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 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%.
Outcome Measure
Phase 1b: Number of Participants With Treatment-Emergent Non-Serious Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs)
Outcome Time Frame
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
Outcome Description
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).
Outcome Measure
Phase 1b: Recommended Phase 2 Dose (RP2D) of Tazemetostat
Outcome Time Frame
From Day 1 up to Day 28 of Cycle 1 (each cycle was 28 days)
Outcome Description
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.
Outcome Measure
Phase 2: Radiographic Progression-Free Survival (rPFS)
Outcome Time Frame
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 Ids
Secondary Id
2019-003649-14
Secondary Outcomes
Outcome Description
Blood samples were collected for evaluation of PSA. Confirmed PSA50 response was defined as \>=50% decline of PSA from baseline at any time on study for participants with a baseline PSA \>=1.0 microgram per liter (mcg/L) (nanogram/milliliter \[ng/mL\]) per PCWG3 criteria. Baseline was defined as: Phase 1b: last value recorded for a variable prior to or on the date the participant received the first dose of study drug; Phase 2: last value recorded for a variable prior to or on the date of randomization.
Outcome Time Frame
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
Outcome Measure
Phase 1b and 2: Percentage of Participants With Confirmed Prostate-Specific Antigen >=50% (PSA50) Response
Outcome Description
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR). CR was defined as disappearance of all target lesions, any pathological lymph nodes (LN) must be \<10 millimeter (mm) in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
Outcome Time Frame
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
Outcome Measure
Phase 1b and 2: Objective Response Rate (ORR)
Outcome Description
BOR was defined as percentage of participants with CR, PR, stable disease (SD), PD, or not evaluable (NE). CR was defined as disappearance of all target lesions, any pathological LN must be \<10 mm in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the drug started. In addition, the sum had an absolute increase from nadir of 5 mm. NE was defined as which cannot be classified by 1 of the above preceding definitions. Percentages are rounded off to the tenth decimal place.
Outcome Time Frame
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
Outcome Measure
Phase 1b and 2: Best Overall Response (BOR)
Outcome Description
DCR at 6 months (24 weeks) was defined as percentage of participants with measurable soft tissue disease at baseline who had BOR of CR or PR and remaining on study without progression at 23 weeks or with a duration of SD for at least 23 weeks after of randomization (phase 2)/first dose (phase 1b) using overall imaging-based response assessed by RECIST 1.1 (soft tissue) and PCWG-3 criteria (bone). BOR: percentage of participants with CR, PR, SD, PD, or NE. CR: disappearance of all target lesions, any pathological LN must be \<10 mm in the short axis. PR: at least a 30% decrease in sum of diameters of target lesions, taking as a reference, baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: at least a 20% increase in sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since the drug started. In addition, sum had an absolute increase from nadir of 5 mm.
Outcome Time Frame
Baseline and at 6 months (24 weeks)
Outcome Measure
Phase 1b and 2: Disease Control Rate (DCR) at 6 Months
Outcome Description
Time to first SRE per PCWG3 criteria was defined as the time from the date of randomization (phase II)/date of the first dose of study drug (phase Ib) to the date of first SRE. An SRE was defined as radiation therapy or surgery to bone, pathologic bone fracture, or spinal cord compression.
Outcome Time Frame
From first dose of study drug (Phase 1b) and randomization (Phase 2) (Day 1) up to approximately 259 weeks
Outcome Measure
Phase 1b and 2: Time to First Skeletal-Related Event (SRE) Per Prostate Cancer Clinical Trials Working Group 3 Criteria
Outcome Description
TTNT was defined as the time from the date of randomization (phase II)/date of the first dose of the study drug (phase Ib) to the date of the first documented administration of systemic treatment for prostate cancer.
Outcome Time Frame
From first dose of study drug (Phase 1b) and randomization (Phase 2) (Day 1) up to approximately 259 weeks
Outcome Measure
Phase 1b and 2: Time to Initiation of the Next Systemic Treatment (TTNT) for Prostate Cancer
Outcome Description
TTPP was defined as the duration from the date of randomization (phase II)/date of first dose of study drug (phase Ib) to the date of first PSA progression per PCWG3 criteria. PSA progression was defined as a \>=25% increase and an absolute increase of \>=2 mcg/L (2 ng/mL) above the nadir (or baseline value for participants who did not have a decline in PSA value beyond 12 weeks). Baseline was defined as: Phase 1b: last value recorded for a variable prior to or on the date the participant received the first dose of study drug; Phase 2: last value recorded for a variable prior to or on the date of randomization.
Outcome Time Frame
From first dose of study drug (Phase 1b) and randomization (Phase 2) (Day 1) up to approximately 259 weeks
Outcome Measure
Phase 1b and 2: Time to Prostate-Specific Antigen Progression (TTPP)
Outcome Description
Blood samples were collected for evaluation of CTC. Reduction in CTC was defined as participants from a state of having a detectable number of CTCs to having an undetectable number of CTCs. Percentage of participants with detectable CTC at baseline and non-detectable CTC are presented. Baseline was defined as: Phase 1b: last value recorded for a variable prior to or on the date the participant received the first dose of study drug; Phase 2: last value recorded for a variable prior to or on the date of randomization. Percentage of participants with detectable CTC at baseline and non-detectable CTC at any post-baseline time point up to 149 weeks and 191 weeks for Phase 1b and Phase 2 respectively are presented.
Outcome Time Frame
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
Outcome Measure
Phase 1b and 2: Percentage of Participants With Reduction in Circulating Tumor Cells (CTC)
Outcome Description
Blood samples were collected for evaluation of CTC. CTC response was defined as a \>=30% reduction in CTC number from baseline in participants who entered the study. Baseline was defined as: Phase 1b: last value recorded for a variable prior to or on the date the participant received the first dose of study drug; Phase 2: last value recorded for a variable prior to or on the date of randomization.
Outcome Time Frame
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
Outcome Measure
Phase 1b and 2: Percentage of Participants With Circulating Tumor Cells Response
Outcome Description
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 the 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 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%.
Outcome Time Frame
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 191 weeks
Outcome Measure
Phase 2: Number of Participants With Treatment-Emergent Non-Serious Adverse Events and Treatment-Emergent Serious Adverse Events
Outcome Description
Blood samples were collected at specified timepoints for the assessment of AUC0-last of tazemetostat.
Outcome Time Frame
Cycle 1 Days 2 and 21 (each cycle was 28 days)
Outcome Measure
Phase 1b: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Tazemetostat
Outcome Description
Blood samples were collected at specified timepoints for the assessment of Cmax of tazemetostat.
Outcome Time Frame
Cycle 1 Days 2 and 21 (each cycle was 28 days)
Outcome Measure
Phase 1b: Maximum Plasma Concentration (Cmax) of Tazemetostat
Outcome Description
Blood samples were collected at specified timepoints for the assessment of AUC0-8 of tazemetostat.
Outcome Time Frame
Up to 8 hours post-dose on Cycle 1 Days 2 and 21 (each cycle was 28 days)
Outcome Measure
Phase 1b: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of 8 Hours Post-Dose (AUC0-8) of Tazemetostat
Outcome Description
Blood samples were collected at specified timepoints for the assessment of AUC0-12 of tazemetostat.
Outcome Time Frame
Up to 12 hours post-dose on Cycle 1 Days 2 and 21 (each cycle was 28 days)
Outcome Measure
Phase 1b: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of 12 Hours Post-Dose (AUC0-12) of Tazemetostat
Outcome Description
Blood samples were collected at specified timepoints for the assessment of AUC0-24 of enzalutamide.
Outcome Time Frame
Up to 24 hours post-dose on Cycle 1 Days 1, 2 and 21 (each cycle was 28 days)
Outcome Measure
Phase 1b: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of 24 Hours Post-Dose (AUC0-24) of Enzalutamide
Outcome Description
For Phase 2, PK blood samples for assessment of Cmax of enzalutamide were pre-specified to be collected at different time points by treatment arm. In the Phase 2: Tazemetostat 1200 mg + Enzalutamide arm, samples were collected at Cycle 1 Days 2 and 21 only. In the Phase 2: Enzalutamide arm, samples were collected at Cycle 1 Day 1 only. No PK samples were collected at other time points for these arms.
Outcome Time Frame
Cycle 1 Days 2 and 21 for Phase 2: Tazemetostat 1200 mg + Enzalutamide arm and Cycle 1 Day 1 for Phase 2: Enzalutamide arm (each cycle was 28 days)
Outcome Measure
Phase 2: Maximum Plasma Concentration of Enzalutamide
Outcome Description
For Phase 2, PK blood samples for assessment of AUC0-last of enzalutamide were pre-specified to be collected at different time points by treatment arm. In the Phase 2: Tazemetostat 1200 mg + Enzalutamide arm, samples were collected at Cycle 1 Days 2 and 21 only. In the Phase 2: Enzalutamide arm, samples were collected at Cycle 1 Day 1 only. No PK samples were collected at other time points for these arms.
Outcome Time Frame
Cycle 1 Days 2 and 21 for Phase 2: Tazemetostat 1200 mg + Enzalutamide arm and Cycle 1 Day 1 for Phase 2: Enzalutamide arm (each cycle was 28 days)
Outcome Measure
Phase 2: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration of Enzalutamide
Outcome Description
For Phase 2, PK blood samples for assessment of enzalutamide AUC0-24 were pre-specified to be collected at different time points by treatment arm. In the Phase 2: Tazemetostat 1200 mg + Enzalutamide arm, samples were collected at Cycle 1 Days 2 and 21 only. In the Phase 2: Enzalutamide arm, samples were collected at Cycle 1 Day 1 only. No PK samples were collected at other time points for these arms.
Outcome Time Frame
Up to 24 hours post-dose on Cycle 1 Days 2 and 21 for Phase 2: Tazemetostat 1200 mg + Enzalutamide arm and up to 24 hours post-dose on Cycle 1 Day 1 for Phase 2: Enzalutamide arm (each cycle was 28 days)
Outcome Measure
Phase 2: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of 24 Hours Post-Dose of Enzalutamide
Outcome Description
FACT-P questionnaire included subscales:physical well-being(PWB) (Questions \[Q\] GP1 to GP7),social/family well-being subscale(SWB) (Q GS1 to GS7),emotional well-being subscale(EWB) (Q GE1 to GE6),functional well-being subscale(FWB) (Q GF1 to GF7) and prostate cancer subscale(PCS) (Q C2, C6, P1 to P8, BL2 and BL5). Each question had 5 responses, 0: "not at all", 1: "a little bit", 2: "somewhat", 3: "quite a bit" and 4: "very much". Scores ranged from 0 ("not at all") to 4 ("very much") for positively phrased questions. Negatively phrased questions had a reverse scoring, from 0 ("very much") to 4 ("not at all"). Q that were reversed (via subtraction of the response from 4) were: GP1-7, GE1, GE3-6, C2, P1-3, P6-P8 and BL2. Total FACT-P score was sum of scores of all sub-scales (PWB, SWB, EWB, FWB and PCS). Higher scores: better quality of life. Baseline: last value recorded for a variable prior to or on date of randomization. Change from baseline in FWB and PCS scores is presented.
Outcome Time Frame
Baseline (Day 1), Cycle (C) 3 Day 57, C 5 Day 113, C 7 Day 169, C 10 Day 253, C 13 Day 337, C 14 Day 421, C 15 Day 505, C 16 Day 589, C 17 Day 673, C 18 Day 757, C 19 Day 841, C 20 Day 925, C 21 Day 1009, C 22 Day 1093, C 23 Day 1177 and C 24 Day 1261
Outcome Measure
Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Prostrate (FACT-P): Functional Well-being Subscale (FWB) and Prostate Cancer Subscale (PCS) Scores
Outcome Description
TTD was defined as the interval from date of randomization until date of first clinically meaningful deterioration (3 points or more decline for subscale score, 10 points or more decline for total score) that was confirmed at subsequent visit at least 3 weeks apart with no improvement in between visits or death (by any cause) in absence of a clinically meaningful deterioration, regardless of whether participant discontinued study drug(s) prior to deterioration. PCS included Q C2, C6, P1 to P8, BL2 and BL5. Each question had 5 responses,0: "not at all",1: "a little bit",2: "somewhat",3: "quite a bit" and 4: "very much". Scores ranged from 0 ("not at all") to 4 ("very much") for positively phrased questions. Negatively phrased questions had a reverse scoring, from 0 ("very much") to 4 ("not at all"). Total FACT-P: sum of scores of all sub-scales(PWB, SWB, EWB, FWB and PCS). Higher scores: better quality of life. TDD in prostate symptoms as assessed by FACT-P: PCS score is presented.
Outcome Time Frame
Baseline (Day 1) up to Cycle 24 Day 1261
Outcome Measure
Phase 2: Time to Definitive Deterioration (TDD) in Prostate Symptoms as Assessed by the Functional Assessment of Cancer Therapy-Prostrate: Prostate Cancer Subscale Score
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