Re-treatment 225Ac-J591 for mCRPC

Early Phase 1

Recruiting

• Conditions: Prostate Cancer
• Interventions: Drug: 225Ac-J591

• Registration Number: NCT04576871
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

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

Detailed Description

This is an open-label, pilot study designed to determine the safety of PSMA-TRT re-treatment with 225Ac-J591, which will be given in a single dose on D1, in men with progressive mCRPC. If the patient responds and tolerates this dose, another may be given upon progression, provided at least 12 weeks after the initial dose.

This 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 and make men live longer. These treatments, however, are not curative so additional treatments are needed. Prostate-specific membrane antigen (PSMA) is a protein that is on the surface of most prostate cancer cells. It is absent from most other normal places in the body, but is present to some degree in the kidney, small intestine, salivary glands, and brain. J591 is a monoclonal antibody (an engineered protein) which recognizes PSMA. Actinium-225 (225Ac) is a small radioactive particle that emits alpha-particles (damaging/ionizing radiation). 225Ac-J591 is the combination compound that has the radioactive particle linked to J591. It is designed so that J591 will recognize PSMA and drags the radioactive particle 225Ac with it wherever it goes. This drug used currently is not FDA approved for any indication and is considered experimental.

In the first part of the study, a small group of subjects will receive a dose of 225Ac-J591 based upon a prior study. If that dose does not lead to severe side effects in many subjects, an additional small group will be treated. If the initial dose leads to too many severe side effects, another group will receive a lower dose. If it is determined by a physician that a subject's tumor has responded favorably to treatment, did not experience severe side effects and subject in agreement, then the subject will be allowed to receive one additional dose of the study drug 225Ac-J591, provided that at least 3 months have passed since the initial dose. For subjects receiving re-treatment, they will also participate in the same study procedures and followed for treatment including short-term and long-term follow up.

All treatment visits and all visits involving investigational PSMA PET imaging are required to be performed at the Weill Cornell Medicine - NewYork Presbyterian site located in the upper east side of Manhattan.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2020-09-24
• Study First Submitted QC: 2020-09-30
• Study First Posted: 2020-10-06
• Study Start: 2020-10-29
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-27
• Last Update Posted: 2023-10-31
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Heavily Exposed	225Ac-J591	-
Moderately Exposed	225Ac-J591	-

Primary Outcome Measures

Name	Time	Method
Change in the proportion of subjects in assessing safety of 225Ac-J591 in those previously treated with PSMA-TRT.	Will be collected at the time of visit 1 through end of study or 100 months	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.

Secondary Outcome Measures

Name	Time	Method
Change in Overall Survival Following re-Treatment Doses of 225Ac-J591	Survival will be collected at the time of visit 1 through end of study or 100 months	Overall survival will be captured through in-clinic or telephone contact with subjects
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	PSA will be analyzed through blood specimen collection
Change in adverse event rate response	Will be collected at the time of visit 1 through end of study or 100 months	National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events
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	DLTs will be measured by the recommended phase I fractionated dose and multiple dose regimens of 225Ac-J591 dose by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Change in radiographic response rate	Will be collected at the time of visit 1 through end of study or 100 months	Radiographic response rate will be captured through radiographic scans such as MRI, CT and bone scans. Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications
Change in circulating tumor cells (CTC) response	Will be collected at the time of visit 1 through end of study or 100 months	CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
Change in progression-free survival following re-treatment doses of 225Ac-J591	Will be collected at the time of visit 1 through end of study or 100 months

Trial Locations

Locations (2)

Brooklyn Methodist Hospital - New York Presbyterian; 🇺🇸 Brooklyn, New York, United States

Weill Cornell Medicine; 🇺🇸 New York, New York, United States