Clinical Trials /

Re-treatment 225Ac-J591 for mCRPC

NCT04576871

Description:

The purpose of this study is to find out if re-treatment with 225Ac-J591 can be given without severe side effects.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Re-treatment 225Ac-J591 for mCRPC
  • Official Title: Pilot Study of PSMA-TRT Re-treatment Utilizing 225Ac-J591

Clinical Trial IDs

  • ORG STUDY ID: 20-01021286
  • NCT ID: NCT04576871

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
225Ac-J59168Ga-PSMA-HBED-CC injection for PET/CT Scan at screening, week 12 and week 24All Subjects

Purpose

The purpose of this study is to find out if re-treatment with 225Ac-J591 can be given without severe side effects.

Detailed Description

      This is a pilot study of single dose of 225Ac-J591 at 90 KBq/Kg in men with progressive
      mCRPC. If the patient responds and tolerates this dose, another may be given upon
      progression, provided at least 12 weeks after the initial dose.

      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 some 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 used currently is
      not FDA approved for any indication and is considered experimental.

      In the first part of the study, a small group of subjects will receive a dose of 225Ac-J591
      based upon a prior study. If that dose does not lead to severe side effects in many subjects,
      an additional small group will be treated. If the initial dose leads to too many severe side
      effects, another group will receive a lower dose. If it is determined by a physician that a
      subject's tumor has responded favorably to treatment, did not experience severe side effects
      and subject in agreement, then the subject will be allowed to receive one additional dose of
      the study drug 225Ac-J591, provided that at least 3 months have passed since the initial
      dose. For subjects receiving re-treatment, they will also participate in the same study
      procedures and followed for treatment including short-term and long-term follow up.

      All treatment visits and all visits involving investigational PSMA PET imaging are required
      to be performed at the Weill Cornell Medicine - NewYork Presbyterian site located in the
      upper east side of Manhattan.
    

Trial Arms

NameTypeDescriptionInterventions
All SubjectsExperimental
  • 225Ac-J591

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:

               -  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/ 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)

          9. Ability to understand and the willingness to sign a written informed consent document

         10. In the opinion of the investigator, history of clinical benefit with treatment using
             PSMA-TRT and no dose-limiting toxicity. Clinical benefit might be assessed by PSA
             changes, CTC changes, radiographic changes, and/or symptomatic improvement

        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 bone-seeking beta-emitting radioisotopes. Prior radium-223 is allowed
             provided last dose was at least 12 weeks prior to C1D1 on this protocol

          4. History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1

          5. 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

          6. Radiation therapy ≤4 weeks of Day 1 Cycle 1

          7. 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

          8. 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

          9. Known history of known myelodysplastic syndrome
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in the proportion of subjects in assessing safety of 225Ac-J591 in those previously treated with PSMA-TRT.
Time Frame:Will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:Proportion of subjects with dose-limiting toxcity (DLT) from treatment cycle 1 to the end of the safety evaluation period at the end of the study. Acceptable safety is determined if no more than 2 (33%) of the subjects in a cohort experience DLT.

Secondary Outcome Measures

Measure:Change in the number of subject with Prostate Specific Antigen (PSA) decline following 225Ac-J591 administration
Time Frame:Will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:PSA will be analyzed through blood specimen collection
Measure:Change in adverse event rate response
Time Frame:Will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events
Measure:Change in the number of subjects with dose limiting toxicity (DLT)
Time Frame:Will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:DLTs will be measured by the recommended phase I fractionated dose and multiple dose regimens of 225Ac-J591 dose by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure:Change in radiographic response rate
Time Frame:Will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:Radiographic response rate will be captured through radiographic scans such as MRI, CT and bone scans. Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications
Measure:Change in circulating tumor cells (CTC) response
Time Frame:Will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
Measure:Change in progression-free survival following re-treatment doses of 225Ac-J591
Time Frame:Will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:
Measure:Change in Overall Survival Following re-Treatment Doses of 225Ac-J591
Time Frame:Survival will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:Overall survival will be captured through in-clinic or telephone contact with subjects

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Weill Medical College of Cornell University

Last Updated

November 23, 2020