NCT04886986
Phase I Study of 225Ac-J591 Plus 177Lu-PSMA Small Molecule for Progressive Metastatic Castration Resistant Prostate Cancer
Recruiting
PHASE1Ages 18–99InterventionalTreatmentWeill Medical College of Cornell UniversityInvestigator-initiated
~42 participants
Updated 2026-06-11 on ClinicalTrials.gov
What's tested:225Ac-J591177Lu-PSMA-61768Ga-PSMA-11177Lu-PSMA-I&T
At a glance
Recruiting sites
2 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA small molecule
Measured over From Cycle 1 Day 1 up to 12 weeks after Cycle 1 Day 1 (each cycle is 8 weeks).
+2 more outcomes measured
Conditions
Where it's being run
2 sites across 1 statesNew York2
Study leadership
- Joseph Osborne, MD · PRINCIPAL_INVESTIGATOR · Weill Medical College of Cornell University
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
ECOG performance status of 0-2
Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy
Have previously been treated with at least one of the following: Androgen receptor signaling inhibitor (such as enzalutamide), CYP 17 inhibitor (such as abiraterone acetate)
Have previously received taxane chemotherapy, 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: \<1.5 x ULN in the absence of liver metastases; \<3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)
Ability to understand, and the willingness to sign, a written informed consent document
Exclusion
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 Treatment visit # 1(Day 1) or current enrollment in investigational oncology drug or device study
Prior systemic beta-emitting bone-seeking radioisotopes. Prior radium-223 is allowed provided at least 90 days have lapsed since last dose
For the prior PSMA-TRT-naive cohort, prior PSMA-targeted radionuclide therapy is not allowed (prior PSMA-targeted isotopes used for imaging/diagnostic purposes are allowed, as is prior PSMA-targeted therapy that does not involve therapeutic radionuclides); For the 177Lu-PSMA small molecule exposed cohort, no dose limiting toxicity may have been observed during/after therapy with prior treatment and all other entry criteria must be met
Known active brain or leptomeningeal metastases
History of deep vein thrombosis and/or pulmonary embolus within 1 month of Treatment visit #1
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 Treatment visit #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 at least 140 days 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
Prior exposure to PARP inhibitor \> 2 weeks
What this trial measures
- Dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA small moleculeFrom Cycle 1 Day 1 up to 12 weeks after Cycle 1 Day 1 (each cycle is 8 weeks).
DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Cumulative maximum tolerated dose (MTD) or recommended phase II dose 225Ac-J591 and 177Lu-PSMA small moleculeFrom Cycle 1 Day 1 up to 12 weeks after Cycle 1 Day 1 (each cycle is 8 weeks).
The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. Definition of the MTD usually relies on the sample, as MTD is defined as the dose level at which no more than one patient out of six experienced dose-limiting toxicity (DLT).
- Proportion of PSMA+ subjects (by imaging criteria) with >50% PSA decline following treatment with the combination of 225Ac-J591 and 177Lu-PSMA small moleculeFrom Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).
Proportion of patients achieving 50% or greater 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.