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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: 225Ac-J591

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center Clinic
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

   1. PSA progression
   2. Objective radiographic progression in soft tissue
   3. New bone lesions
3. ECOG performance status of 0-2
4. 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.

5. Have previously been treated with at least one of the following:

   1. Androgen receptor signaling inhibitor (such as enzalutamide)
   2. CYP 17 inhibitor (such as abiraterone acetate)
6. Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
7. Age > 18 years

8. Patients must have normal organ and marrow function as defined below:

   1. Absolute neutrophil count >2,000 cells/mm3
   2. Hemoglobin ≥9 g/dL
   3. Platelet count >150,000 x 109/microliter
   4. Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
   5. Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal
   6. 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)
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 Cycle 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 known myelodysplastic syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Cancer Institute (NCI); United States Department of Defense; National Institutes of Health (NIH); Prostate Cancer Foundation
• Investigators: Principal Investigator: Scott Tagawa, MD, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2017
• Primary Completion (Actual): January 7, 2021
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: September 6, 2017
• First Posted (Actual): September 8, 2017

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Gallium 68 PSMA-11
• Other Study ID Numbers: 1706018281; 7R01CA207645-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No