A Study of Tazemetostat (Tazverik) Before Prostatectomy in Men With Prostate Cancer

IIT2021-09-Posadas-NA-TAZ: A Study of Tazemetostat (Tazverik) Before Prostatectomy in Men With Prostate Cancer

This study is an open-label, single-arm, pilot, perioperative study of EZH2 inhibition in patients undergoing Radical Prostatectomy (RP). The EZH2 inhibition is intended to increase the sensitivity of the underlying tumor to the patient's immune system.

Given the absence of data in this setting, we propose to pilot this experience with 4 weeks of tazemetostat at doses known to be clinically safe and effective at inducing clinical effects via inhibition of EZH2 as established for follicular lymphoma and epithelioid sarcoma: 800 mg twice daily with or without food.

Prior to tazemetostat, blood will be collected (4 tubes) for immune cells, Circulating Tumor Cells, and plasma. This will be repeated at the time of RP. RP tissues will be collected.

Additionally, patients will have a week lead-in to wear a FitBit Charge 5TM device (or similar model) to continuously monitor physical activity from baseline up until end of study. The start of the week lead-in will be considered the baseline visit. Subjects will also be asked to continue wearing the device until end of study and option to continue for up to 2 years after end of study in follow-up.

Study Overview

• Status: Withdrawn
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Tazverik

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men electing to undergo radical prostatectomy with preoperative tissue available
• Able to take oral medications
• Age ≥18 years
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Adequate organ function
• Men with partners of childbearing potential, 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
• Inclusion criteria for remote monitoring component of study with Fitbit only (failure to meet inclusion criterion for Fitbit-monitoring portion of study should not preclude participating in treatment trial): Access to a device (e.g., smart phone, tablet) that has the capability to sync to the Fitbit. Note: access can be via family member, friend, caregiver, or study-designated device provided by study member

Exclusion Criteria:

• Active intercurrent illness or malignancy requiring therapy outside of prostate cancer
• History of bleeding disorders
• Concurrent use of anti-platelet agents or therapeutic anticoagulants with the exception of low-dose aspirin (81 mg daily) or NSAIDs for pain/inflammation.

Concurrent use of strong and moderate CYP3A inhibitors and inducers

• Subjects who have previously received tazemetostat
• Currently participating in a study using an investigational, medicinal anti-cancer agent within 4 weeks prior to first dose of tazemetostat
• Exclusion criteria for remote monitoring component of study with Fitbit only (failure to meet exclusion criterion for Fitbit-monitoring portion of study should not preclude participating in treatment trial): Using a pacemaker, implantable cardiac defibrillator, neurostimulator, cochlear implants (removable hearing aids permitted), or other electronic medical equipment, per PI's discretion.

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: Tazemetostat; Tazemetostat 200 mg oral tablets; 800 mg by mouth twice daily for 28 days	Drug: Tazverik; Tazemetostat (Tazverik) 200 mg oral tablets; 800 mg by mouth twice daily for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events, serious adverse events, and treatment-related adverse events.	Evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From start of study treatment until confirmation of disease progression, intolerable toxicities, or withdrawal of consent, whichever came first. Assessed up to 30 days following last dose of study treatment.
Proportion of patients able to undergo surgery		At time of surgery
Proportion of patients with Grade 3 or above treatment related adverse events	Grade 3 or above treatment related adverse events as assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From start of study treatment until confirmation of disease progression, intolerable toxicities, or withdrawal of consent, whichever came first. Assessed up to 30 days following last dose of study treatment.
Proportion of patients with evaluable tissue specimens following tazemetostat		At time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Progression Free Survival	Defined by a detectable post-operative prostate-specific antigen (PSA)	From the start of study treatment until documented progression, or death due to any cause. Assessed up to 5 years.

Collaborators and Investigators

• Sponsor: Edwin Posadas, MD
• Collaborators: Epizyme, Inc.
• Investigators: Principal Investigator: Edwin Posadas, MD FACP, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Prostate cancer; Radical prostatectomy; RP
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: IIT2021-09-Posadas-NA-TAZ

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.: Yes