Re-treatment 225Ac-J591 for mCRPC

NCT04576871 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 20-01021286
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out if re-treatment with 225Ac-J591 can be given without severe side effects.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Change in the proportion of subjects in assessing safety of 225Ac-J591 in those previously treated with PSMA-TRT.

  Proportion of subjects with dose-limiting toxicity (DLT) from treatment cycle 1 to the end of the safety evaluation period at the end of the study. Acceptable safety is determined if no more than 2 (33%) of the subjects in a cohort experience DLT.

  Will be collected at the time of visit 1 through end of study or 100 months

Secondary Outcomes (7)

• Change in the number of subject with Prostate Specific Antigen (PSA) decline following 225Ac-J591 administration

  Will be collected at the time of visit 1 through end of study or 100 months

• Change in adverse event rate response

  Will be collected at the time of visit 1 through end of study or 100 months

• Change in the number of subjects with dose limiting toxicity (DLT)

  Will be collected at the time of visit 1 through end of study or 100 months

• Change in radiographic response rate

  Will be collected at the time of visit 1 through end of study or 100 months

• Change in circulating tumor cells (CTC) response

  Will be collected at the time of visit 1 through end of study or 100 months

Study Arms (2)

Heavily Exposed

EXPERIMENTAL

Drug: 225Ac-J591

Moderately Exposed

EXPERIMENTAL

Drug: 225Ac-J591

Interventions

225Ac-J591 DRUG

In this study, subject enrollment will be done in a re-treatment design. A single dose of 225Ac-J591 given at the specified dose per cohort. The initial planned dose level will be determined based upon prior radioactivity exposure level. Those with moderate exposure (up to 30 GBq of 177Lu) will start with 65 KBq/Kg and those with heavy prior exposure (more than 30 Gbq of 177Lu or any 225Ac) will start with 50 KBq/Kg.

Also known as: 68Ga-PSMA-HBED-CC injection for PET/CT Scan at screening, week 12 and week 24

Heavily Exposed; Moderately Exposed

Eligibility Criteria

• Age: 18 Years - 99 Years
• Gender Eligibility Details: Metastatic Castrate Resistant Prostate Cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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

You may not qualify if:

• 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 bone-seeking beta-emitting radioisotopes. Prior radium-223 is allowed provided last dose was at least 12 weeks prior to C1D1 on this protocol
• 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 ≤4 weeks of Day 1 Cycle 1
• 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 known myelodysplastic syndrome

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (2)

Brooklyn Methodist Hospital - New York Presbyterian

Brooklyn, New York, 11215, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Scott Tagawa, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: October 6, 2020
• Study Start: October 29, 2020
• Primary Completion: August 31, 2023
• Study Completion: May 31, 2024
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)