and tolerability using CTCAE version 5.0. To assess the safety, toxicity, and feasibility of using epigenetic therapy in the neoadjuvant setting for men undergoing radical prostatectomy (RP). Defined by the number of patients that undergo radical prostatectomy without delay due to epigenetic therapy.	2 Years
Feasibility - % of Patients Able to Undergo Surgery	Feasibility - Percentage of patients able to undergo surgery. To assess the feasibility of measuring changes in gene expression (in radical prostatectomy [RP] tissue) induced by epigenetic therapy at conventional doses (defined by ongoing clinical work focusing on doses within the recommended dose and schedule per the manufacturer where safety has been defined) with a focus on Interferon Stimulated Genes	2 Years
Feasibility - % of patients with grade 3/4 AEs related	Feasibility - Percentage of patients with grade 3/4 adverse events related to epigenetic therapy. To assess the feasibility of measuring changes in gene expression (in radical prostatectomy [RP] tissue) induced by epigenetic therapy at conventional doses (defined by ongoing clinical work focusing on doses within the recommended dose and schedule per the manufacturer where safety has been defined) with a focus on Interferon Stimulated Genes	2 Years
Feasibility - % of patients with evaluable tissue specimens	Feasibility - Percentage of patients with evaluable tissue specimens following epigenetic therapy. To assess the feasibility of measuring changes in gene expression (in radical prostatectomy [RP] tissue) induced by epigenetic therapy at conventional doses (defined by ongoing clinical work focusing on doses within the recommended dose and schedule per the manufacturer where safety has been defined) with a focus on Interferon Stimulated Genes. The evaluability of tissue specimens would be defined as the number of subjects that completed epigenetic therapy and underwent RP and undergo any of the correlative studies using tissue or blood.	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	To estimate the biochemical progression free survival in men treated with epigenetic therapy prior to prostatectomy.	7 Years

Collaborators and Investigators

• Sponsor: Edwin Posadas, MD
• Investigators: Principal Investigator: Edwin Posadas, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 21, 2025

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: PD-L1; radical prostatectomy; Epigenetic Therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: IIT2023-10-Posadas-PC-NET

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No