Prostate CancerPhase 1NCT04506567
Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC
A Phase 1 study testing Multiple Dose of 225Ac-J591 at 45 KBq/kg, Multiple Dose of 225Ac-J591 at 55 KBq/kg and Multiple Dose of 225Ac-J591 at 65 KBq/kg in people with Prostate Cancer, run by Weill Medical College of Cornell University at 2 sites in United States.
Trial summary
The purpose of the initial (phase I) portion of this study is to find a dose level and administration schedule of the study drug, 225Ac-J591, that can be given without severe side effects. Read more about this study
- Who is it for?
- Ages 18 to 99 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Multiple Dose of 225Ac-J591 at 45 KBq/kg, Multiple Dose of 225Ac-J591 at 55 KBq/kg and Multiple Dose of 225Ac-J591 at 65 KBq/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Aug 2020to Dec 2026
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed adenocarcinoma of prostate
- Documented progressive metastatic CRPC based on Prostate Cancer Working
- Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
- PSA progression
- Objective radiographic progression in soft tissue
- New bone lesions
Show all 22Show fewer
- Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy
- Have previously been treated with at least one of the following in any disease state:
- Androgen receptor signaling inhibitor (such as enzalutamide)
- CYP 17 inhibitor (such as abiraterone acetate)
- Have previously received taxane chemotherapy (in any disease state), been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
- Age > 18 years
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count >2,000 cells/mm3
- Hemoglobin ≥9 g/dL
- Platelet count >150,000 x 109/uL
- Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
- Serum total bilirubin <1.5 x ULN (unless due to Gilbert's Syndrome in which case direct bilirubin must be normal)
- Serum AST and ALT <3 x ULN in absence of liver metastases; < 5x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)
- ECOG performance status of 0-2
- Ability to understand and the willingness to sign a written informed consent document
- For patients enrolled in the post-177Lu-PSMA-RL cohorts, must have previously received either 177Lu-PSMA-617 or 177Lu-PSMA-I\&T
Who cannot join
- Implantation of investigational medical device ≤4 weeks of Treatment Visit 1 (Day 1) or current enrollment in oncologic investigational drug or device study
- Use of investigational drugs ≤4 weeks or <5 half-lives of Cycle 1, Day 1 or current enrollment in investigational oncology drug or device study
- Prior systemic beta-emitting bone-seeking radioisotopes (e.g. samarium-153, strontium-89)
- For patients enrolled in the post-177Lu-PSMA-RL cohorts: prior radium-223
- Untreated hydronephrosis
- Known active brain metastases or leptomeningeal disease
Show all 15Show fewer
- History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1
- Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
- Radiation therapy for treatment of PC ≤4 weeks of Day 1 Cycle 1
- Chemotherapy for treatment of PC ≤4 weeks of Day 1 Cycle 1
- Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study
- Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration
- Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse
- Known history of myelodysplastic syndrome
- Bone scan with confluent lesions and lack of urinary tracer consistent with a "superscan" as determined by the investigator
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Brooklyn Methodist Hospital - New York Presbyterian
Brooklyn, New York, 11215
Weill Cornell Medicine
New York, New York, 10065
About this study
Official title: Phase I/II Dose-escalation Study of Fractionated and Multiple Dose 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer
The purpose of the initial (phase I) portion of this study is to find a dose level and administration schedule of the study drug, 225Ac-J591, that can be given without severe side effects. The purpose of the second (phase II) portion of the study is to determine the proportion of those with PSMA-positive tumors with >50% PSA decline following 225Ac-J591 treatment in two regimens.
Read the detailed description
This clinical trial is for men with progressive metastatic castration resistant prostate cancer. The purpose of this study is to find the highest dose level of the study drug, 225Ac-J591, that can be given without severe side effects. The research study is being done because the standard treatments for prostate cancer that has spread beyond the prostate gland are intended to minimize the adverse effects of the disease. These treatments, however, are not curative.
Patients who choose to participate in this study will have a screening visit to determine whether or not they are eligible to participate in the study. There are two different regimens for men with progressive mCRPC with and without prior 177Lu-PSMA-RL treatment.
The fractionated dose regimen is a single cycle of study drug administered on Day 1 and Day 15. The dose-limiting toxicity assessment period is 8 weeks for the fractionated dose regimen (starting from Cycle 1 Day 1).
The multiple dose regimen is a single dose of 225Ac-J591 per cycle, with each cycle administered every 6 weeks up to 4 cycles. The dose-limiting toxicity assessment period is up to 9 weeks past the 2nd dose of 225Ac-J591. Following treatment, short-term follow up is planned until radiographic progression, expected to be 6 months.
The study medication is called 225Ac-J591, and is administered as a single fractionated cycle day 1 and day 15 in the fractionated dose regimen and as a single dose per cycle repeated every 6 weeks in the multiple dose regimen. Upon completion of investigational treatment with 225Ac-J591, participants will undergo 68Ga-PSMA-HBED-CC injection and same day PET/CT to document treatment response. 68Ga-PSMA-HBED-CC is comprised of gallium-68, which is a positron-emitting radionuclide linked to PSMA-HBED-CC (aka PSMA11), which is a small molecule targeting PSMA. 68Ga-PSMA-HBED-CC will be administered intravenously prior to PET/CT at screening and at follow up imaging x2. Subsequent survival data and additional treatment(s) information will be captured from their routine standard of care (SOC) visits. During the other study visits, participants will undergo routine tests and procedures, such as physical examinations, and blood tests. Some blood tests will be done for research purposes only. After completion of therapy, participants may be contacted on a periodic basis to see how they are doing.
- Conditions
- Prostate Cancer
- Being tested
- Multiple Dose of 225Ac-J591 at 45 KBq/kg, Multiple Dose of 225Ac-J591 at 55 KBq/kg, Multiple Dose of 225Ac-J591 at 65 KBq/kg, Fractionated Dose of 225Ac-J591 at 45 KBq/kg, Fractionated Dose of 225Ac-J591 at 55 KBq/kg
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multiple Dose of 225Ac-J591 at 45 KBq/kgDrug
Multiple dose of 45 KBq/kg
Multiple Dose of 225Ac-J591 at 55 KBq/kgDrug
Multiple dose of 55 KBq/kg in dose-escalation regimen
Multiple Dose of 225Ac-J591 at 65 KBq/kgDrug
Multiple dose of 65 KBq/kg in dose-escalation regimen
Fractionated Dose of 225Ac-J591 at 45 KBq/kgDrug
Fractionated dose of 45 KBq/kg in dose-escalation regimen
Fractionated Dose of 225Ac-J591 at 55 KBq/kgDrug
Fractionated dose of 55 KBq/kg in dose-escalation regimen
Fractionated Dose of 225Ac-J591 at 60 KBq/kgDrug
Fractionated dose of 60 KBq/kg in dose-escalation and dose-expansion regimens
Fractionated Dose of 225Ac-J591 at 65 KBq/kgDrug
Fractionated dose of 65 KBq/kg in dose-escalation regimen
Fractionated Dose of 225Ac-J591 at 45 KBq/kg (Prior 177Lu-PSMA-RL)Drug
Fractionated dose of 45 KBq/kg for cohort of participants previously treated with 177Lu-PSMA-RL
Fractionated Dose of 225Ac-J591 at 50 KBq/kg (Prior 177Lu-PSMA-RL)Drug
Fractionated dose of 50 KBq/kg for cohort of participants previously treated with 177Lu-PSMA-RL
68Ga-PSMA-HBED-CC injectionDiagnostic test
68Ga-PSMA-HBED-CC PET/CT before and after treatment
| Study group | Role | What they receive |
|---|---|---|
| Multiple Dose 45 KBq/kg | Experimental | Participants in this multiple dose cohort received 45 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles. Receives: Drug: Multiple Dose of 225Ac-J591 at 45 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
| Multiple Dose 55 KBq/kg | Experimental | Participants in this multiple dose cohort received 55 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles. Receives: Drug: Multiple Dose of 225Ac-J591 at 55 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
| Multiple Dose 65 KBq/kg | Experimental | Participants in this multiple dose cohort received 65 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles. Receives: Drug: Multiple Dose of 225Ac-J591 at 65 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
| Fractionated Dose 45 KBq/kg | Experimental | Participants in this cohort received a single cycle of 45 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. Receives: Drug: Fractionated Dose of 225Ac-J591 at 45 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
| Fractionated Dose 55 KBq/kg | Experimental | Participants in this cohort received a single cycle of 55 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. Receives: Drug: Fractionated Dose of 225Ac-J591 at 55 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
| Fractionated Dose 60 KBq/kg | Experimental | Participants in this cohort receive a single cycle of 60 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15.
This was also the dose level for the expansion cohort of fractionated dose regimen. Receives: Drug: Fractionated Dose of 225Ac-J591 at 60 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
| Fractionated Dose 65 KBq/kg | Experimental | Participant in this cohort receive a single cycle of 65 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. Receives: Drug: Fractionated Dose of 225Ac-J591 at 65 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
| Fractionated Dose (prior 177Lu-PSMA-RL) 45 KBq/kg | Experimental | Participants in this cohort, who were previously treated with 177Lu-PSMA-RL, received a single cycle of 45 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. Receives: Drug: Fractionated Dose of 225Ac-J591 at 45 KBq/kg (Prior 177Lu-PSMA-RL); Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
| Fractionated Dose (prior 177Lu-PSMA-RL) 50 KBq/kg | Experimental | Participants in this cohort, who were previously treated with 177Lu-PSMA-RL, received a single cycle of 50 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. Receives: Drug: Fractionated Dose of 225Ac-J591 at 50 KBq/kg (Prior 177Lu-PSMA-RL); Diagnostic Test: 68Ga-PSMA-HBED-CC injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicity (DLT)
DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: Collected from Day 1 through 6 months
Maximum Tolerated Dose (MTD)
The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. MTD is defined as the dose level at which no more than two patients out of six experienced dose-limiting toxicity (DLT).
Measured: Collected from Day 1 through 6 months
Recommended Phase II Dose (RP2D) of 225Ac-J591 in Fractionated Dose and Multiple Dose Regimens Both Pre- and Post-treatment With 177Lu-PSMA-RL
Measured: Collected from Day 1 through 6 months
Number of Participants With PSMA-positive Tumors With >50% PSA Decline Following 225Ac-J591 in Each Cohort Regimen
Number of participants achieving greater than 50% PSA decline (relative to baseline/pre-treatment PSA). Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy
Measured: Collected from Day 1 through 6 months
Secondary outcomes (7)
Number of Participants With Radiographic Response
Response evaluation criteria in solid tumors RECIST (Version 1.1) criteria with prostate cancer working group 3 (PCWG3) modifications to be used.
Measured: Imaging performed at timepoints from Day 1 through study completion, approximately 3 years.
Overall Survival Following 225Ac-J591 Treatment
Overall survival will be captured through in-clinic or telephone contact with participants
Measured: Collected from Day 1 through study completion, approximately 3 years.
Change in Disease Assessment With 68Ga-PSMA-11 PET/CT Prior to and Following Investigational Treatment
Change in Maximum SUV (SUVmax) from Baseline 68Ga-PSMA-11 PET/CT to Post-therapy (Week 12) 68Ga-PSMA-11 PET/CT. 68Ga-PSMA-11 PET/CT was utilized as part of the radiographic assessment.
Measured: Scans performed during screening period (within 30 days of Cycle 1 Day 1) and at Day 85 from Cycle 1 Day 1.
Number of Participants With Change in Circulating Tumor Cells (CTC) Count at 12 Weeks Following 225Ac-J591
CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing. Number of participants with changes in CTC count.
Measured: Samples will be collected at Screening and Day 85
Number of Participants With Adverse Events
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events
Measured: Collected from Day 1 through study completion, approximately 3 years
Assess Biochemical Progression-free Survival
PSA progression will be defined as a rise of > 25% above either the pretreatment level or the nadir PSA level (whichever is lowest). PSA must increase by > 2 ng/ml to be considered progression
Measured: Collected from Day 1 through study completion, approximately 3 years
Assess the Proportion With Different Levels of PSA Decline Following 225Ac-J591
PSA will be monitored through serial blood draws. Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy.
Measured: Collected from Day 1 through study completion, approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2020
- Study start18 Aug 2020
- Primary completion1 Jun 2025
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants were enrolled to either the multiple dose cohort or the fractionated dose cohort in parallel, after which additional participants were enrolled in a prospective fractionated dose regimen (with prior 177Lu-PSMA-RL) and additional participants were enrolled in an expansion cohort of fractionated dose regimen at the R2PD of 60 KBq/kg. In a fractionated dose cohort, participants receive the dose level of treatment during one cycle to be administered on Day 1 and Day 15. In the multiple dose cohort, participants receive the dose level of treatment administered as a single dose per cycle every 6 weeks up to 4 cycles.
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph R Osborne, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04506567
- Sponsor's protocol ID
- 20-01021288
- Status last verified
- Aug 2026
- First submitted
- 6 Aug 2020
- Last updated
- 19 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stangl-Kremser J, Ricaurte-Fajardo A, Huicochea Castellanos S, Martinez-Fundichely A, Sun M, Osborne JR, Nauseef JT, Tagawa ST, Bander NH. Baseline Imaging Derived Factors of Response Following [225Ac]Ac-J591 Therapy in Metastatic Castration-Resistant Prostate Cancer: A Lesion Level Analysis. Prostate. 2025 Apr;85(5):502-509. doi: 10.1002/pros.24853. Epub 2025 Jan 23.
PubMed 39853781
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Dose-escalation Study of Fractionated and Multiple Dose 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT04506567
- Acronym / sponsor ID
- 20-01021288
- Conditions
- Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Study start
- 18 Aug 2020 (actual)
- Primary completion
- 1 Jun 2025 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 10 Aug 2020 (actual)
- Results
- Posted 19 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the initial (phase I) portion of this study is to find a dose level and administration schedule of the study drug, 225Ac-J591, that can be given without severe side effects. The purpose of the second (phase II) portion of the study is to determine the proportion of those with PSMA-positive tumors with >50% PSA decline following 225Ac-J591 treatment in two regimens.
Detailed description
This clinical trial is for men with progressive metastatic castration resistant prostate cancer. The purpose of this study is to find the highest dose level of the study drug, 225Ac-J591, that can be given without severe side effects. The research study is being done because the standard treatments for prostate cancer that has spread beyond the prostate gland are intended to minimize the adverse effects of the disease. These treatments, however, are not curative.
Patients who choose to participate in this study will have a screening visit to determine whether or not they are eligible to participate in the study. There are two different regimens for men with progressive mCRPC with and without prior 177Lu-PSMA-RL treatment.
The fractionated dose regimen is a single cycle of study drug administered on Day 1 and Day 15. The dose-limiting toxicity assessment period is 8 weeks for the fractionated dose regimen (starting from Cycle 1 Day 1).
The multiple dose regimen is a single dose of 225Ac-J591 per cycle, with each cycle administered every 6 weeks up to 4 cycles. The dose-limiting toxicity assessment period is up to 9 weeks past the 2nd dose of 225Ac-J591. Following treatment, short-term follow up is planned until radiographic progression, expected to be 6 months.
The study medication is called 225Ac-J591, and is administered as a single fractionated cycle day 1 and day 15 in the fractionated dose regimen and as a single dose per cycle repeated every 6 weeks in the multiple dose regimen. Upon completion of investigational treatment with 225Ac-J591, participants will undergo 68Ga-PSMA-HBED-CC injection and same day PET/CT to document treatment response. 68Ga-PSMA-HBED-CC is comprised of gallium-68, which is a positron-emitting radionuclide linked to PSMA-HBED-CC (aka PSMA11), which is a small molecule targeting PSMA. 68Ga-PSMA-HBED-CC will be administered intravenously prior to PET/CT at screening and at follow up imaging x2. Subsequent survival data and additional treatment(s) information will be captured from their routine standard of care (SOC) visits. During the other study visits, participants will undergo routine tests and procedures, such as physical examinations, and blood tests. Some blood tests will be done for research purposes only. After completion of therapy, participants may be contacted on a periodic basis to see how they are doing.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
- Model description
- Participants were enrolled to either the multiple dose cohort or the fractionated dose cohort in parallel, after which additional participants were enrolled in a prospective fractionated dose regimen (with prior 177Lu-PSMA-RL) and additional participants were enrolled in an expansion cohort of fractionated dose regimen at the R2PD of 60 KBq/kg. In a fractionated dose cohort, participants receive the dose level of treatment during one cycle to be administered on Day 1 and Day 15. In the multiple dose cohort, participants receive the dose level of treatment administered as a single dose per cycle every 6 weeks up to 4 cycles.
| Arm | Type | Receives |
|---|---|---|
| Multiple Dose 45 KBq/kg | Experimental | Drug: Multiple Dose of 225Ac-J591 at 45 KBq/kg, Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipants in this multiple dose cohort received 45 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles. |
| Multiple Dose 55 KBq/kg | Experimental | Drug: Multiple Dose of 225Ac-J591 at 55 KBq/kg, Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipants in this multiple dose cohort received 55 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles. |
| Multiple Dose 65 KBq/kg | Experimental | Drug: Multiple Dose of 225Ac-J591 at 65 KBq/kg, Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipants in this multiple dose cohort received 65 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles. |
| Fractionated Dose 45 KBq/kg | Experimental | Drug: Fractionated Dose of 225Ac-J591 at 45 KBq/kg, Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipants in this cohort received a single cycle of 45 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. |
| Fractionated Dose 55 KBq/kg | Experimental | Drug: Fractionated Dose of 225Ac-J591 at 55 KBq/kg, Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipants in this cohort received a single cycle of 55 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. |
| Fractionated Dose 60 KBq/kg | Experimental | Drug: Fractionated Dose of 225Ac-J591 at 60 KBq/kg, Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipants in this cohort receive a single cycle of 60 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. This was also the dose level for the expansion cohort of fractionated dose regimen. |
| Fractionated Dose 65 KBq/kg | Experimental | Drug: Fractionated Dose of 225Ac-J591 at 65 KBq/kg, Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipant in this cohort receive a single cycle of 65 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. |
| Fractionated Dose (prior 177Lu-PSMA-RL) 45 KBq/kg | Experimental | Drug: Fractionated Dose of 225Ac-J591 at 45 KBq/kg (Prior 177Lu-PSMA-RL), Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipants in this cohort, who were previously treated with 177Lu-PSMA-RL, received a single cycle of 45 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. |
| Fractionated Dose (prior 177Lu-PSMA-RL) 50 KBq/kg | Experimental | Drug: Fractionated Dose of 225Ac-J591 at 50 KBq/kg (Prior 177Lu-PSMA-RL), Diagnostic Test: 68Ga-PSMA-HBED-CC injectionParticipants in this cohort, who were previously treated with 177Lu-PSMA-RL, received a single cycle of 50 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histologically or cytologically confirmed adenocarcinoma of prostate
- Documented progressive metastatic CRPC based on Prostate Cancer Working
- Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy
- Have previously been treated with at least one of the following in any disease state:
- Have previously received taxane chemotherapy (in any disease state), been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
Key exclusion criteria (15 listed)
- Implantation of investigational medical device ≤4 weeks of Treatment Visit 1 (Day 1) or current enrollment in oncologic investigational drug or device study
- Use of investigational drugs ≤4 weeks or <5 half-lives of Cycle 1, Day 1 or current enrollment in investigational oncology drug or device study
- Prior systemic beta-emitting bone-seeking radioisotopes (e.g. samarium-153, strontium-89)
- For patients enrolled in the post-177Lu-PSMA-RL cohorts: prior radium-223
- Untreated hydronephrosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multiple Dose of 225Ac-J591 at 45 KBq/kgMultiple dose of 45 KBq/kg | Drug | Multiple Dose 45 KBq/kg |
| Multiple Dose of 225Ac-J591 at 55 KBq/kgMultiple dose of 55 KBq/kg in dose-escalation regimen | Drug | Multiple Dose 55 KBq/kg |
| Multiple Dose of 225Ac-J591 at 65 KBq/kgMultiple dose of 65 KBq/kg in dose-escalation regimen | Drug | Multiple Dose 65 KBq/kg |
| Fractionated Dose of 225Ac-J591 at 45 KBq/kgFractionated dose of 45 KBq/kg in dose-escalation regimen | Drug | Fractionated Dose 45 KBq/kg |
| Fractionated Dose of 225Ac-J591 at 55 KBq/kgFractionated dose of 55 KBq/kg in dose-escalation regimen | Drug | Fractionated Dose 55 KBq/kg |
| Fractionated Dose of 225Ac-J591 at 60 KBq/kgFractionated dose of 60 KBq/kg in dose-escalation and dose-expansion regimens | Drug | Fractionated Dose 60 KBq/kg |
| Fractionated Dose of 225Ac-J591 at 65 KBq/kgFractionated dose of 65 KBq/kg in dose-escalation regimen | Drug | Fractionated Dose 65 KBq/kg |
| Fractionated Dose of 225Ac-J591 at 45 KBq/kg (Prior 177Lu-PSMA-RL)Fractionated dose of 45 KBq/kg for cohort of participants previously treated with 177Lu-PSMA-RL | Drug | Fractionated Dose (prior 177Lu-PSMA-RL) 45 KBq/kg |
| Fractionated Dose of 225Ac-J591 at 50 KBq/kg (Prior 177Lu-PSMA-RL)Fractionated dose of 50 KBq/kg for cohort of participants previously treated with 177Lu-PSMA-RL | Drug | Fractionated Dose (prior 177Lu-PSMA-RL) 50 KBq/kg |
| 68Ga-PSMA-HBED-CC injection68Ga-PSMA-HBED-CC PET/CT before and after treatment | Diagnostic test | Fractionated Dose (prior 177Lu-PSMA-RL) 45 KBq/kg, Fractionated Dose (prior 177Lu-PSMA-RL) 50 KBq/kg, Fractionated Dose 45 KBq/kg, Fractionated Dose 55 KBq/kg, Fractionated Dose 60 KBq/kg, Fractionated Dose 65 KBq/kg, Multiple Dose 45 KBq/kg, Multiple Dose 55 KBq/kg, Multiple Dose 65 KBq/kg |
Primary outcome
Number of Participants With Dose Limiting Toxicity (DLT)
Time frame: Collected from Day 1 through 6 months
DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Maximum Tolerated Dose (MTD)
Time frame: Collected from Day 1 through 6 months
The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. MTD is defined as the dose level at which no more than two patients out of six experienced dose-limiting toxicity (DLT).
Recommended Phase II Dose (RP2D) of 225Ac-J591 in Fractionated Dose and Multiple Dose Regimens Both Pre- and Post-treatment With 177Lu-PSMA-RL
Time frame: Collected from Day 1 through 6 months
Number of Participants With PSMA-positive Tumors With >50% PSA Decline Following 225Ac-J591 in Each Cohort Regimen
Time frame: Collected from Day 1 through 6 months
Number of participants achieving greater than 50% PSA decline (relative to baseline/pre-treatment PSA). Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy
7 secondary outcomes
Number of Participants With Radiographic Response
Time frame: Imaging performed at timepoints from Day 1 through study completion, approximately 3 years.
Overall Survival Following 225Ac-J591 Treatment
Time frame: Collected from Day 1 through study completion, approximately 3 years.
Change in Disease Assessment With 68Ga-PSMA-11 PET/CT Prior to and Following Investigational Treatment
Time frame: Scans performed during screening period (within 30 days of Cycle 1 Day 1) and at Day 85 from Cycle 1 Day 1.
Number of Participants With Change in Circulating Tumor Cells (CTC) Count at 12 Weeks Following 225Ac-J591
Time frame: Samples will be collected at Screening and Day 85
Number of Participants With Adverse Events
Time frame: Collected from Day 1 through study completion, approximately 3 years
Assess Biochemical Progression-free Survival
Time frame: Collected from Day 1 through study completion, approximately 3 years
Assess the Proportion With Different Levels of PSA Decline Following 225Ac-J591
Time frame: Collected from Day 1 through study completion, approximately 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39853781Stangl-Kremser J, Ricaurte-Fajardo A, Huicochea Castellanos S, Martinez-Fundichely A, Sun M, Osborne JR, Nauseef JT, Tagawa ST, Bander NH. Baseline Imaging Derived Factors of Response Following [225Ac]Ac-J591 Therapy in Metastatic Castration-Resistant Prostate Cancer: A Lesion Level Analysis. Prostate. 2025 Apr;85(5):502-509. doi: 10.1002/pros.24853. Epub 2025 Jan 23.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph R Osborne, MD principal investigator
Weill Medical College of Cornell University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Multiple Dose of 225Ac-J591 at 45 KBq/kg, Multiple Dose of 225Ac-J591 at 55 KBq/kg and Multiple Dose of 225Ac-J591 at 65 KBq/kg in people with Prostate Cancer, run by Weill Medical College of Cornell University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicity (DLT) (time frame: Collected from Day 1 through 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04506567, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026; AzTrials last refreshed its copy on 1 Nov 2026.