Phase I Trial of 225Ac-J591 in Patients With mCRPC

Study Overview
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Brief Summary
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This is an open-label, single-center Phase I dose escalation study designed to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of 225Ac-J591 in a single dose regimen.

Detailed Description
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This clinical trial is for men with advanced 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 visits over approximately 12 weeks. The study medication is called 225Ac-J591, and participants will receive an infusion of the study drug on the Treatment visit of the study. Upon completion of investigational treatment with single dose of 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. Subsequently 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 routine 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.

Official Title
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Phase I Dose-Escalation Trial of 225Ac-J591 in Patients With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: 225Ac-J591


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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. 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/microliter 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) Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Implantation of investigational medical device ≤4 weeks of Cycle 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 beta-emitting bone-seeking radioisotopes Known active brain metastases or leptomeningeal disease 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 for treatment of PC ≤4 weeks of Day 1 Cycle 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Subjects<br>A single dose of 225Ac-J591 will be given to subjects with documented progressive metastatic CRPC. | Drug: 225Ac-J591<br>* 225Ac-J591 (13.3 KBq/Kg - 93.3 KBq/Kg or 0.36 uCi/Kg - 2.52 uCi/Kg) on day 1<br>* Other names: 68Ga-PSMA-HBED-CC injection for PET/CT Scan on day 1 and at end of study;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Dose Limiting Toxicities (DLT) | Count of participants will be measured by the recommended phase II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for DLTs. | Assessed from start of treatment to up to 8 weeks after first study drug administration. | 
| Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | The MTD is the highest dose amongst the different dose-level cohorts in this study at which no more than 2 (33%) of the subjects in a cohort experience DLT. | Assessed from start of treatment to up to 8 weeks after first study drug administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Prostate Specific Antigen (PSA) Response | PSA will be analyzed through blood specimen collection | PSA was assessed at screening, and up to 6 months after first treatment with study drug. | 
| Number of Subjects With Circulating Tumor Cells (CTC) Response | CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing | CTC was assessed at screening and 12 weeks after starting study drug. | 
| Number of Subjects With Radiographic (Imaging) Response | Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications | Response were assessed for patients throughout their duration on the study, up to 3 years. | 
| Progression Free Survival (PFS) | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From the start of treatment to progression, up to 3 years |