Clinical Trials List
Protocol NumberCO39385
NCT Number(ClinicalTrials.gov Identfier)NCT03016312
Completed
2017-02-01 - 2021-12-27
Phase III
Terminated4
ICD-10C61
Malignant neoplasm of prostate
A PHASE III, MULTICENTER, RANDOMIZED STUDY OF ATEZOLIZUMAB (ANTI−PD-L1 ANTIBODY) IN COMBINATION WITH ENZALUTAMIDE VERSUS ENZALUTAMIDE ALONE IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER AFTER FAILURE OF AN ANDROGEN SYNTHESIS INHIBITOR AND FAILURE OF, INELIGIBILITY FOR, OR REFUSAL OF A TAXANE REGIMEN
-
Trial Applicant
-
Sponsor
Hoffmann-La Roche
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 朱力行 Division of Nuclear Medicine
- Yi-Hsiu Huang Division of Urology
- 潘競成 Division of General Surgery
- Yen-Hwa Chang Division of Urology
- 沈書慧 Division of Radiology
- Tzu-chun Wei Division of Urology
- Tzu-Ping Lin Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 熊小澐 Division of Radiology
- 裘坤元 Division of Urology
- Jian-Ri Li Division of Urology
- Chuan-Shu Chen Division of Urology
- 蔡世傳 Division of Nuclear Medicine
- Cheng-Kuang Yang Division of Urology
- Cheng-Che Chen Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Linkou Chang Gung Medical Foundation
Taiwan National PI
林永昌
Co-Principal Investigator
- Rita cheng Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- See-Tong Pang Division of Hematology & Oncology
- 黃成之 Division of Radiology
- 劉忠一 Division of Hematology & Oncology
- 張英勛 Division of Hematology & Oncology
- Feng-Yuan Liu Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
7 Terminated
Audit
None
Co-Principal Investigator
- - - Division of Urology
- Ying-Chun Shen Division of Hematology & Oncology
- CHUNG-HSIN CHEN Division of Urology
- JHE-CYUAN GUO Division of Hematology & Oncology
- Yu-Chieh Tsai Division of Hematology & Oncology
- CHING-CHU LU Division of Nuclear Medicine
- YU-CHUAN LU Division of Urology
- YEN-HENG LIN Division of Radiology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Prostatic Neoplasms, Castration-Resistant
Objectives
This is a Phase III, multicenter, randomized open-label study designed to evaluate the
efficacy and safety of atezolizumab in combination with enzalutamide compared with
enzalutamide alone in patients with mCRPC after failure of an androgen synthesis
inhibitor and failure of, ineligibility for, or refusal of a taxane regimen.
Primary Efficacy Objective
• To evaluate the efficacy of atezolizumab/enzalutamide compared with enzalutamide alone
Test Drug
Atezolizumab
Active Ingredient
Atezolizumab
Dosage Form
IVT
Dosage
1200mg/20mL
Endpoints
Primary Outcome Measures :
Overall Survival (OS) [ Time Frame: Baseline until death from any cause (up to approximately 42 months) ]
Overall Survival is defined as the time from randomization to death from any cause.
Secondary Outcome Measures :
Percentage of Participants Who Survived at Month 12 and 24 [ Time Frame: Months 12, 24 ]
OS (Overall Survival is defined as the time from randomization to death from any cause) probability at 12 and 24 months
Time to First Symptomatic Skeletal Event (SSE) [ Time Frame: Baseline up to end of study (up to approximately 42 months) ]
An SSE is defined as external beam radiation therapy to relieve skeletal symptoms (including initiation of radium-223 dichloride or other types of radionuclide therapy to treat symptoms of bone metastases), new symptomatic pathologic bone fracture, clinically apparent occurrence of spinal cord compression, or tumor related orthopedic surgical intervention.
Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria [ Time Frame: Baseline until disease progression or death from any cause (up to approximately 42 months) ]
rPFS is defined as the time from randomization to the earliest occurrence of one of the following:
A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented.
Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1
Death from any cause
Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria [ Time Frame: Months 6, 12 ]
rPFS is defined as the time from randomization to the earliest occurrence of one of the following:
A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented.
Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1
Death from any cause
Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline [ Time Frame: Baseline until disease progression (up to approximately 42 months) ]
PSA response rate, defined as a > 50% decrease in PSA from baseline that is confirmed after ≥ 3 weeks by a consecutive confirmatory PSA measurement
Time to PSA Progression, Assessed as Per PCWG3 Criteria [ Time Frame: Baseline until disease progression (up to approximately 42 months) ]
In participants with no PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the baseline value, ≥12 weeks after baseline. In participants with an initial PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥3 weeks later.
Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria [ Time Frame: Baseline until disease progression or death from any cause (up to approximately 42 months) ]
Objective response rate in soft tissue lesions, defined as the percentage of participants with either a CR or PR on two consecutive occasions ≥ 6 weeks apart, as determined by the investigator through use of PCWG3 criteria
Percentage of Participants With Adverse Events [ Time Frame: Baseline up to end of study (up to approximately 42 month ]
Verbatim description of adverse events will be coded to MedDRA preferred terms and graded according to NCI CTCAE v4.0.
Minimum Observed Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-infusion (0 hour[hr]) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); treatment discontinuation visit, 120 days after last dose (up to approximately 42 months) ]
Atezolizumab serum concentration data (minimum [Cmin]) will be reported and summarized for each cycle where collected as appropriate.
Maximum Observed Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); 0.5 hr post-infusion (infusion duration: 60 minutes [min]) on Day 1 Cycle 1; treatment discontinuation visit, 120 days after last dose (up to approximately 42 months) ]
Atezolizumab serum concentration data (maximum [Cmax]) will be reported and summarized for each cycle where collected as appropriate.
Plasma Concentration of Enzalutamide [ Time Frame: Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8 ]
Plasma concentrations of Enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.
Plasma Concentration of N-Desmethyl Enzalutamide [ Time Frame: Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8 ]
Plasma concentrations of N-desmethyl enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of atezolizumab; up to 42 months ]
The numbers and proportions of ATA-positive participants and ATA-negative participants at baseline (baseline prevalence) and after baseline (post-baseline incidence) will be summarized by treatment group.
Overall Survival (OS) [ Time Frame: Baseline until death from any cause (up to approximately 42 months) ]
Overall Survival is defined as the time from randomization to death from any cause.
Secondary Outcome Measures :
Percentage of Participants Who Survived at Month 12 and 24 [ Time Frame: Months 12, 24 ]
OS (Overall Survival is defined as the time from randomization to death from any cause) probability at 12 and 24 months
Time to First Symptomatic Skeletal Event (SSE) [ Time Frame: Baseline up to end of study (up to approximately 42 months) ]
An SSE is defined as external beam radiation therapy to relieve skeletal symptoms (including initiation of radium-223 dichloride or other types of radionuclide therapy to treat symptoms of bone metastases), new symptomatic pathologic bone fracture, clinically apparent occurrence of spinal cord compression, or tumor related orthopedic surgical intervention.
Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria [ Time Frame: Baseline until disease progression or death from any cause (up to approximately 42 months) ]
rPFS is defined as the time from randomization to the earliest occurrence of one of the following:
A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented.
Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1
Death from any cause
Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria [ Time Frame: Months 6, 12 ]
rPFS is defined as the time from randomization to the earliest occurrence of one of the following:
A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented.
Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1
Death from any cause
Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline [ Time Frame: Baseline until disease progression (up to approximately 42 months) ]
PSA response rate, defined as a > 50% decrease in PSA from baseline that is confirmed after ≥ 3 weeks by a consecutive confirmatory PSA measurement
Time to PSA Progression, Assessed as Per PCWG3 Criteria [ Time Frame: Baseline until disease progression (up to approximately 42 months) ]
In participants with no PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the baseline value, ≥12 weeks after baseline. In participants with an initial PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥3 weeks later.
Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria [ Time Frame: Baseline until disease progression or death from any cause (up to approximately 42 months) ]
Objective response rate in soft tissue lesions, defined as the percentage of participants with either a CR or PR on two consecutive occasions ≥ 6 weeks apart, as determined by the investigator through use of PCWG3 criteria
Percentage of Participants With Adverse Events [ Time Frame: Baseline up to end of study (up to approximately 42 month ]
Verbatim description of adverse events will be coded to MedDRA preferred terms and graded according to NCI CTCAE v4.0.
Minimum Observed Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-infusion (0 hour[hr]) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); treatment discontinuation visit, 120 days after last dose (up to approximately 42 months) ]
Atezolizumab serum concentration data (minimum [Cmin]) will be reported and summarized for each cycle where collected as appropriate.
Maximum Observed Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); 0.5 hr post-infusion (infusion duration: 60 minutes [min]) on Day 1 Cycle 1; treatment discontinuation visit, 120 days after last dose (up to approximately 42 months) ]
Atezolizumab serum concentration data (maximum [Cmax]) will be reported and summarized for each cycle where collected as appropriate.
Plasma Concentration of Enzalutamide [ Time Frame: Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8 ]
Plasma concentrations of Enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.
Plasma Concentration of N-Desmethyl Enzalutamide [ Time Frame: Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8 ]
Plasma concentrations of N-desmethyl enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of atezolizumab; up to 42 months ]
The numbers and proportions of ATA-positive participants and ATA-negative participants at baseline (baseline prevalence) and after baseline (post-baseline incidence) will be summarized by treatment group.
Inclution Criteria
Inclusion Criteria
Patients must meet the following criteria for study entry:
• Signed Informed Consent Form
• Age ≥ 18 years
• Ability to comply with the study protocol, in the investigator’s judgment
• ECOG performance status of 0 or 1
• Life expectancy ≥ 3 months
• Histologically confirmed adenocarcinoma of the prostate
Disease must be either metastatic or locally confined inoperable disease that
cannot be treated with definitive intent (no chance for a curative intervention)
Patients presenting with treatment emergent neuroendocrine differentiation, but
not primary small cell features, are eligible
• Known castrate-resistant disease, defined as meeting all of the following criteria:
Castrate serum testosterone level ≤ 50 ng/dL (1.7 nmol/L) at the screening visit
Bilateral orchiectomy or maintenance on androgen ablation therapy with
luteinizing hormone-releasing hormone agonist or antagonist or polyestradiol
phosphate for the duration of the study (including the follow-up period)
• Progressive disease prior to screening by PSA or imaging per PCWG3 criteria
during or following the direct prior line of therapy in the setting of medical or surgical
castration. Disease progression for study entry is defined as one or more of the
following three criteria:
PSA progression defined as two consecutive increases in PSA over a previous
reference value ≥1 ng/mL (μg/L), with each progression measurement at least
1 week apart
Soft tissue disease progression defined by RECIST v1.1
Previously normal (< 1.0 cm) lymph nodes must have grown by ≥ 5 mm in the
short axis to be considered to have progressed
Bone disease progression defined by two or more new lesions on bone scan
• One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or
ineligibility of a taxane-containing regimen
Patients who have received a taxane-containing regimen for hormone sensitive
prostate cancer are eligible. Patients must present with confirmed
castrate-resistant disease prior to study entry defined as progressive
radiographic disease on castrate levels of serum testosterone.
Patients who refuse or are ineligible for a taxane-containing regimen are eligible
for enrollment if they have no intention to use cytotoxic chemotherapy within the
next 6 months after an informed discussion.
A taxane-containing treatment should be considered in patients with
symptomatic and extensive visceral disease who have not previously received
and are good candidates for a taxane-containing regimen.
• One prior regimen/line of an androgen synthesis inhibitor for mCRPC
(e.g., abiraterone, orteronel or galeterone)
Patients must have received at least 28 days of an androgen synthesis inhibitor.
Prior treatment with first generation antiandrogens (e.g., nilutamide,
bicalutamide), oral ketoconazole, vaccines (e.g., sipuleucel-T, prostvac VF),
and radium-223 dichloride is allowed.
• Patients receiving bisphosphonate or denosumab therapy must have been on a
stable dose for at least 4 weeks.
• Availability of a representative tumor specimen from a site not previously irradiated
that is suitable for determination of PD-L1 status via central testing
A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block
(preferred) or at least 15 slides containing unstained, freshly cut, serial sections
must be submitted along with an associated pathology report prior to study
enrollment. If only 10−14 slides are available, the patient may still be eligible
for the study, after discussion with and approval by the Medical Monitor. If
archival tumor tissue is unavailable or is determined to be unsuitable for
required testing, tumor tissue must be obtained from a biopsy performed at
screening. No tissue will be collected for patients enrolled in the safety run-in
phase. Refer to Section 4.5.6 for additional information on tumor specimens
collected at screening.
• Adequate hematologic and end-organ function, defined by the following laboratory
test results, obtained within 14 days prior to initiation of study treatment:
ANC ≥ 1.5 ×109
/L (without granulocyte colony-stimulating factor support within
2 weeks prior to Cycle 1, Day 1)
Lymphocyte count ≥ 0.5× 109/L
Platelet count ≥ 100 × 109/L without transfusion
Hemoglobin ≥ 90 g/L
Patients may be transfused or receive erythropoietic treatment to meet this
criterion
AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 ×ULN, with the following
exceptions:
Patients with documented liver metastases: AST and ALT ≤ 5 ×ULN
Patients with documented liver or bone metastases: ALP ≤ 5 ×ULN
Serum bilirubin ≤ 1.5 ×ULN with the following exception:
Patients with known Gilbert disease: serum bilirubin level ≤ 3 ×ULN
Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula)
Serum albumin ≥ 2.5 g/dL
For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 ×ULN
within 14 days prior to initiation of study treatment
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• For men who are not surgically sterile: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures, and agreement to refrain
from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or
use a condom plus an additional contraceptive method that together result in a
failure rate of < 1% per year during the treatment period and for at least
3 months after the last dose of enzalutamide. Men must refrain from donating
sperm during this same period.
With pregnant female partners, men must remain abstinent or use a condom
during the treatment period and for 3 months after the last dose of
enzalutamide to avoid exposing the embryo.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical study and the preferred and usual lifestyle of the patient.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not acceptable methods of contraception.
Patients must meet the following criteria for study entry:
• Signed Informed Consent Form
• Age ≥ 18 years
• Ability to comply with the study protocol, in the investigator’s judgment
• ECOG performance status of 0 or 1
• Life expectancy ≥ 3 months
• Histologically confirmed adenocarcinoma of the prostate
Disease must be either metastatic or locally confined inoperable disease that
cannot be treated with definitive intent (no chance for a curative intervention)
Patients presenting with treatment emergent neuroendocrine differentiation, but
not primary small cell features, are eligible
• Known castrate-resistant disease, defined as meeting all of the following criteria:
Castrate serum testosterone level ≤ 50 ng/dL (1.7 nmol/L) at the screening visit
Bilateral orchiectomy or maintenance on androgen ablation therapy with
luteinizing hormone-releasing hormone agonist or antagonist or polyestradiol
phosphate for the duration of the study (including the follow-up period)
• Progressive disease prior to screening by PSA or imaging per PCWG3 criteria
during or following the direct prior line of therapy in the setting of medical or surgical
castration. Disease progression for study entry is defined as one or more of the
following three criteria:
PSA progression defined as two consecutive increases in PSA over a previous
reference value ≥1 ng/mL (μg/L), with each progression measurement at least
1 week apart
Soft tissue disease progression defined by RECIST v1.1
Previously normal (< 1.0 cm) lymph nodes must have grown by ≥ 5 mm in the
short axis to be considered to have progressed
Bone disease progression defined by two or more new lesions on bone scan
• One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or
ineligibility of a taxane-containing regimen
Patients who have received a taxane-containing regimen for hormone sensitive
prostate cancer are eligible. Patients must present with confirmed
castrate-resistant disease prior to study entry defined as progressive
radiographic disease on castrate levels of serum testosterone.
Patients who refuse or are ineligible for a taxane-containing regimen are eligible
for enrollment if they have no intention to use cytotoxic chemotherapy within the
next 6 months after an informed discussion.
A taxane-containing treatment should be considered in patients with
symptomatic and extensive visceral disease who have not previously received
and are good candidates for a taxane-containing regimen.
• One prior regimen/line of an androgen synthesis inhibitor for mCRPC
(e.g., abiraterone, orteronel or galeterone)
Patients must have received at least 28 days of an androgen synthesis inhibitor.
Prior treatment with first generation antiandrogens (e.g., nilutamide,
bicalutamide), oral ketoconazole, vaccines (e.g., sipuleucel-T, prostvac VF),
and radium-223 dichloride is allowed.
• Patients receiving bisphosphonate or denosumab therapy must have been on a
stable dose for at least 4 weeks.
• Availability of a representative tumor specimen from a site not previously irradiated
that is suitable for determination of PD-L1 status via central testing
A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block
(preferred) or at least 15 slides containing unstained, freshly cut, serial sections
must be submitted along with an associated pathology report prior to study
enrollment. If only 10−14 slides are available, the patient may still be eligible
for the study, after discussion with and approval by the Medical Monitor. If
archival tumor tissue is unavailable or is determined to be unsuitable for
required testing, tumor tissue must be obtained from a biopsy performed at
screening. No tissue will be collected for patients enrolled in the safety run-in
phase. Refer to Section 4.5.6 for additional information on tumor specimens
collected at screening.
• Adequate hematologic and end-organ function, defined by the following laboratory
test results, obtained within 14 days prior to initiation of study treatment:
ANC ≥ 1.5 ×109
/L (without granulocyte colony-stimulating factor support within
2 weeks prior to Cycle 1, Day 1)
Lymphocyte count ≥ 0.5× 109/L
Platelet count ≥ 100 × 109/L without transfusion
Hemoglobin ≥ 90 g/L
Patients may be transfused or receive erythropoietic treatment to meet this
criterion
AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 ×ULN, with the following
exceptions:
Patients with documented liver metastases: AST and ALT ≤ 5 ×ULN
Patients with documented liver or bone metastases: ALP ≤ 5 ×ULN
Serum bilirubin ≤ 1.5 ×ULN with the following exception:
Patients with known Gilbert disease: serum bilirubin level ≤ 3 ×ULN
Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula)
Serum albumin ≥ 2.5 g/dL
For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 ×ULN
within 14 days prior to initiation of study treatment
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• For men who are not surgically sterile: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures, and agreement to refrain
from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or
use a condom plus an additional contraceptive method that together result in a
failure rate of < 1% per year during the treatment period and for at least
3 months after the last dose of enzalutamide. Men must refrain from donating
sperm during this same period.
With pregnant female partners, men must remain abstinent or use a condom
during the treatment period and for 3 months after the last dose of
enzalutamide to avoid exposing the embryo.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical study and the preferred and usual lifestyle of the patient.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
Cancer-specific exclusions
• Treatment with any approved anti-cancer therapy, including chemotherapy,
immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of
abiraterone), within 4 weeks prior to initiation of study treatment
Palliative radiotherapy for bone metastases or soft tissue lesions should be
completed > 7 days prior to baseline imaging.
ADT with a gonadotropin-releasing hormone (GnRH) analog (GnRH agonist or
GnRH antagonist) is allowed.
• Treatment with abiraterone within 2 weeks prior to study treatment
• Use of herbal products that may have hormonal anti-prostate cancer activity and/or
are known to decrease PSA levels (e.g., saw palmetto) within 4 weeks of enrollment
• Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 4 weeks prior to initiation of study treatment
• Planned palliative procedures for alleviation of bone pain such as radiation therapy
(unless completed > 7 days prior to baseline imaging) and surgery.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone
metastases or metastases causing nerve impingement) should be treated prior
to initiation of study treatment.
• Structurally unstable bone lesions suggesting impending fracture
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled hypercalcemia defined as one or more of the following criteria:
Ionized calcium > 1.5 mmol/L
Serum calcium > 12 mg/dL
Corrected serum calcium greater than ULN (if serum albumin < 4.0 g/dL)
• Known or suspected brain metastasis or active leptomeningeal disease
Patients with treated epidural lesions and no other epidural progression are
allowed.
Asymptomatic metastatic lesions whose further growth would likely cause
functional deficits or intractable pain (e.g., epidural metastasis that is not
presently associated with spinal cord compression) should be considered for
loco-regional therapy if appropriate prior to initiation of study treatment.
General medical exclusions
• Malignancies other than mCRPC within 5 years prior to initiation of study treatment
Patients with malignancies of a negligible risk of metastasis or death (e.g., risk
of metastasis or death <5% at 5 years) are eligible provided they meet all of the
following criteria:
Malignancy treated with expected curative intent (e.g., adequately
treated basal or squamous cell skin cancer)
No evidence of recurrence or metastasis by follow-up imaging and any
disease-specific tumor markers
• Significant cardiovascular disease, such as New York Heart Association cardiac
disease (Class II or greater), myocardial infarction, or cerebrovascular accident
within 3 months prior to enrollment, unstable arrhythmia, or unstable angina
Patients with a known left ventricular ejection fraction (LVEF) < 40% will be
excluded.
Patients with known coronary artery disease, congestive heart failure not
meeting the above criteria, or LVEF 40%−50% must be on a stable medical
regimen that is optimized in the opinion of the treating physician, in consultation
with a cardiologist if appropriate. Patients with a history of clinically significant
cardiac disease (including anatomic abnormality, coronary artery disease,
congestive heart failure, abnormal LVEF, arrhythmia, or abnormal ECG) will be
required to undergo a screening echocardiogram.
History of clinically significant ventricular dysrhythmias (e.g., ventricular
tachycardia, ventricular fibrillation, torsades de pointes)
History of a Mobitz II second degree or third degree heart block without
permanent pacemaker in place
Hypotension (systolic blood pressure < 86 mmHg) or bradycardia with a heart
rate < 50 beats per minute at the screening visit
Uncontrolled hypertension as indicated by a resting systolic blood pressure
> 170 mm Hg or diastolic blood pressure > 105 mm Hg at the screening visit
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of
study treatment or anticipation of need for a major surgical procedure during the
course of the study
• Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may affect
the interpretation of the results, or may render the patient at high risk from treatment
complications
Patients who meet any of the following criteria will be excluded from study entry:
Cancer-specific exclusions
• Treatment with any approved anti-cancer therapy, including chemotherapy,
immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of
abiraterone), within 4 weeks prior to initiation of study treatment
Palliative radiotherapy for bone metastases or soft tissue lesions should be
completed > 7 days prior to baseline imaging.
ADT with a gonadotropin-releasing hormone (GnRH) analog (GnRH agonist or
GnRH antagonist) is allowed.
• Treatment with abiraterone within 2 weeks prior to study treatment
• Use of herbal products that may have hormonal anti-prostate cancer activity and/or
are known to decrease PSA levels (e.g., saw palmetto) within 4 weeks of enrollment
• Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 4 weeks prior to initiation of study treatment
• Planned palliative procedures for alleviation of bone pain such as radiation therapy
(unless completed > 7 days prior to baseline imaging) and surgery.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone
metastases or metastases causing nerve impingement) should be treated prior
to initiation of study treatment.
• Structurally unstable bone lesions suggesting impending fracture
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled hypercalcemia defined as one or more of the following criteria:
Ionized calcium > 1.5 mmol/L
Serum calcium > 12 mg/dL
Corrected serum calcium greater than ULN (if serum albumin < 4.0 g/dL)
• Known or suspected brain metastasis or active leptomeningeal disease
Patients with treated epidural lesions and no other epidural progression are
allowed.
Asymptomatic metastatic lesions whose further growth would likely cause
functional deficits or intractable pain (e.g., epidural metastasis that is not
presently associated with spinal cord compression) should be considered for
loco-regional therapy if appropriate prior to initiation of study treatment.
General medical exclusions
• Malignancies other than mCRPC within 5 years prior to initiation of study treatment
Patients with malignancies of a negligible risk of metastasis or death (e.g., risk
of metastasis or death <5% at 5 years) are eligible provided they meet all of the
following criteria:
Malignancy treated with expected curative intent (e.g., adequately
treated basal or squamous cell skin cancer)
No evidence of recurrence or metastasis by follow-up imaging and any
disease-specific tumor markers
• Significant cardiovascular disease, such as New York Heart Association cardiac
disease (Class II or greater), myocardial infarction, or cerebrovascular accident
within 3 months prior to enrollment, unstable arrhythmia, or unstable angina
Patients with a known left ventricular ejection fraction (LVEF) < 40% will be
excluded.
Patients with known coronary artery disease, congestive heart failure not
meeting the above criteria, or LVEF 40%−50% must be on a stable medical
regimen that is optimized in the opinion of the treating physician, in consultation
with a cardiologist if appropriate. Patients with a history of clinically significant
cardiac disease (including anatomic abnormality, coronary artery disease,
congestive heart failure, abnormal LVEF, arrhythmia, or abnormal ECG) will be
required to undergo a screening echocardiogram.
History of clinically significant ventricular dysrhythmias (e.g., ventricular
tachycardia, ventricular fibrillation, torsades de pointes)
History of a Mobitz II second degree or third degree heart block without
permanent pacemaker in place
Hypotension (systolic blood pressure < 86 mmHg) or bradycardia with a heart
rate < 50 beats per minute at the screening visit
Uncontrolled hypertension as indicated by a resting systolic blood pressure
> 170 mm Hg or diastolic blood pressure > 105 mm Hg at the screening visit
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of
study treatment or anticipation of need for a major surgical procedure during the
course of the study
• Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may affect
the interpretation of the results, or may render the patient at high risk from treatment
complications
The Estimated Number of Participants
-
Taiwan
29 participants
-
Global
730 participants
