Clinical Trials /

Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC

NCT04506567

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC
  • Official Title: Phase I/II Dose-escalation Study of Fractionated and Multiple Dose 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20-01021288
  • NCT ID: NCT04506567

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
225Ac−J591Dose- Fractionated Cohort

Purpose

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.

Detailed 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 and 8 weeks past last dose of
      225Ac-J591 for the multiple dose regimen (for subjects receiving 4 cycles, 26 weeks is
      expected). 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 PET 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. 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
    

Trial Arms

NameTypeDescriptionInterventions
Dose- Fractionated CohortExperimental
  • 225Ac−J591
Multiple Dose CohortExperimental
  • 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

               -  ECOG performance status of 0-2

          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. 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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

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.

Secondary Outcome Measures

Measure:Change in the number of subjects with radiographic response rate
Time Frame:Scans will be performed at screening, day 85 then again at end of study or 100 months
Safety Issue:
Description:Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications
Measure:Change in overall survival following fractionated dose and multiple doses of 225Ac-J591
Time Frame:Survival will be collected from Day 1 through study completion up to 100 months
Safety Issue:
Description:Overall survival will be captured through in-clinic or telephone contact with subjects
Measure:Change in disease assessment with 68Ga-PSMA-HBED-CC PET/CT prior to and following investigational treatment
Time Frame:Scans will be performed at screening, day 85 and day 168
Safety Issue:
Description:
Measure:Change in circulating tumor cells (CTC) response
Time Frame:Samples will be collected at screening, day 1, day 85 and at disease progression
Safety Issue:
Description:CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Weill Medical College of Cornell University

Last Updated

August 6, 2020