Back to resultsA Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer (CELLO-1)
Primary Purpose
Metastatic Prostate Cancer, Metastatic Castration-resistant Prostate Cancer
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Tazemetostat
Abiraterone/prednisone
Enzalutamide
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Prostate Cancer focused on measuring metastatic castration resistant prostate cancer, tazemetostat, EPZ-6438, E7438, enzalutamide, abiraterone, Prednisone, Zytiga, Xtandi
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 5-alpha-reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol), or progesterones within 2 weeks.
- Chemotherapy (except as permitted in inclusion criteria #10) within 3 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.
Sites / Locations
- Genesis Healthcare Partners
- The Urology Center Of Colorado
- Hematology Oncology Associates of the Treasure Coast
- XCancer - Northwest Oncology and Hematology
- Dana Farber Cancer Institute
- Beth Israel Deaconess Medical Center
- Comprehensive Cancer Centers of Nevada - Central Valley
- Montefiore Einstein Center for Cancer Care
- Memorial Sloan Kettering Cancer Center
- Associated Medical Professionals of NY, PLLC - Urology
- University of Pittsburgh Medical Center - Hillman Cancer Center
- SCRI - Tennessee Oncology Chattanooga
- Urology Associates P.C.
- XCancer - Tennesee Cancer Specialists
- SCRI - Tennessee Oncology Nashville
- Urology San Antonio
- Academisch Ziekenhuis Groeninge Campus Kennedylaan
- Hospital Universitario de Jerez de la Frontera
- Hospital de la Santa Creu i. Sant Pau
- Hospital del Mar Parc de Salut Mar
- Hospital Clinico San Carlos
- Hospital Universitario 12 de Octubre
- Hospital Universitario La Paz
- Clinica Universidad de Navarra
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
Phase 1b: Tazemetostat in Combination with Abiraterone/Prednisone
Phase 1b: Tazemetostat in Combination with Enzalutamide
Phase 2: Tazemetostat in Combination with Enzalutamide
Phase 2: Enzalutamide only
Arm Description
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
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
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.
In Phase 2, Enzalutamide will be administered on cycle 1 day 1
Outcomes
Primary Outcome Measures
Ph 1b: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)
An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Ph 1b: Select the recommended phase 2 doses (RP2D) of tazemetostat for each combination
Based on pharmacokinetic (PK) and pharmacodynamic parameters as well as efficacy and the overall tolerability of each of the combinations (tazemetost with enzalutamide or tazemetostat with abiraterone/prednisone)
Ph 2: Change in radiographic progression free survival (rPFS)
Assessed by change radiographic progression free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria for progression in bone or in soft tissue
Secondary Outcome Measures
Phase 1b and 2: Percentage of participants with a ≥50% decline of Prostate Specific-Antigen (PSA50).
For participants with a baseline PSA ≥2.0 ug/L (ng/mL) per PCWG3 criteria
Phase 1b and 2: Objective response rate (ORR) and best overall response (BOR) in soft tissue
According to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines.
Phase 1b and 2: Disease control rate (DCR)
Assessed by radiographic progression per PCWG3 criteria, with no unequivocal clinical progression or death
Phase 1b and 2: Time to first skeletal-related event (SRE)
Phase 1b and 2: Time to initiation of the next systemic treatment for prostate cancer (TTNT)
TTNT is defined as the time from the date of randomization to date of first documented administration of the next systemic treatment for prostate cancer.
Phase 1b and 2: Time to PSA progression (TTPP)
Defined as the duration per PCWG3 criteria in months.
Phase 1b and 2: Reduction in circulating tumor cells (CTC)
From a state of having a detectable number of CTCs to having an undetectable number of CTCs
Phase 1b and 2: CTC response rate
Defined as the percentage of participants with a ≥30% reduction in CTC number
Phase 1b and Phase 2: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Phase 1b and 2: AUC0-last: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Phase 1b and 2:AUC0-24: area under the plasma concentration-time curve from time 0 to the time of 24 hours.
AUC_0-24 is defined as the concentration of drug over time from time zero to 24 hours.
Phase 1b and 2: Cmax: maximum plasma concentration.
Cmax is defined as the maximum observed concentration of drug.
Phase 2: Change in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Assessed by Well-being Subscale (FWB) and Prostate Cancer Subscale (PCS) scores
Phase 2: Time to definitive deterioration (TDD) in functional status and in prostate symptoms
Assessed by the FACT-P FWB and PCS scores.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04179864
Brief Title
A Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer
Acronym
CELLO-1
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 18, 2019 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Epizyme, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Prostate Cancer, Metastatic Castration-resistant Prostate Cancer
Keywords
metastatic castration resistant prostate cancer, tazemetostat, EPZ-6438, E7438, enzalutamide, abiraterone, Prednisone, Zytiga, Xtandi
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
104 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 1b: Tazemetostat in Combination with Abiraterone/Prednisone
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 1b: Tazemetostat in Combination with Enzalutamide
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 2: Tazemetostat in Combination with Enzalutamide
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2: Enzalutamide only
Arm Type
Active Comparator
Arm Description
In Phase 2, Enzalutamide will be administered on cycle 1 day 1
Intervention Type
Drug
Intervention Name(s)
Tazemetostat
Other Intervention Name(s)
EPZ-6438, E7438, IPN60200
Intervention Description
Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene
Intervention Type
Drug
Intervention Name(s)
Abiraterone/prednisone
Other Intervention Name(s)
Zytiga
Intervention Description
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
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
Xtandi
Intervention Description
enzalutamide 160 mg (four 40 mg capsules) orally once daily
Primary Outcome Measure Information:
Title
Ph 1b: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)
Description
An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time Frame
At end of Cycle 1 (each cycle is 28 days)
Title
Ph 1b: Select the recommended phase 2 doses (RP2D) of tazemetostat for each combination
Description
Based on pharmacokinetic (PK) and pharmacodynamic parameters as well as efficacy and the overall tolerability of each of the combinations (tazemetost with enzalutamide or tazemetostat with abiraterone/prednisone)
Time Frame
1 cycle/28 days
Title
Ph 2: Change in radiographic progression free survival (rPFS)
Description
Assessed by change radiographic progression free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria for progression in bone or in soft tissue
Time Frame
Day 1 of Cycles 3, 5, 7, 10, and 13, and every 12 weeks after Cycle 13 for 1 year (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Phase 1b and 2: Percentage of participants with a ≥50% decline of Prostate Specific-Antigen (PSA50).
Description
For participants with a baseline PSA ≥2.0 ug/L (ng/mL) per PCWG3 criteria
Time Frame
From baseline at any time on study, an average of one year
Title
Phase 1b and 2: Objective response rate (ORR) and best overall response (BOR) in soft tissue
Description
According to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines.
Time Frame
At 6 months on treatment.
Title
Phase 1b and 2: Disease control rate (DCR)
Description
Assessed by radiographic progression per PCWG3 criteria, with no unequivocal clinical progression or death
Time Frame
At 6 months on treatment.
Title
Phase 1b and 2: Time to first skeletal-related event (SRE)
Time Frame
During screening and every 9 weeks if clinically indicated at baseline, average of one year
Title
Phase 1b and 2: Time to initiation of the next systemic treatment for prostate cancer (TTNT)
Description
TTNT is defined as the time from the date of randomization to date of first documented administration of the next systemic treatment for prostate cancer.
Time Frame
From baseline to end of study, an average of one year
Title
Phase 1b and 2: Time to PSA progression (TTPP)
Description
Defined as the duration per PCWG3 criteria in months.
Time Frame
From baseline to the day of PSA progression, an average one one year.
Title
Phase 1b and 2: Reduction in circulating tumor cells (CTC)
Description
From a state of having a detectable number of CTCs to having an undetectable number of CTCs
Time Frame
From screening to 30 days after last dose
Title
Phase 1b and 2: CTC response rate
Description
Defined as the percentage of participants with a ≥30% reduction in CTC number
Time Frame
From baseline to end of study, an average of one year
Title
Phase 1b and Phase 2: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time Frame
From baseline to end of study, an average of one year
Title
Phase 1b and 2: AUC0-last: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
Description
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time Frame
From baseline to end of study, an average of one year
Title
Phase 1b and 2:AUC0-24: area under the plasma concentration-time curve from time 0 to the time of 24 hours.
Description
AUC_0-24 is defined as the concentration of drug over time from time zero to 24 hours.
Time Frame
From baseline to end of study, an average of one year
Title
Phase 1b and 2: Cmax: maximum plasma concentration.
Description
Cmax is defined as the maximum observed concentration of drug.
Time Frame
From baseline to end of study, an average of one year
Title
Phase 2: Change in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Description
Assessed by Well-being Subscale (FWB) and Prostate Cancer Subscale (PCS) scores
Time Frame
From baseline to end of study, an average of one year
Title
Phase 2: Time to definitive deterioration (TDD) in functional status and in prostate symptoms
Description
Assessed by the FACT-P FWB and PCS scores.
Time Frame
From baseline to end of study, an average of one year
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
5-alpha-reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol), or progesterones within 2 weeks.
Chemotherapy (except as permitted in inclusion criteria #10) within 3 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ipsen Medical Director
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
Facility Name
Genesis Healthcare Partners
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
The Urology Center Of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80211
Country
United States
Facility Name
Hematology Oncology Associates of the Treasure Coast
City
Port Saint Lucie
State/Province
Florida
ZIP/Postal Code
34952
Country
United States
Facility Name
XCancer - Northwest Oncology and Hematology
City
Rolling Meadows
State/Province
Illinois
ZIP/Postal Code
60008
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada - Central Valley
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Montefiore Einstein Center for Cancer Care
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Associated Medical Professionals of NY, PLLC - Urology
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
University of Pittsburgh Medical Center - Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
SCRI - Tennessee Oncology Chattanooga
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Urology Associates P.C.
City
Hendersonville
State/Province
Tennessee
ZIP/Postal Code
37075
Country
United States
Facility Name
XCancer - Tennesee Cancer Specialists
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
Facility Name
SCRI - Tennessee Oncology Nashville
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Urology San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Academisch Ziekenhuis Groeninge Campus Kennedylaan
City
Kortrijk
State/Province
West Vlaanderen
Country
Belgium
Facility Name
Hospital Universitario de Jerez de la Frontera
City
Jerez De La Frontera
State/Province
Cadiz
Country
Spain
Facility Name
Hospital de la Santa Creu i. Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital del Mar Parc de Salut Mar
City
Barcelona
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Facility Name
Clinica Universidad de Navarra
City
Pamplona
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
A Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer
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