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

NCT06888102 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: IIT2023-10-Posadas-PC-NET
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

High-risk Prostate Cancer

Keywords

Epigenetic Therapy; PD-L1; radical prostatectomy

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• Progression Free Survival

  7 Years

Study Arms (1)

Neoadjuvant Epigenetic Therapy

EXPERIMENTAL

Drug: Neoadjuvant Epigenetic Therapy

Interventions

Neoadjuvant Epigenetic Therapy DRUG

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.

Neoadjuvant Epigenetic Therapy

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Edwin Posadas, MD: lead

Study Sites (1)

Cedars-Sinai Cancer at SOCC

Los Angeles, California, 90048, United States

RECRUITING

Study Officials

• Edwin Posadas, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Navigator

CONTACT

3104232133; cancer.trial.info@cshs.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: This is an open-label, non-randomized platform protocol opening multiple modules, not running concurrently. Each module will enroll 20 patients. Module A will use open-label azacitidine in the neoadjuvant setting for patients with a diagnosis of prostate cancer undergoing radical prostatectomy.

Study Record Dates

• First Submitted: October 11, 2024
• First Posted: March 21, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: February 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)