Study Stopped
The study was terminated early as Sponsor decided to discontinue the development of tazemetostat in metastatic castration resistant prostate cancer and the primary endpoint was not met for this study. There were no safety concerns.
A Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer
CELLO-1
CELLO-1: A Phase 1b/2 Open-Label Study Evaluating Tazemetostat in Combination With Enzalutamide or Abiraterone/Prednisone in Chemotherapy Naive Subjects With Metastatic Castration-Resistant Prostate Cancer
2 other identifiers
interventional
102
3 countries
24
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2019
Longer than P75 for phase_1
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 14, 2019
CompletedStudy Start
First participant enrolled
November 18, 2019
CompletedFirst Posted
Study publicly available on registry
November 27, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 4, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
November 4, 2024
CompletedResults Posted
Study results publicly available
March 10, 2026
CompletedMarch 10, 2026
February 1, 2026
5 years
November 14, 2019
November 3, 2025
February 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase 1b: Number of Participants With Treatment-Emergent Non-Serious Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs)
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product and which did not necessarily had a causal relationship with this study drug. An SAE was an AE which occurred during any study phase and at any dose of study drug, that fulfilled 1 or more of following: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability or incapacity, was a congenital abnormality or birth defect, or was an important medical event that might jeopardize the participant or might require medical intervention to prevent one of the outcomes listed above. TEAEs were AEs that started or worsened in severity on or after the date of the first dose of study drug through 30 after the end of study drug, or prior to initiation of another investigational agent or cytotoxic chemotherapy. The treatment-emergent non-serious AEs are presented with a frequency threshold of 5%.
From first dose of study drug (Day 1) up to either 30 days after last dose of study drug or until the initiation of subsequent anticancer therapy or end of treatment visit. Assessed up to 149 weeks
Phase 1b: Recommended Phase 2 Dose (RP2D) of Tazemetostat
RP2D was based on pharmacokinetics (PK) parameters, pharmacodynamics (PD) parameters as well as efficacy and the overall tolerability of each combination (tazemetost with enzalutamide or tazemetostat with abiraterone/prednisone).
From Day 1 up to Day 28 of Cycle 1 (each cycle was 28 days)
Phase 2: Radiographic Progression-Free Survival (rPFS)
rPFS was defined as the time from date of randomization (phase 2)/date of first dose of study drug (phase 1b) to the first objective evidence of radiographic progression using response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) (soft tissue) and prostate cancer clinical trials working group 3 (PCWG3) (bone), or death from any cause, whichever occurred first. The radiographic PD for soft tissue lesion was determined based on computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria and no confirmatory scan was required for soft tissue PD; for bone lesion was determined by 2 or more new bone lesions on bone scan per PCWG3 criteria (i.e., the appearance of 2 or more new bone lesions on bone scan) and the 2 scans (i.e., the confirmatory scan is required for bone disease progression) should be at least 6 weeks apart from each other.
Assessments performed at screening (within 4 weeks of randomization) and every 8 weeks for first 6 months and then every 12 weeks thereafter, until death, PD, unacceptable toxicity, consent withdrawal, or termination of study. Approximately 200 weeks
Secondary Outcomes (20)
Phase 1b and 2: Percentage of Participants With Confirmed Prostate-Specific Antigen >=50% (PSA50) Response
From Cycle 1 Day 1 (Baseline) up to either 30 days after last dose of study drug or until initiation of subsequent anticancer therapy or end of treatment visit. Assessed up to 149 weeks and 191 weeks for Phase 1b and Phase 2 respectively
Phase 1b and 2: Objective Response Rate (ORR)
Tumor assessments performed at screening (within 4 weeks of randomization) and every 8 weeks for first 6 months and then every 12 weeks thereafter, until death, PD, unacceptable toxicity, consent withdrawal, or termination of study.Approximately 259 weeks
Phase 1b and 2: Best Overall Response (BOR)
Tumor assessments performed at screening (within 4 weeks of randomization) and every 8 weeks for first 6 months and then every 12 weeks thereafter, until death, PD, unacceptable toxicity, consent withdrawal, or termination of study.Approximately 259 weeks
Phase 1b and 2: Disease Control Rate (DCR) at 6 Months
Baseline and at 6 months (24 weeks)
Phase 1b and 2: Time to First Skeletal-Related Event (SRE) Per Prostate Cancer Clinical Trials Working Group 3 Criteria
From first dose of study drug (Phase 1b) and randomization (Phase 2) (Day 1) up to approximately 259 weeks
- +15 more secondary outcomes
Study Arms (4)
Phase 1b: Tazemetostat in Combination with Abiraterone/Prednisone
EXPERIMENTALIn 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
Phase 1b: Tazemetostat in Combination with Enzalutamide
EXPERIMENTALIn 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
Phase 2: Tazemetostat in Combination with Enzalutamide
EXPERIMENTALParticipants 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.
Phase 2: Enzalutamide only
ACTIVE COMPARATORIn Phase 2, Enzalutamide will be administered on cycle 1 day 1
Interventions
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.
Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene
enzalutamide 160 mg (four 40 mg capsules) orally once daily
Eligibility Criteria
You may qualify if:
- Age at the time of consent ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (Appendix
- Life expectancy of \> 3 months.
- Histologically or cytologically confirmed adenocarcinoma of the prostate. Small cell or neuroendocrine tumors of the prostate are also permitted.
- 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.
- 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.
- 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.
You may not qualify if:
- Known symptomatic brain metastases
- 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.
- alpha-reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol), or progesterones within 2 weeks.
- 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.
- Severe concurrent disease, infection, or comorbidity that, in the judgment of the Investigator, would make the subject inappropriate for enrollment
- Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Epizyme, Inc.lead
Study Sites (24)
Genesis Healthcare Partners
San Diego, California, 92123, United States
The Urology Center Of Colorado
Denver, Colorado, 80211, United States
Hematology Oncology Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952, United States
XCancer - Northwest Oncology and Hematology
Rolling Meadows, Illinois, 60008, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Comprehensive Cancer Centers of Nevada - Central Valley
Las Vegas, Nevada, 89169, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Associated Medical Professionals of NY, PLLC - Urology
Syracuse, New York, 13210, United States
Montefiore Einstein Center for Cancer Care
The Bronx, New York, 10461, United States
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
SCRI - Tennessee Oncology Chattanooga
Chattanooga, Tennessee, 37404, United States
Urology Associates P.C.
Hendersonville, Tennessee, 37075, United States
XCancer - Tennesee Cancer Specialists
Knoxville, Tennessee, 37909, United States
SCRI - Tennessee Oncology Nashville
Nashville, Tennessee, 37203, United States
Urology San Antonio
San Antonio, Texas, 78229, United States
Academisch Ziekenhuis Groeninge Campus Kennedylaan
Kortrijk, West Vlaanderen, Belgium
Hospital Universitario de Jerez de la Frontera
Jerez de la Frontera, Cadiz, Spain
Hospital de la Santa Creu i. Sant Pau
Barcelona, Spain
Hospital del Mar Parc de Salut Mar
Barcelona, Spain
Hospital Clinico San Carlos
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Clinica Universidad de Navarra
Pamplona, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study was terminated early as Sponsor decided to discontinue the development of tazemetostat in mCRPC and the primary endpoint was not met for this study. There were no safety concerns.
Results Point of Contact
- Title
- Medical Director
- Organization
- Ipsen
Study Officials
- STUDY DIRECTOR
Ipsen Medical Director
Ipsen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 14, 2019
First Posted
November 27, 2019
Study Start
November 18, 2019
Primary Completion
November 4, 2024
Study Completion
November 4, 2024
Last Updated
March 10, 2026
Results First Posted
March 10, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
- Access Criteria
- Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.