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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 abiraterone acetate. 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 abiraterone acetate.
The main aims of the study are:
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:
In this study there will be 3 treatment groups:
ASP5541 will be given as an injection into a muscle every 12 weeks. Men with mCRPC will take prednisone/prednisolone twice daily and men with mHSPC will take prednisone/prednisolone once daily. Abiraterone acetate will be given as tablets to be taken once daily. All groups will also receive the standard of care treatment, such as androgen deprivation therapy.
The men in the study will visit their clinic regularly during and after treatment for health checks, including checking for any medical problems. Some men (Group 2) will check their blood pressure weekly at home. On some visits they will also have scans to check for any changes in their cancer. The number of visits and type of safety checks done at each visit will depend on the health of each person and when they completed their treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (mCRPC) Group A | Experimental | Participants will receive ASP5541 every 12 weeks + prednisone/prednisolone twice daily |
|
| Cohort 1 (mCRPC) Group B | Active Comparator | Participants will receive abiraterone acetate once daily + prednisone/prednisolone twice daily |
|
| Cohort 2 (mHSPC) Group A (Safety Run In) | Experimental | Participants will receive ASP5541 every 12 weeks |
|
| Cohort 2 (mHSPC) Group B | Experimental | Participants will receive ASP5541 every 12 weeks |
|
| Cohort 2 (mHSPC) Group C | Active Comparator | Participants will receive abiraterone acetate once daily + prednisone/prednisolone once daily |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ASP5541 | Drug | Intramuscular Injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 84 months |
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Inclusion Criteria:
Note: Participant who has not had a bilateral orchiectomy must have a plan to maintain effective GnRH analogue therapy for the duration of the study.
If the participant has mCRPC, participant has evidence of disease progression defined as 1 or more of the following criteria at study entry:
If the participant has mCRPC, participant has a serum testosterone level < 1.73 nmol/L (< 50 ng/dL) at the Screening visit.
Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 7 months after final ASP5541 administration.
Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 7 months after final ASP5541 administration.
Male participant must not donate sperm during the treatment period and for 7 months after final ASP5541 administration.
Participant agrees not to participate in another interventional study while receiving ASP5541 in the present study.
Participant should have normal serum potassium (within the local laboratory normal range) at screening without supplementation.
Exclusion Criteria:
Participant has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.
Participant has known active central nervous system (CNS) metastases. Note: Participant with CNS metastases who has been treated with surgery and/or radiation therapy, who is off pharmacologic doses of glucocorticoids and who is neurologically stable is eligible.
Participant has a known additional malignancy beyond prostate cancer that requires active treatment with the exception of any of the following:
Participant has clinically significant cardiac disease, defined as any of the following:
Participant has any unresolved National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 5.0) Grade > 2 toxicity at the Screening visit. Note: Participant receiving ongoing hormone replacement therapy for endocrine immune-related AEs without clinical symptoms will not be excluded.
Participant has had major surgery (e.g., requiring general anesthesia) within 30 days before screening, or has not fully recovered from surgery, or has major surgery planned during the time the participant is expected to participate in the study.
Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 28 days prior to day 1.
Participant received a blood transfusion within 1 month of the first dose of study intervention.
Participant has a history of impaired pituitary or adrenal gland function (e.g., Addison's disease, Cushing's syndrome).
Participant has hemoglobin A1c (HbA1c) > 10% (if diabetes mellitus was previously diagnosed) or HbA1c > 8% (if diabetes mellitus was previously undiagnosed). (Excluded participant may be rescreened after referral and evidence of improved control of their condition.)
Participant has jaundice or known current active liver disease from any cause, including hepatitis A (hepatitis A virus IgM positive, but testing for hepatitis A in screening is not required), hepatitis B (hepatitis B virus surface antigen positive, confirmed by hepatitis B virus DNA), or hepatitis C (hepatitis C virus antibody positive, confirmed by hepatitis C virus RNA).
Participant has moderate or severe hepatic impairment (Child-Pugh Class B or C).
Participant has a known history of human immunodeficiency virus (HIV) infection (HIV antibody positive).
Participant has a body mass index > 40 kg/m2.
Participant has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria within 2 years before screening.
Participant received treatment with glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to C1D1. The use of topical, intraocular, inhalational, intranasal or intra-articular glucocorticoids is permitted.
Participant received treatment with herbal medications with known anti-cancer properties or known effects on prostate physiology within 4 weeks prior to Cycle 1 Day 1 (e.g., saw palmetto, St. John's wort, turmeric/curcumin). Participants must agree not to use herbal products during study participation.
Participant is receiving current treatment with systemic ketoconazole, abiraterone acetate (AA) or any other cytochrome P450 17A1 (CYP17) inhibitor. Participant who has received systemic ketoconazole, AA or any other CYP17 inhibitor must have discontinued these agents ≥ 4 weeks prior to the first dose of study intervention.
Participant received prior systemic treatment with a strong inducer or inhibitor of cytochrome p450 3A4 (CYP3A4) within 4 weeks of first dose of study intervention. Concomitant use of strong inducers or inhibitors of CYP3A4 are not permitted on study.
Participant requires use of biotin (i.e., vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 μg. Note: Participant who switches from a high dose to a dose of 30 μg/day or less prior to first dose of study drug is eligible for study entry.
Participant is required to use any prohibited medication on the List of Excluded Concomitant Medications.
For mCRPC participants only: Participant has been treated with any of the following for prostate cancer, during the indicated time frame prior to enrollment:
For mHSPC participants only: Participant has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer (the following exceptions are permitted):
Participant has received any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to C1D1.
Participant has received ASP5541 previously.
Participant has absolute neutrophil count < 1500/μL, platelet count < 100000/μL or hemoglobin < 9 g/dL (6.2 mmol/L) or international normalized ratio (INR) ≥ 1.5 (unless participant is taking oral anticoagulants in which case INR ≤ 2.0 is permitted) at Screening. Note: Participant may not have received any growth factors within 7 days or blood transfusions within 28 days prior to the hematology values obtained at Screening.
Participant has serum total bilirubin > 1.5 x upper limit of normal (ULN) (or > 3 x ULN for participants with documented Gilbert's disease), or serum alanine aminotransferase or aspartate aminotransferase > 2.5 x ULN at Screening.
Participant does not have adequate renal function defined as a calculated creatinine clearance < 30 mL/min as determined by a validated algorithm for calculating creatinine clearance.
Participant has serum albumin < 3.0 g/dL (30 g/L) at Screening.
Participant has a known or suspected hypersensitivity to ASP5541, prednisone, or any components of the formulations used.
Participant has a gastrointestinal disorder affecting absorption.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Astellas Pharma Global Development, Inc. | Contact | 800-888-7704 | Astellas.registration@astellas.com |
| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Astellas Pharma Global Development, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clearview Cancer Institute | Recruiting | Huntsville | Alabama | 35805 | United States | |
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
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| Cohort 3 (mCRPC or mHSPC) Japanese Participants Only | Experimental | Participants will receive ASP5541 every 12 weeks + prednisone/prednisolone twice daily (for mCRPC) or prednisone/prednisolone once daily (for mHSPC) |
|
|
| Prednisone | Drug | Oral |
|
| Prednisolone | Drug | Oral |
|
| abiraterone acetate | Drug | Oral |
|
| Adrenocorticotropic hormone | Drug | Intramuscular or intravenous injection |
|
| 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. | 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. | 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. | 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. | 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. | Up to 36 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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. | 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. | 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. | Up to 37 months |
| Urine potassium (Cohort 2) | Potassium level will be recorded from urine sample. | Up to 37 months |
| Urine creatinine (Cohort 2) | Creatinine level will be recorded from urine sample. | 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. | 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. | 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. | 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. | 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. | Up to 37 months |
| Mean testosterone value by timepoint | Testosterone value will be recorded from blood sample. | Up to 37 months |
| Median time to testosterone suppression of levels ≤ 1 ng/dL | Time to testosterone suppression is defined as time from date of randomization/first dose date until testosterone suppression to ≤ 1 ng/mL. | 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. | Up to 36 months |
| Sharp HealthCare - Sharp Memorial Hospital |
| Recruiting |
| San Diego |
| California |
| 92123 |
| United States |
| H. Lee Moffitt Cancer Center | Recruiting | Tampa | Florida | 33612 | United States |
| Associated Urological Specialists | Recruiting | Chicago Ridge | Illinois | 60415 | United States |
| NorthShore University HealthSystem | Recruiting | Evanston | Illinois | 60201 | United States |
| Ochsner Health - Ochsner Medical Center - New Orleans | Recruiting | New Orleans | Louisiana | 70121 | United States |
| New Mexico Oncology Hematology Consultants | Recruiting | Albuquerque | New Mexico | 87109 | United States |
| Solaris Health - The Urology Group | Recruiting | Cincinnati | Ohio | 45212 | United States |
| Carolina Urologic Research Center | Recruiting | Myrtle Beach | South Carolina | 29572 | United States |
| Tennessee Oncology Nashville | Recruiting | Nashville | Tennessee | 37203 | United States |
| University of Virginia Cancer Center | Recruiting | Charlottesville | Virginia | 22908-07 | United States |
| UW Health Carbone Cancer Center | Recruiting | Madison | Wisconsin | 53792 | United States |
| Subei People's Hospital | Recruiting | Yangzhou | Jiangsu | 225001 | China |
| The Second Hospital of Tianjin Medical University | Recruiting | Tianjin | Tianjin Municipality | 300211 | China |
| The First Affiliated Hospital, Zhejiang University School of Medicine | Recruiting | Hangzhou | Zhejiang | China |
| Huai'an First People's Hospital | Recruiting | Huaian | 211731 | China |
| Renji Hospital Shanghai Jiaotong Univ School of Medicine | Recruiting | Shanghai | 200127 | China |
| Site FR33008 | Recruiting | Lille | France |
| Site FR33004 | Recruiting | Strasbourg | France |
| Site DE49004 | Recruiting | Nürtingen | Baden-Wurttemberg | Germany |
| Site DE49001 | Recruiting | Heinsberg | Germany |
| Site IT39004 | Recruiting | Milan | Italy |
| Site IT39006 | Recruiting | Milan | Italy |
| Site IT39005 | Recruiting | Roma | Italy |
| Site IT39003 | Recruiting | Trento | Italy |
| National Cancer Center Hospital East | Recruiting | Kashiwa | Chiba | Japan |
| Shizuoka Cancer Center | Recruiting | Sunto-gun | Shizuoka | Japan |
| Nippon Medical School Hospital | Recruiting | Bunkyo-ku | Tokyo | Japan |
| The Cancer Institute Hospital of JFCR | Recruiting | Koto | Tokyo | Japan |
| Harasanshin Hospital | Recruiting | Fukuoka | Japan |
| Osaka International Cancer Institute | Recruiting | Osaka | Japan |
| Site PL48005 | Recruiting | Mysłowice | Poland |
| Site PL48008 | Recruiting | Otwock | Poland |
| PanOncology Trials | Recruiting | San Juan | Puerto Rico |
| Site KR82008 | Recruiting | Gwangju | South Korea |
| Site KR82002 | Recruiting | Seoul | South Korea |
| Site KR82003 | Recruiting | Seoul | South Korea |
| Site KR82004 | Recruiting | Seoul | South Korea |
| Site KR82007 | Recruiting | Seoul | South Korea |
| Site ES34006 | Recruiting | Barcelona | Catalonia | Spain |
| Site ES34008 | Recruiting | Barcelona | Spain |
| Site ES34001 | Recruiting | Madrid | Spain |
| Site ES34003 | Recruiting | Santiago de Compostela | Spain |
| Site TW88603 | Recruiting | Kaohsiung City | Taiwan |
| Site TW88602 | Recruiting | Taipei | Taiwan |
| Site GB44003 | Recruiting | London | United Kingdom |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D011241 | Prednisone |
| D011239 | Prednisolone |
| D000069501 | Abiraterone Acetate |
| D000324 | Adrenocorticotropic Hormone |
| ID | Term |
|---|---|
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D011246 | Pregnadienetriols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D053486 | Melanocortins |
| D011333 | Pro-Opiomelanocortin |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
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