A Safety and Dose-finding Study of PRL-02 Depot in Men With Advanced Prostate Cancer

Recruiting now · Phase 1

Conditions studied: Prostate Cancer, Metastatic Castration Resistant Prostate Cancer, Metastatic Castration-sensitive Prostate Cancer

In brief

Medicines that reduce the amount of testosterone in the body are commonly used to treat prostate cancer. PRL-02 depot is a potential treatment for men with advanced prostate cancer. It is given by an injection into the muscle. Men with advanced prostate cancer can take part in this study. Their cancer has come back after previous cancer treatment, or the previous cancer treatment they had didn't work. The main aims of the study are: * to check the safety of PRL-02 depot given with and without another medicine called enzalutamide. * to check if the men can tolerate PRL-02 depot given with or without enzalutamide. * to find a suitable dose of PRL-02 depot. This study will be in 2 parts. In the first part, different small groups of men will receive lower to higher doses of PRL-02 depot together with other medicines. In the second part of the study, men who have previously taken a hormone therapy called abiraterone acetate or have previously taken 1 specific hormone therapy as part of their prostate cancer treatment can take part. Men in both parts of the study will receive injections of PRL-02 depot into a muscle once every 12 weeks. They will also take dexamethasone or prednisone, or enzalutamide once a day. The other medicines they take depend on which group and which part of the study they are in. During the study, the men will visit the clinic several times for health checks and scans. After the final visit, men whose cancer has not become worse will continue to have health checks and scans every few months.

Key facts

Study ID

NCT04729114

Run by

Astellas Pharma Global Development, Inc.

People needed

174

Starts

2021-06-14

Expected to finish

2029-05-31

Last updated by the study team

2026-02-04

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• Histological evidence of adenocarcinoma of the prostate
• Phase 1a Dose Escalation Groups A and B: participants must have one of the following documented conditions:
• mCSPC (must have documentation by positive bone scan [for bone disease] or metastatic lesions on computed tomography [CT] or magnetic resonance imaging [MRI] scan [for soft tissue])
• nmCSPC with biochemical relapse of prostate cancer
• mCSPC with oligometastatic prostate cancer (e.g., positron emission tomography positive)
• mCRPC (must have documentation by positive bone scan [for bone disease] or metastatic lesions on CT or MRI scan [for soft tissue])
• NOTE: For participants in the Dose Escalation Cohorts (including backfill) at each of the dose levels up to approximately 10 participants with ARPI-naïve mCRPC who have not received prior treatment with an ARPI (e.g., abiraterone acetate, enzalutamide, apalutamide, darolutamide) will be enrolled.
• Phase 1a Dose Escalation Groups A and B: participants with mCRPC must have evidence of disease progression defined as one or more of the following:
• Evidence of radiographic progression of disease following the most recent prostate cancer treatment, defined as progressive disease on CT/MRI per RECIST v1.1 or on a bone scan per PCWG3.
• PSA progression defined as the following:
• PSA nadir is defined as the lowest PSA during or after the most recent treatment. PSA progression is defined as an increased PSA of at least 25% and ≥1 ng/mL above the nadir confirmed by at least 2 measurements with a minimum of 1 week apart, and with at least 1 of the measurements within 90 days prior to screening.
• Participants with nmCSPC and biochemical recurrence, who had a radical prostatectomy (with or without radiotherapy) as the primary treatment for prostate cancer, must have a screening PSA ≥1 ng/mL. Participants with nmCSPC and biochemical recurrence who had radiotherapy only, as primary treatment for prostate cancer, must have a screening PSA ≥2 ng/mL above the nadir.
• Phase 1b Expansion Groups D and E: participants must have mCRPC Participants in Group D must have received prior treatment with abiraterone acetate, but must not have received treatment with other ARPIs (enzalutamide, apalutamide or darolutamide). Participants in Group E must have received prior treatment with only 1 of the following ARPIs: enzalutamide, apalutamide or darolutamide. Participants in both Groups D and E must have documented evidence of progression with one or more of the following:
• Evidence of radiographic progression of disease following the most recent prostate cancer treatment, defined as progressive disease on CT/MRI per RECIST v1.1 or on a bone scan per PCWG3. Disease spread that is limited to the regional pelvic lymph nodes does not qualify as radiographic progression.
• PSA progression defined as the following:
• PSA nadir is defined as the lowest PSA during or after the most recent treatment. PSA progression is defined as an increased PSA of at least 25% and ≥1 ng/mL above the nadir confirmed by at least 2 measurements with a minimum of 1 week apart, and with at least 1 of the measurements within 90 days prior to screening.
• Participants with mCRPC must have undergone bilateral orchiectomy or received concurrent GnRH agonist or antagonist therapy for at least 6 weeks prior to the first dose of study drug.
• Participants with mCSPC or nmCSPC with biochemical recurrence should have received <6 months of ADT with a GnRH agonist or antagonist or have a history of bilateral orchiectomy (i.e., surgical or medical castration) within 6 months prior to Day 1. Castration therapy (i.e., medical or surgical) must have been started at least 14 days prior to Cycle 1 Day 1 and participants should have no radiographic evidence of disease progression or rising PSA levels after starting ADT and prior to Cycle 1 Day 1.
• A serum testosterone level <50 ng/dL at screening (for mCRPC participants only)
• Adequate muscle mass for an i.m. injection
• An ECOG PS of 0 or 1
• Adequate bone marrow reserve defined as:
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelet count ≥100,000/µL
• Hemoglobin ≥9 gm/dL

You may not qualify if…

• Known active central nervous system (CNS) metastases. Note: Participants with CNS metastases that have been treated with surgery and/or radiation therapy, who are off pharmacologic doses of glucocorticoids, and who are neurologically stable are eligible.
• Impending bone fracture due to bone metastases
• Has a known additional malignancy beyond prostate cancer that required active treatment with the exception of any of the following:
• Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ carcinoma of any type
• Adequately treated Stage I cancer from which the participant is currently in remission and has been in remission for ≥2 years
• Any other cancer from which the participant has been disease-free for ≥5 years
• Clinically significant cardiac disease, defined as any of the following:
• Clinically significant cardiac arrhythmias including bradyarrhythmia which are poorly controlled.
• Congenital long QT syndrome
• QT interval corrected by Fridericia's formula (QTcF) ≥450 msec at screening (based on average of triplicate ECGs at baseline). If the QT interval corrected for heart rate intervals (QTc) is prolonged in a participant with a pacemaker or bundle branch block, the participant may be enrolled in the study if confirmed by the Medical Monitor.
• History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II or left ventricular ejection fraction measurement of <50% at baseline. Participants must not have unstable angina (symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months [NYHA Classification 2014].
• Uncontrolled hypertension, defined as systolic blood pressure (BP) >160 mmHg or diastolic BP >100 mmHg which has been confirmed by 2 successive measurements despite optimal medical management.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 3 months before start of study medication (except for adequately treated catheter-related venous thrombosis occurring >1 month before the start of study medication).
• Received an investigational drug within 4 weeks or 5 half-lives (whichever is shorter) of the first dose of study drug.
• Received chemotherapy within 2 weeks or 5 half-lives (whichever is shorter) of the first dose of study drug.
• Additional criteria: ARPI-naïve mCRPC participants enrolled in the Dose Escalation Cohorts (including backfill) must not have received prior chemotherapy in the mCRPC setting (prior receipt of chemotherapy in the mCSPC setting is allowed, if received at least 2 weeks or 5 half-lives prior to the first dose of study drug).
• Any unresolved NCI CTCAE criteria v5.0 Grade >2 toxicity from previous anticancer therapy at the Screening visit. Note: Participants receiving ongoing hormone replacement therapy for endocrine immune-related AEs without clinical symptoms will not be excluded.
• Has not recovered from recent major surgery or trauma
• Received a blood transfusion within 2 weeks of the first dose of study drug
• History of impaired pituitary or adrenal gland function (e.g., Addison's disease, Cushing's syndrome)
• Prior treatment with abiraterone acetate, orteronel. Exception: participants in Phase 1b Expansion Group D will have received prior abiraterone acetate, and participants in Group H may have received prior treatment with abiraterone acetate.
• Current treatment with systemic ketoconazole or any other CYP17 inhibitor. Participants who have received systemic ketoconazole or any other CYP17 inhibitor must have discontinued these agents ≥4 weeks prior to the first dose of study drug.
• Prior systemic treatment with an azole drug (e.g., fluconazole, itraconazole) within 4 weeks of first dose of study drug.
• Prior treatment with estrogens within 12 weeks of the first dose of study drug
• Need for systemic glucocorticoids greater than replacement doses; the use of topical, intraocular, inhalational, intranasal, or intra-articular glucocorticoids is permitted.

Where it is running

• Pan American Center for Oncology Trials, LLC — San Juan, Rio Piedras, Puerto Rico (enrolling)
• Los Angeles Cancer Network — Anaheim, California, United States (enrolling)
• Providence Medical Group Oncology Santa Rosa — Santa Rosa, California, United States (enrolling)
• Chesapeake Urology — Towson, Maryland, United States (enrolling)
• New Mexico Oncology Hematology Consultants Ltd — Albuquerque, New Mexico, United States (enrolling)
• Duke Cancer Center — Durham, North Carolina, United States (enrolling)
• MidLantic Urology — Bala-Cynwyd, Pennsylvania, United States (enrolling)
• Carolina Urologic Research Center — Myrtle Beach, South Carolina, United States (enrolling)
• Urology Associates PC — Nashville, Tennessee, United States (enrolling)
• Urology Clinics of North Texas — Dallas, Texas, United States (enrolling)
• Houston Metro Urology — Houston, Texas, United States (enrolling)
• University of Virginia Cancer Center — Charlottesville, Virginia, United States (enrolling)
• Northwest Medical Specialties — Tacoma, Washington, United States (enrolling)
• First Urology — Jeffersonville, Indiana, United States (enrolling)
• Wichita Urology Group — Wichita, Kansas, United States (enrolling)
• Florida Urology Partners — Tampa, Florida, United States
• Fort Wayne Medical Oncology and Hematology, Inc. — Fort Wayne, Indiana, United States
• Helios Clinical Research, LLC — Middleburg Heights, Ohio, United States
• Toledo Clinical Cancer Center — Toledo, Ohio, United States
• National Cancer Institute — Bethesda, Maryland, United States
• Urology San Antonio — San Antonio, Texas, United States
• XCancer Center Omaha/Urology Cancer Center — Omaha, Nebraska, United States
• Garden Sate Urology — Morristown, New Jersey, United States
• Arizona Urology Specialists — Tucson, Arizona, United States
• Oncology Consultants — Houston, Texas, United States

Full record on ClinicalTrials.gov

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