A Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer

NCT ID: NCT04179864

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-18

Study Completion Date

2024-11-04

Brief Summary

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This is a global, multi-center, open-label, randomized phase 1b/2, active-controlled safety and efficacy study of oral administration of tazemetostat in combination with enzalutamide or abiraterone/prednisone (phase 1b) versus enzalutamide or abiraterone/prednisone alone in asymptomatic or mildly symptomatic subjects with progressive, metastatic castration-resistant prostate cancer (mCRPC) who have progressed on either abiraterone acetate, enzalutamide, or apalutamide or who are second generation anti-androgen treatment naive, and who have not received chemotherapy for mCRPC.

This study is designed to determine the recommended phase 2 doses (RP2D) of tazemetostat in combination with either enzalutamide or abiraterone/prednisone, based on safety, tolerability, pharmacokinetic, pharmacodynamic, and efficacy profiles.

Detailed Description

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Conditions

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Metastatic Prostate Cancer Metastatic Castration-resistant Prostate Cancer

Keywords

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metastatic castration resistant prostate cancer tazemetostat EPZ-6438 E7438 enzalutamide abiraterone Prednisone Zytiga Xtandi

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1b: Tazemetostat in Combination with Abiraterone/Prednisone

In Phase 1b, abiraterone/prednisone will be administered in combination with tazemetostat in cycle 1 (28 days) to establish the recommended dose of tazemetostat in this combination; participants may continue treatment in additional 28-day cycles, as tolerated, until progression or unacceptable toxicity

Group Type EXPERIMENTAL

Tazemetostat

Intervention Type DRUG

Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene

Abiraterone/prednisone

Intervention Type DRUG

1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily in combination with prednisone 5 mg administered orally twice daily.

Phase 1b: Tazemetostat in Combination with Enzalutamide

In Phase 1b, enzalutamide will be administered in combination with tazemetostat in cycle 1 (28 days) to establish the recommended dose of tazemetostat in this combination; participants may continue treatment in additional 28-day cycles, as tolerated, until progression or unacceptable toxicity

Group Type EXPERIMENTAL

Tazemetostat

Intervention Type DRUG

Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene

Enzalutamide

Intervention Type DRUG

enzalutamide 160 mg (four 40 mg capsules) orally once daily

Phase 2: Tazemetostat in Combination with Enzalutamide

Participants will receive the newly established recommended phase 2 dose, orally twice daily when given in combination with enzalutamide) as determined in phase 1b part of the study) or enzalutamide alone.

All participants will receive treatment in 28-day cycles.

Group Type EXPERIMENTAL

Tazemetostat

Intervention Type DRUG

Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene

Enzalutamide

Intervention Type DRUG

enzalutamide 160 mg (four 40 mg capsules) orally once daily

Phase 2: Enzalutamide only

In Phase 2, Enzalutamide will be administered on cycle 1 day 1

Group Type ACTIVE_COMPARATOR

Enzalutamide

Intervention Type DRUG

enzalutamide 160 mg (four 40 mg capsules) orally once daily

Interventions

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Tazemetostat

Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene

Intervention Type DRUG

Abiraterone/prednisone

1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily in combination with prednisone 5 mg administered orally twice daily.

Intervention Type DRUG

Enzalutamide

enzalutamide 160 mg (four 40 mg capsules) orally once daily

Intervention Type DRUG

Other Intervention Names

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EPZ-6438 E7438 IPN60200 Zytiga Xtandi

Eligibility Criteria

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Inclusion Criteria

1. Age at the time of consent ≥ 18 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (Appendix
3. Life expectancy of \> 3 months.
4. Histologically or cytologically confirmed adenocarcinoma of the prostate. Small cell or neuroendocrine tumors of the prostate are also permitted.
5. Progressive disease in the setting of medical or surgical castration (ie, castration- resistant prostate cancer \[CRPC\]) by PCWG3 criteria for study entry.

* Evidence of disease progression by rising PSA or
* Soft tissue progression per RECIST 1.1 or
* Evidence of disease progression by observation of 2 new bone lesions since the initiation of last systemic therapy.
6. Metastatic prostate cancer disease, documented by the following imaging

• Bone lesions on bone scan (per PCWG3) or by soft tissue disease (per RECIST 1.1) by CT/MRI imaging Must have undergone bilateral orchiectomy or be willing to continue GnRH analogue or antagonist.
7. Prior treatment with a second-generation androgen inhibitor as follows:

* For phase 1b, EITHER Previously untreated with or progressed on a second generation androgen inhibitor (abiraterone, enzalutamide, or apalutamide) OR progressed on a second generation inhibitor (inhibitor (abiraterone, enzalutamide, or apalutamide)
* For phase 2 randomized component (i.e, enzalutamide- containing treatment arms) of the study, previously progressed on abiraterone.

* Prior radionuclide therapy within 4 weeks.
* Another interventional product or standard agent in a clinical study within 28 days prior to the first planned dose of Tazemetostat
* For phase 2 subjects to be randomized to one of the enzalutamide treatment arms only, prior treatment with the second-generation androgen antagonist including enzalutamide, apalutamide, darolutamide, and proxalutamide, etc.
3. Severe concurrent disease, infection, or comorbidity that, in the judgment of the Investigator, would make the subject inappropriate for enrollment
4. Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2.

Exclusion Criteria

1. Known symptomatic brain metastases
2. Treatment with any of the following for prostate cancer within the indicated timeframe prior to day 1 of starting study treatment:

* First generation: AR antagonists (eg, bicalutamide, nilutamide, flutamide) within 4 weeks.
* 5-alpha-reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol), or progesterones within 2 weeks.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Epizyme, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

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Genesis Healthcare Partners

San Diego, California, United States

Site Status

The Urology Center Of Colorado

Denver, Colorado, United States

Site Status

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Site Status

XCancer - Northwest Oncology and Hematology

Rolling Meadows, Illinois, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Comprehensive Cancer Centers of Nevada - Central Valley

Las Vegas, Nevada, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Associated Medical Professionals of NY, PLLC - Urology

Syracuse, New York, United States

Site Status

Montefiore Einstein Center for Cancer Care

The Bronx, New York, United States

Site Status

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

SCRI - Tennessee Oncology Chattanooga

Chattanooga, Tennessee, United States

Site Status

Urology Associates P.C.

Hendersonville, Tennessee, United States

Site Status

XCancer - Tennesee Cancer Specialists

Knoxville, Tennessee, United States

Site Status

SCRI - Tennessee Oncology Nashville

Nashville, Tennessee, United States

Site Status

Urology San Antonio

San Antonio, Texas, United States

Site Status

Academisch Ziekenhuis Groeninge Campus Kennedylaan

Kortrijk, West Vlaanderen, Belgium

Site Status

Hospital Universitario de Jerez de la Frontera

Jerez de la Frontera, Cadiz, Spain

Site Status

Hospital de la Santa Creu i. Sant Pau

Barcelona, , Spain

Site Status

Hospital del Mar Parc de Salut Mar

Barcelona, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status

Countries

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United States Belgium Spain

Other Identifiers

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2019-003649-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EZH-1101

Identifier Type: -

Identifier Source: org_study_id