The purpose of this study is to find out if re-treatment with 225Ac-J591 can be given without severe side effects.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
6
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.
Brooklyn Methodist Hospital - New York Presbyterian
Brooklyn, New York, United States
Weill Cornell Medicine
New York, New York, United States
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.
Time frame: Will be collected at the time of visit 1 through end of study or 100 months
Change in the number of subject with Prostate Specific Antigen (PSA) decline following 225Ac-J591 administration
PSA will be analyzed through blood specimen collection
Time frame: Will be collected at the time of visit 1 through end of study or 100 months
Change in adverse event rate response
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events
Time frame: 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)
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.
Time frame: Will be collected at the time of visit 1 through end of study or 100 months
Change in radiographic response rate
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
Time frame: Will be collected at the time of visit 1 through end of study or 100 months
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Change in circulating tumor cells (CTC) response
CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
Time frame: Will be collected at the time of visit 1 through end of study or 100 months
Change in progression-free survival following re-treatment doses of 225Ac-J591
Time frame: Will be collected at the time of visit 1 through end of study or 100 months
Change in Overall Survival Following re-Treatment Doses of 225Ac-J591
Overall survival will be captured through in-clinic or telephone contact with subjects
Time frame: Survival will be collected at the time of visit 1 through end of study or 100 months