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

• ClinicalTrials.gov Identifier: NCT03276572
• Recruitment Status: Active, not recruiting
• First Posted: September 8, 2017
• Results First Posted: December 6, 2022
• Last Update Posted: December 6, 2022
• Sponsor: Weill Medical College of Cornell University
• Collaborators: Prostate Cancer Foundation; United States Department of Defense; National Institutes of Health (NIH); National Cancer Institute (NCI)
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Tracking Information

• First Submitted Date: August 3, 2017
• First Posted Date: September 8, 2017
• Results First Submitted Date: September 27, 2022
• Results First Posted Date: December 6, 2022
• Last Update Posted Date: December 6, 2022
• Actual Study Start Date: October 10, 2017
• Actual Primary Completion Date: January 7, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2022)

• Number of Subjects With Dose Limiting Toxicities (DLT) [ Time Frame: Assessed from start of treatment to up to 8 weeks after first study drug administration. ]
  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.
• Number of Subjects Who Reached Maximum Tolerated Dose (MTD) [ Time Frame: Assessed from start of treatment to up to 8 weeks after first study drug administration. ]
  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.

• Original Primary Outcome Measures (submitted: September 6, 2017): The proportion of subjects with DLT from Visit 1 through End of Study Visit [ Time Frame: up to 12 weeks ]

Current Secondary Outcome Measures (submitted: November 15, 2022)

• Number of Subjects With Prostate Specific Antigen (PSA) Response [ Time Frame: PSA was assessed at screening, and up to 6 months after first treatment with study drug. ]
  PSA will be analyzed through blood specimen collection
• Number of Subjects With Circulating Tumor Cells (CTC) Response [ Time Frame: CTC was assessed at screening and 12 weeks after starting study drug. ]
  CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
• Number of Subjects With Radiographic (Imaging) Response [ Time Frame: Response were assessed for patients throughout their duration on the study, up to 3 years. ]
  Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications
• Progression Free Survival (PFS) [ Time Frame: From the start of treatment to progression, up to 3 years ]
  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.

Original Secondary Outcome Measures (submitted: September 6, 2017)

• Rate of PSA decline following single dose of 225Ac-J591 measured by CTC response [ Time Frame: up to 12 weeks ]
• Radiographic response rate by RECIST criteria with PCWG3 modifications [ Time Frame: up to 12 weeks ]
• Biochemical and radiographic progression-free survival by RECIST criteria with PCWG3 modifications [ Time Frame: up to 12 weeks ]
• Overall survival following single dose of 225Ac-J591 [ Time Frame: up to 12 weeks ]
• Safety of single dose 225Ac-J591 as assessed by CTCAE 4 [ Time Frame: up to 12 weeks ]
• Changes in CTC count as measured by CellSearch [ Time Frame: up to 12 weeks ]
• Patient reported outcomes using FACT-P [ Time Frame: up to 12 weeks ]
• Patient reported outcomes using the Brief Pain Inventory short form [ Time Frame: up to 12 weeks ]
• Rate of favorable CTC count and LDH at 12 weeks following single dose 225Ac-J591 [ Time Frame: up to 12 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: September 6, 2017)

• Disease assessment with PSMA-ligand based imaging prior to and following investigational treatment [ Time Frame: up to 12 weeks ]
• Genomic DNA repair pathways in relationship to outcome following fractionated dose 225Ac-J591 [ Time Frame: up to 12 weeks ]

Descriptive Information

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

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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

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 Name: 68Ga-PSMA-HBED-CC injection for PET/CT Scan on day 1 and at end of study

Study Arms

Experimental: All Subjects

A single dose of 225Ac-J591 will be given to subjects with documented progressive metastatic CRPC.

Intervention: Drug: 225Ac-J591

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 15, 2022): 32
• Original Estimated Enrollment (submitted: September 6, 2017): 42
• Estimated Study Completion Date: July 2024
• Actual Primary Completion Date: January 7, 2021 (Final data collection date for primary outcome measure)

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:

   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

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Adult male patients of >18 years age with documented progressive metastatic CRPC

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03276572
• Other Study ID Numbers: 1706018281; 7R01CA207645-03 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Weill Medical College of Cornell University
• Original Responsible Party: Same as current
• Current Study Sponsor: Weill Medical College of Cornell University
• Original Study Sponsor: Same as current

Collaborators

• Prostate Cancer Foundation
• United States Department of Defense
• National Institutes of Health (NIH)
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Scott Tagawa, MD; Weill Medical College of Cornell University

• PRS Account: Weill Medical College of Cornell University
• Verification Date: November 2022