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.
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.
Brief Title
A Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer
Categories
Completion Date
Completion Date Type
Actual
Conditions
Metastatic Prostate Cancer
Metastatic Castration-resistant Prostate Cancer
Eligibility Criteria
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.
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.
* 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.
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.
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.
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.
* 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.
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.
Inclusion Criteria
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.
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.
Gender
Male
Gender Based
false
Keywords
metastatic castration resistant prostate cancer
tazemetostat
EPZ-6438
E7438
enzalutamide
abiraterone
Prednisone
Zytiga
Xtandi
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04179864
Org Class
Industry
Org Full Name
Ipsen
Org Study Id
EZH-1101
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome 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.
Outcome Measure
Ph 1b: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)
Outcome Time Frame
At end of Cycle 1 (each cycle is 28 days)
Outcome 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)
Outcome Measure
Ph 1b: Select the recommended phase 2 doses (RP2D) of tazemetostat for each combination
Outcome Time Frame
1 cycle/28 days
Outcome 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
Outcome Measure
Ph 2: Change in radiographic progression free survival (rPFS)
Outcome 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 Ids
Secondary Id
2019-003649-14
Secondary Outcomes
Outcome Description
For participants with a baseline PSA ≥2.0 ug/L (ng/mL) per PCWG3 criteria
Outcome Time Frame
From baseline at any time on study, an average of one year
Outcome Measure
Phase 1b and 2: Percentage of participants with a ≥50% decline of Prostate Specific-Antigen (PSA50).
Outcome Description
According to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines.
Outcome Time Frame
At 6 months on treatment.
Outcome Measure
Phase 1b and 2: Objective response rate (ORR) and best overall response (BOR) in soft tissue
Outcome Description
Assessed by radiographic progression per PCWG3 criteria, with no unequivocal clinical progression or death
Outcome Time Frame
At 6 months on treatment.
Outcome Measure
Phase 1b and 2: Disease control rate (DCR)
Outcome Time Frame
During screening and every 9 weeks if clinically indicated at baseline, average of one year
Outcome Measure
Phase 1b and 2: Time to first skeletal-related event (SRE)
Outcome 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.
Outcome Time Frame
From baseline to end of study, an average of one year
Outcome Measure
Phase 1b and 2: Time to initiation of the next systemic treatment for prostate cancer (TTNT)
Outcome Description
Defined as the duration per PCWG3 criteria in months.
Outcome Time Frame
From baseline to the day of PSA progression, an average one one year.
Outcome Measure
Phase 1b and 2: Time to PSA progression (TTPP)
Outcome Description
From a state of having a detectable number of CTCs to having an undetectable number of CTCs
Outcome Time Frame
From screening to 30 days after last dose
Outcome Measure
Phase 1b and 2: Reduction in circulating tumor cells (CTC)
Outcome Description
Defined as the percentage of participants with a ≥30% reduction in CTC number
Outcome Time Frame
From baseline to end of study, an average of one year
Outcome Measure
Phase 1b and 2: CTC response rate
Outcome 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.
Outcome Time Frame
From baseline to end of study, an average of one year
Outcome Measure
Phase 1b and Phase 2: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)
Outcome Description
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Outcome Time Frame
From baseline to end of study, an average of one year
Outcome Measure
Phase 1b and 2: AUC0-last: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
Outcome Description
AUC\_0-24 is defined as the concentration of drug over time from time zero to 24 hours.
Outcome Time Frame
From baseline to end of study, an average of one year
Outcome Measure
Phase 1b and 2:AUC0-24: area under the plasma concentration-time curve from time 0 to the time of 24 hours.
Outcome Description
Cmax is defined as the maximum observed concentration of drug.
Outcome Time Frame
From baseline to end of study, an average of one year
Outcome Measure
Phase 1b and 2: Cmax: maximum plasma concentration.
Outcome Description
Assessed by Well-being Subscale (FWB) and Prostate Cancer Subscale (PCS) scores
Outcome Time Frame
From baseline to end of study, an average of one year
Outcome Measure
Phase 2: Change in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Outcome Description
Assessed by the FACT-P FWB and PCS scores.
Outcome Time Frame
From baseline to end of study, an average of one year
Outcome Measure
Phase 2: Time to definitive deterioration (TDD) in functional status and in prostate symptoms
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Anna Ferrari
Investigator Email
aferrari@montefiore.org
Categories Mesh Debug
Prostate Cancer --- PROSTATIC NEOPLASMS
Prostate Cancer --- GENITAL NEOPLASMS, MALE
Prostate Cancer --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Prostate Cancer --- PROSTATIC DISEASES
MeSH Terms
PROSTATIC NEOPLASMS
GENITAL NEOPLASMS, MALE
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
GENITAL DISEASES, MALE
GENITAL DISEASES
UROGENITAL DISEASES
PROSTATIC DISEASES
MALE UROGENITAL DISEASES
TAZEMETOSTAT
ABIRATERONE
PREDNISONE
ABIRATERONE ACETATE
ENZALUTAMIDE
PREGNADIENEDIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
ANDROSTENES
ANDROSTANES