Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC

Prostate Cancer Clinical Trial

Official title:

Phase I/II Dose-escalation Study of Fractionated and Multiple Dose 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04506567
• Other study ID #: 20-01021288
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 18, 2020
• Est. completion date: June 30, 2027

Study information

• Verified date: August 2023
• Source: Weill Medical College of Cornell University
• Contact: GU Onc Research Team
• Phone: 212-746-1480
• Email: guonc[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the initial (phase I) portion of this study is to find a dose level and administration schedule of the study drug, 225Ac-J591, that can be given without severe side effects. The purpose of the second (phase II) portion of the study is to determine the proportion of those with PSMA-positive tumors with >50% PSA decline following 225Ac-J591 treatment in two regimens.

Description:

This clinical trial is for men with progressive metastatic castration resistant 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 weeks for the fractionated dose cohort (starting from cycle 1, day 1). For the multiple-dose cohort, the dose-limiting toxicity evaluation period is from date of first treatment through treatment on cycle 3, day 1. Following treatment, short-term follow up is planned until radiographic progression, expected to be 6 months.The study medication is called 225Ac-J591, and will be administered as a single fractionated cycle day 1 and day 15 in the fractionated dose regimen and as a single dose per cycle repeated every 6 weeks in the multiple dose regimen. Upon completion of investigational treatment with 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. 68Ga-PSMA-HBED-CC is comprised of gallium-68, which is a positron-emitting radionuclide linked to PSMA-HBED-CC (aka PSMA11), which is a small molecule targeting PSMA. 68Ga-PSMA-HBED-CC will be administered intravenously prior to PET/CT at screening and at follow up imaging x2. Subsequent 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 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 99 Years

Eligibility

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:

• PSA progression
• Objective radiographic progression in soft tissue
• New bone lesions

3. Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy

4. Have previously been treated with at least one of the following in any disease state:

• Androgen receptor signaling inhibitor (such as enzalutamide)
• CYP 17 inhibitor (such as abiraterone acetate)

5. Have previously received taxane chemotherapy (in any disease state), been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.

6. Age > 18 years

7. 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/uL
• 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)

8. ECOG performance status of 0-2

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 Treatment Visit 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 myelodysplastic syndrome

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• 225Ac-J591
Single cycle of fractionated dose of 225Ac-J591

Diagnostic Test:
• 68Ga-PSMA-HBED-CC injection
68Ga-PSMA-HBED-CC PET/CT before and after treatment

Drug:
• 225Ac-J591
Single dose of 225Ac-J591 every 6 weeks x 4

Locations

Country	Name	City	State
United States	Brooklyn Methodist Hospital - New York Presbyterian	Brooklyn	New York
United States	Weill Cornell Medicine	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with dose limiting toxicity (DLT)	DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Will be collected at the time of visit 1 through end of study or 100 months
Primary	Cumulative maximum tolerated dose (MTD)	The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. MTD is defined as the dose level at which no more than two patients out of six experienced dose-limiting toxicity (DLT).	Will be collected at the time of visit 1 through end of study or 100 months
Primary	Assess the recommended phase II dose (RP2D) of 225Ac-J591 in fractionated dose and multiple dose regimens (phase I)		Will be collected at the time of visit 1 through end of study or 100 months
Primary	Assess the proportion of those with PSMA+ tumors with >50% PSA decline following 225Ac-J591 in two regimens (phase II)	Proportion of patients achieving 50% or greater PSA decline (relative to baseline/pre-treatment PSA). Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy.	Will be collected at the time of visit 1 through end of study or 100 months
Secondary	Number of subjects with radiographic response	Response evaluation criteria in solid tumors RECIST (Version 1.1) criteria with prostate cancer working group 3 (PCWG3) modifications will be used	Scans will be performed at screening, day 85, then again at end of study or 100 months
Secondary	Overall survival following fractionated dose and multiple doses of 225Ac-J591	Overall survival will be captured through in-clinic or telephone contact with subjects	Survival will be collected from Day 1 through study completion up to 100 months
Secondary	Change in disease assessment with 68Ga-PSMA-11 PET/CT prior to and following investigational treatment	68Ga-PSMA-11 PET/CT will be utilized as part of the radiographic assessment.	Scans will be performed at screening, day 85 and day 168
Secondary	Change in circulating tumor cells (CTC) and the rate of favorable and undetectable CTC count at 12 weeks following 225Ac-J591	CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing	Samples will be collected at screening, day 1, day 85 and at disease progression
Secondary	Safety of treatment and adverse event rate	National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events	Will be collected at the time of visit 1 through end of study or 100 months
Secondary	Assess biochemical progression-free survival	PSA progression will be defined as a rise of > 25% above either the pretreatment level or the nadir PSA level (whichever is lowest). PSA must increase by > 2 ng/ml to be considered progression	Will be collected at the time of visit 1 through end of study or 100 months
Secondary	Assess the proportion with different levels of PSA decline following 225Ac-J591	PSA will be monitored through serial blood draws. Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy.	Will be collected at the time of visit 1 through end of study or 100 months