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Prostate CancerPhase 1NCT04886986

Phase I Study of 225Ac-J591 Plus 177Lu-PSMA Small Molecule for Progressive Metastatic Castration Resistant Prostate Cancer

A Phase 1 study testing 225Ac-J591, 177Lu-PSMA-617 and 68Ga-PSMA-11 in people with Prostate Cancer, run by Weill Medical College of Cornell University at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a phase I dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA small molecule. Both drugs are designed to deliver radiation to prostate cancer cells; they are known as radionuclide conjugates (radiation linked to antibodies/molecules that recognize prostate cancer cells). 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?
225Ac-J591, 177Lu-PSMA-617 and 68Ga-PSMA-11
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
2 sitesUnited States
Study dates
30 Jun 2021to Dec 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

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
  • 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
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  • 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

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 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
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  • 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

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

GUONC Research Team contact

212-746-1480

guonc@med.cornell.edu

United States2 sites, 2 recruiting

  • Brooklyn Methodist Hospital - New York Presbyterian

    Brooklyn, New York, 11215

    Lina Flores, RN, 646-923-5883, lif9061@nyp.org

    David Nanus, MD

    Recruiting

  • Weill Cornell Medicine New York Presbyterian

    New York, New York, 10065

    GUONC Research Team, guonc@med.cornell.edu

    Joseph Osborne, MD

    Recruiting

Other trials in United States

About this study

This is a phase I dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA small molecule. Both drugs are designed to deliver radiation to prostate cancer cells; they are known as radionuclide conjugates (radiation linked to antibodies/molecules that recognize prostate cancer cells). This phase of the study (phase I) will determine the highest dose of the study intervention that can be safely given.

Read the detailed description

This clinical trial is for men with progressive metastatic castration-resistant prostate cancer (mCRPC). The two primary objectives of this trial are to determine the highest dose of 225Ac-J591 and 177Lu-PSMA-small molecule that can be administered together (also known as maximum tolerated dose) with the recommended phase II dose and to determine the effectiveness of the drug combination. The two drugs will be co-administered every 8 weeks, for 2 cycles.

Conditions
Prostate Cancer
Being tested
225Ac-J591, 177Lu-PSMA-617, 68Ga-PSMA-11, 177Lu-PSMA-I&T
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 225Ac-J591Drug

    30 - 40 KBq/kg (dose-escalation) every 8 weeks, for up to 2 cycles. Administered together with 177Lu-PSMA-617. Intravenous administration.

  • 177Lu-PSMA-617Drug

    6.8 - 7.4 GBq received every 8 weeks, for up to 2 cycles. Administered together with 225Ac-J591. Intravenous administration.

  • 68Ga-PSMA-11Drug

    Also called 68Ga-PSMA-HBED-CC

    [185 ±74 MBq or 5 ±2 mCi] intravenous during screening, 12 weeks, 24 weeks. Imaging agent for PSMA PET/CT.

  • 177Lu-PSMA-I&TDrug

    6.8 GBq received every 8 weeks, up to 2 cycles. Administered together with 225Ac-J591. Intravenous administration.

Study groups in NCT04886986
Study groupRoleWhat they receive
Combination of 225Ac-J591 and 177Lu-PSMA-I&TExperimentalParticipants who received the combination of 225Ac-J591 and 177Lu-PSMA-I\&T, along with 68Ga-PSMA-11.
Receives: Drug: 225Ac-J591; Drug: 68Ga-PSMA-11; Drug: 177Lu-PSMA-I&T
Combination of 225Ac-J591 and 177Lu-PSMA-617ExperimentalParticipants will receive the study drugs 225Ac-J591 and 177Lu-PSMA-617, along with 68Ga-PSMA-11.
Receives: Drug: 225Ac-J591; Drug: 177Lu-PSMA-617; Drug: 68Ga-PSMA-11

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA small molecule

    DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: From Cycle 1 Day 1 up to 12 weeks after Cycle 1 Day 1 (each cycle is 8 weeks).

  2. Cumulative maximum tolerated dose (MTD) or recommended phase II dose 225Ac-J591 and 177Lu-PSMA small molecule

    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).

    Measured: From Cycle 1 Day 1 up to 12 weeks after Cycle 1 Day 1 (each cycle is 8 weeks).

  3. Proportion of PSMA+ subjects (by imaging criteria) with >50% PSA decline following treatment with the combination of 225Ac-J591 and 177Lu-PSMA small molecule

    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.

    Measured: From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).

Secondary outcomes (6)

  1. Change in 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: From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).

  2. Change in circulating tumor cells (CTC) count

    CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing

    Measured: Samples will be collected at screening, week 12, week 24.

  3. 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 will be used.

    Measured: Patients will undergo imaging at screening, week 12, and week 24.

  4. 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: From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).

  5. Overall survival following treatment with 225Ac-J591 and 177Lu-PSMA small molecule

    Overall survival will be captured through in-clinic or telephone contact with subjects

    Measured: From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).

  6. Change in disease assessment with 68Ga-PSMA-11 PET/CT prior to and following investigational treatment

    68Ga-PSMA-11 PET/CT will be utilized as part of the radiographic assessment.

    Measured: Patients will undergo imaging at screening, week 12, and week 24.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 May 2021
  2. Study start30 Jun 2021
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

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
Single group
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04886986
Sponsor's protocol ID
20-08022486
Status last verified
Jun 2026
First submitted
11 May 2021
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 225Ac-J591, 177Lu-PSMA-617 and 68Ga-PSMA-11 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 9 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 11 Jun 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact GUONC Research Team (212-746-1480, guonc@med.cornell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA small molecule (time frame: From Cycle 1 Day 1 up to 12 weeks after Cycle 1 Day 1 (each cycle is 8 weeks).). The study lists 3 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 NCT04886986.

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 11 Jun 2026.

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