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
  • SECONDARY ID: 7R01CA207645-03
  • NCT ID: NCT03276572

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
225Ac-J59168Ga-PSMA-HBED-CC injection for PET/CT Scan on day 1 and at end of studyAll 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. Upon completion of
      investigational treatment with single dose of 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. 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
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:

               1. PSA progression

               2. Objective radiographic progression in soft tissue

               3. 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:

               1. Androgen receptor signaling inhibitor (such as enzalutamide)

               2. 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:

               1. Absolute neutrophil count >2,000 cells/mm3

               2. Hemoglobin ≥9 g/dL

               3. Platelet count >150,000 x 109/microliter

               4. Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine
                  clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault

               5. Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case
                  direct bilirubin must be normal

               6. 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 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:Change in the number of subjects with dose limiting toxicities (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 II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Secondary Outcome Measures

Measure:Change in prostate specific antigen (PSA) response
Time Frame:Samples will be collected at Screening, Day 1, Day 8, Day 15, Day 29, Day 57, Day 85 then then every 4 weeks for 3 visits
Safety Issue:
Description:PSA will be analyzed through blood specimen collection
Measure:Change in circulating tumor cells (CTC) response
Time Frame:Samples will be collected at Screening, Day 1 and Day 85 visit then every 4 weeks for 3 visits
Safety Issue:
Description:CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
Measure:Change in the number of subjects with radiographic (imaging) response
Time Frame:Scans will be performed at Screening and Day 85
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 the number of subjects in patient reported outcomes (PRO) through Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire
Time Frame:Samples will be collected at Screening, Day 1, Day 8, Day 15, Day 29, Day 57, Day 85 then then every 4 weeks for 3 visits
Safety Issue:
Description:FACT-P questionnaire is a commonly used PRO assessing the health-related quality of life in men with prostate cancer. The FACT-p scale is measured from 0-4
Measure:Change in the number of subjects in patient reported outcomes(PRO) through Brief Pain Inventory (BPI) short form
Time Frame:Samples will be collected at Screening, Day 1, Day 8, Day 15, Day 29, Day 57, Day 85 then then every 4 weeks for 3 visits
Safety Issue:
Description:BPI is a questionnaire is utilized to assess the severity of pain and the impact it has on daily functioning. The scale is based on a rating of 0-10
Measure:Change in Biochemical and radiographic progression-free survival (PFS)
Time Frame:Scans will be captured at Screening and Day 85 then every 4 weeks for 3 visits then every 6 months for 3 years
Safety Issue:
Description:Radiographic evaluation will include bone scan, CT/MRI of abdomen/pelvis, and Chest x-ray (waived if CT/MRI includes chest). Prostate Cancer Working Group 3(PCWG3) modification will be utilized
Measure:Overall survival (OS) following single dose of 225Ac-J591
Time Frame:Survival will be collected from Day1 through study completion up to 100 months
Safety Issue:
Description:Overall survival will be captured through in-clinic or telephone contact with subjects

Details

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

Last Updated

February 28, 2020