Hormone therapy, or androgen deprivation therapy (ADT) is a standard way to treat prostate cancer. It works by reducing the amount of the main male sex hormone, testosterone in the body. Androgen receptor pathway inhibitors (ARPIs) are another type of hormone therapy. They either slow down how much testosterone is made or block testosterone from reaching the prostate cancer cells. Abiraterone acetate (AA) is an ARPI that is used to treat advanced prostate cancer. This type of treatment is usually given as a tablet with a steroid called prednisone/prednisolone to manage any medical problems from the hormone therapy. ASP5541 is a different form of AA. It is given as an injection into the muscle. In this study, ASP5541 will be given to men with advanced prostate cancer, both with and without prednisone/prednisolone. This study will check the safety of ASP5541 and compare how well ASP5541 works in men with advanced prostate cancer compared to AA. The main aims of the study are to check how well ASP5541 with prednisone/prednisolone works compared to AA with prednisone/prednisolone in men with advanced prostate cancer who haven't previously been treated with an ARPI, to check safety of ASP5541 given by itself in men with advanced prostate cancer that haven't previously been treated with an ARPI, to check how well ASP5541 given by itself works compared to AA with prednisone/prednisolone in men with advanced prostate cancer that haven't previously been treated with an ARPI, and to check safety of ASP5541 with prednisone/prednisolone in Japanese men with advanced prostate cancer. Adult men with a certain type of advanced prostate cancer can take part. Their cancer has spread to other parts of the body (metastatic). The different types are: Metastatic hormone-sensitive prostate cancer (mHSPC). Prostate cancer that needs testosterone to grow. Metastatic castration-resistant prostate cancer (mCRPC). Prostate cancer that continues to grow even when testosterone levels are low. In this study there will be 3 treatment groups. In Group 1 men with mCRPC who haven't previously been treated with an ARPI will either be given ASP5541 and prednisone/prednisolone or AA and prednisone/prednisolone. In Group 2 men with mHSPC who haven't previously been treated with an ARPI will either be given ASP5541 by itself or be given AA with prednisone/prednisolone. In Group 3 Japanese men with mCRPC or mHSPC who may or may not have previously been treated with an ARPI will be given ASP5541 with prednisone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
218
H. Lee Moffitt Cancer Center
Tampa, Florida, United States
RECRUITINGNew Mexico Oncology Hematology Consultants
Albuquerque, New Mexico, United States
RECRUITINGCarolina Urologic Research Center
Myrtle Beach, South Carolina, United States
RECRUITINGDE49004
Nürtingen, Baden-Wurttemberg, Germany
RECRUITINGNational Cancer Center Hospital East
Kashiwa, Chiba, Japan
RECRUITINGShizuoka Cancer Center
Sunto-gun, Shizuoka, Japan
RECRUITINGNippon Medical School Hospital
Bunkyo-ku, Tokyo, Japan
RECRUITINGThe Cancer Institute Hospital of JFCR
Koto-ku, Tokyo, Japan
RECRUITINGHarasanshin Hospital
Fukuoka, Japan
RECRUITINGOsaka International Cancer Institute
Osaka, Japan
RECRUITING...and 2 more locations
Proportion of androgen receptor pathway inhibitor (ARPI) -naïve metastatic castration-resistant prostate cancer (mCRPC) participants with Prostate Specific Antigen (PSA) decline ≥ 90% (Cohort 1)
PSA will be recorded from blood sample.
Time frame: Up to 37 months
Rate of no mineralocorticoid toxicity (Cohort 2 Group A, Safety run-in)
No mineralocorticoid toxicity is defined as experiencing neither Grade ≥ 1 hypokalemia nor Grade ≥ 2 hypertension.
Time frame: Up to 37 months
Proportion of metastatic hormone-sensitive prostate cancer (mHSPC) participants with prostate-specific antigen (PSA) ≤ 0.2 ng/mL (Cohort 2)
PSA will be recorded from blood sample.
Time frame: At 8 months
Dose-limiting toxicities (DLTs) (Cohort 3)
A DLT is defined as any event meeting the DLT criteria occurring during the first 28 days of treatment regardless of attribution to the study drug unless it is clearly related to disease progress or intercurrent illness.
Time frame: Up to Day 28
Number of participants with Adverse Events (AEs) (Cohort 3)
AEs will be coded using MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to 39 months
Number of Participants With Serious Adverse Events (SAEs) (Cohort 3)
An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is congenital anomaly/birth defect or other situations.
Time frame: Up to 39 months
Number of participants with laboratory value abnormalities and/or AEs (Cohort 3)
Number of participants with potentially clinically significant laboratory values.
Time frame: Up to 37 months
Number of participants with electrocardiogram (ECG) abnormalities and/or AEs (Cohort 3)
Number of participants with potentially clinically significant ECG values.
Time frame: Up to 36 months
Number of participants with vital sign abnormalities and/or AEs (Cohort 3)
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to 37 months
Number of participants with physical exam abnormalities and/or AEs (Cohort 3)
Number of participants with potentially clinically significant physical exam values.
Time frame: Up to 36 months
Eastern Cooperative Oncology Group (ECOG) Performance Status (Cohort 3)
The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Time frame: Up to 36 months
Radiographic progression-free survival (rPFS)
Radiographic progression-free survival (rPFS) is defined as the time from the date of randomization/first dose date until the date of radiological progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Prostate Cancer Working Group 3 (PCWG3) as determined by investigator or death from any cause.
Time frame: Up to 84 months
Prostate-specific antigen (PSA) decline ≥ 50% from baseline
Proportion of participants who had a PSA decline of ≥ 50% from baseline, confirmed by a second consecutive PSA assessment at least 3 weeks later.
Time frame: Up to 37 months
PSA decline ≥ 90% (Cohorts 2 & 3 only)
Proportion of participants who had a PSA decline of ≥ 90% from baseline, confirmed by a second consecutive PSA assessment at least 3 weeks later.
Time frame: Up to 37 months
PSA undetectable rate (≤ 0.2 ng/mL) (Cohorts 1 & 3)
Proportion of participants achieving a PSA level ≤ 0.2 ng/mL at any time post baseline.
Time frame: Up to 37 months
PSA undetectable rate (≤ 0.02 ng/mL)
Proportion of participants achieving a PSA level ≤ 0.02 ng/mL at any time post baseline.
Time frame: Up to 37 months
Time to PSA progression per PCWG3 criteria
Time from first dose date to the date of the first PSA value demonstrating a ≥ 25% increase and an absolute increase of ≤ 0.2 ng/mL above the nadir (i.e., the lowest PSA value observed post baseline or at baseline), which is confirmed by a second consecutive value at least 3 weeks later.
Time frame: Up to 37 months
Objective response rate (ORR)
Proportion of participants who achieved a confirmed Complete Response (CR) or Partial Response (PR) in their soft tissue disease using RECIST v1.1 criteria and PCWG3 for bone disease.
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Time frame: Up to 84 months
Duration of response (DOR)
Time from first date of confirmed CR or confirmed PR until the date of radiological PD per RECIST v1.1 and PCWG3 as determined by investigator or death from any cause.
Time frame: Up to 84 months
Best overall response (BOR)
The best response derived from all time points' overall responses (CR, PR, stable disease or non-CR/non-PD \[for participants with no measurable disease at baseline\], PD, not evaluable and not determined in order).
Time frame: Up to 84 months
Number of participants with Adverse Events (AEs) (Cohorts 1 & 2)
AEs will be coded using MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to 39 months
Number of Participants With Serious Adverse Events (SAEs) (Cohorts 1 & 2)
An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity is congenital anomaly/birth defect or other situations.
Time frame: Up to 39 months
Number of participants with laboratory value abnormalities and/or AEs (Cohorts 1 & 2)
Number of participants with potentially clinically significant laboratory values.
Time frame: Up to 37 months
Urine potassium (Cohort 2)
Potassium level will be recorded from urine sample.
Time frame: Up to 37 months
Urine creatinine (Cohort 2)
Creatinine level will be recorded from urine sample.
Time frame: Up to 37 months
Number of participants with electrocardiogram (ECG) abnormalities and/or AEs (Cohorts 1 & 2)
Number of participants with potentially clinically significant ECG values/cardiac monitoring.
Time frame: Up to 36 months
Number of participants with vital sign abnormalities and/or AEs (Cohorts 1 & 2)
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to 37 months
Number of participants with physical exam abnormalities and/or AEs (Cohorts 1 & 2)
Number of participants with potentially clinically significant physical exam values.
Time frame: Up to 36 months
ECOG Performance Status (Cohort 1 & 2 only)
The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Time frame: Up to 36 months
Number of participants with testosterone suppression to ≤ 1 ng/dL, or achieves a ≥ 90% reduction from baseline
Testosterone value will be recorded from blood sample.
Time frame: Up to 37 months
Mean testosterone value by timepoint
Testosterone value will be recorded from blood sample.
Time frame: Up to 37 months
Time to pain progression
Time to pain progression defined using pain scores from the Brief Pain Inventory - Short form (BPI-SF) and opiate analgesic use will be evaluated.
Time frame: Up to 36 months