Clinical Trials /

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

NCT03276572

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 1706018281
  • NCT ID: NCT03276572

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
225Ac−J591All Subjects

Purpose

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. 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, and participants will also undergo a research PET/CT scan at screening and end of
      study. 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
All SubjectsExperimentalA single dose of 225Ac−J591 will be given to subjects with documented progressive metastatic CRPC.
  • 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:

             i. PSA progression ii. Objective radiographic progression in soft tissue iii. 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:

             i. Androgen receptor signaling inhibitor (such as enzalutamide) ii. 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:

             6.5.Absolute neutrophil count >2,000 cells/mm3 6.5.Hemoglobin ≥9 g/dL 6.5.Platelet
             count >150,000 x 109/uL 6.5.Serum creatinine <1.5 x upper limit of normal (ULN) or
             calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft−Gault 6.5.Serum total
             bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin
             must be normal 6.5. Serum AST and ALT <1.5 x ULN

          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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:The proportion of subjects with DLT from Visit 1 through End of Study Visit
Time Frame:up to 12 weeks
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

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

Last Updated