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

Clinical Trial Details

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. Following selection of the proper dose for each treatment regimen, the purpose of the phase II portion of the study is to test if the regimen of 225Ac-J591 leads to treatment response.
   
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 a lower 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 is used not FDA approved for any indication and is considered experimental.

Key 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. ECOG performance status of 0-2

  4. 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.

  5. 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)
  6. Have previously received taxane chemotherapy (in any disease state),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:
    • Absolute neutrophil count >2,000 cells/mm3
    • Hemoglobin ≥9 g/dL
    • Platelet count >150,000 x 109/L
    • 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)

  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 known myelodysplastic syndrome

Detailed eligibility will be reviewed when you contact the study team.

Study contact by location

Upper East Side - Manhattan

Contact(s)

June Greenberg, RN
(212) 746-2651
jdg2002@med.cornell.edu

Brooklyn

Primary Investigator(s)

Protocol ID(s)

Weill Cornell Medicine IRB #:

2001021288

ClinicalTrials.gov:

NCT04506567

Status

Open to Enrollment

Age Group

Adult

Sponsor

Disease