Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC

NCT ID: NCT04506567

Last Updated: 2025-06-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-18
• Study Completion Date: 2026-06-30

Brief 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. 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. The treatment phase is comprised of 8 weeks for the fractionated dose cohort (starting from cycle 1, day 1). For the multiple-dose cohort, the dose-limiting toxicity evaluation period is from date of first treatment through treatment on cycle 3, day 1. Following treatment, short-term follow up is planned until radiographic progression, expected to be 6 months.The study medication is called 225Ac-J591, and will be 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, subjects will undergo 68Ga-PSMA-HBED-CC injection and same day PET/CT at the end of study visit 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.

Key eligibility:

• Open to men age 18 and older.
• Diagnosis of progressive metastatic prostate cancer
• Have been previously treated for their disease with particular types of therapy

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose- Fractionated Cohort

Patients will receive a single cycle of 225Ac-J591, administered as a fractionated dose on days 1 and 15. This is a dose-escalation design, with up to 4 dosing cohorts.

Group Type: EXPERIMENTAL

225Ac-J591

Intervention Type: DRUG

Single cycle of fractionated dose of 225Ac-J591

68Ga-PSMA-HBED-CC injection

Intervention Type: DIAGNOSTIC_TEST

68Ga-PSMA-HBED-CC PET/CT before and after treatment

Multiple Dose Cohort

Patients will receive 225Ac-J591 every 6 weeks, with up to 4 doses. Some patients will be enrolled in a dose-escalation design, with up to 3 dosing cohorts. Additional patients will be enrolled at 2 lower dosing-cohorts.

Group Type: EXPERIMENTAL

68Ga-PSMA-HBED-CC injection

Intervention Type: DIAGNOSTIC_TEST

68Ga-PSMA-HBED-CC PET/CT before and after treatment

225Ac-J591

Intervention Type: DRUG

Single dose of 225Ac-J591 every 6 weeks x 4

Interventions

225Ac-J591

Single cycle of fractionated dose of 225Ac-J591

Intervention Type: DRUG

68Ga-PSMA-HBED-CC injection

68Ga-PSMA-HBED-CC PET/CT before and after treatment

Intervention Type: DIAGNOSTIC_TEST

225Ac-J591

Single dose of 225Ac-J591 every 6 weeks x 4

Intervention Type: DRUG

Other Intervention Names

68Ga-PSMA-11

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically confirmed adenocarcinoma of prostate

2. 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

3. 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

4. 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)

5. Have previously received taxane chemotherapy (in any disease state), been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.

6. Age > 18 years

7. 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)

8. ECOG performance status of 0-2

9. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

1. Implantation of investigational medical device ≤4 weeks of Treatment Visit 1 (Day 1) or current enrollment in oncologic investigational drug or device study

2. 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

3. Prior systemic beta-emitting bone-seeking radioisotopes

4. Known active brain metastases or leptomeningeal disease

5. History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1

6. 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

7. Radiation therapy for treatment of PC ≤4 weeks of Day 1 Cycle 1

8. 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

9. 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

10. 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

11. Known history of myelodysplastic syndrome

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph R Osborne, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Brooklyn Methodist Hospital - New York Presbyterian

Brooklyn, New York, United States

Weill Cornell Medicine

New York, New York, United States

Countries

United States

Other Identifiers

20-01021288

Identifier Type: -

Identifier Source: org_study_id