Clinical Trials /

225Ac-J591 Plus 177Lu-PSMA-I&T for mCRPC

NCT04886986

Description:

This is a phase I/II dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA-I&T (also known as PNT2002). The two study drugs are 225Ac-J591 and 177Lu-PSMA-I&T. Both drugs are designed to deliver radiation to prostate cancer cells; they are known as radionuclide conjugates (radiation linked to antibodies/molecules that recognize prostate cancer cells). The first phase of the study (phase I) will determine the highest dose of the study drug that can be safely given. The second phase of the study (phase II) will determine the effectiveness of the drug combination in patients with prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 225Ac-J591 Plus 177Lu-PSMA-I&T for mCRPC
  • Official Title: Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20-08022486
  • NCT ID: NCT04886986

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
225Ac-J591All Subjects
177Lu-PSMA-I&T177Lu-PNT2002All Subjects
68Ga-PSMA-1168Ga-PSMA-HBED-CCAll Subjects

Purpose

This is a phase I/II dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA-I&T (also known as PNT2002). The two study drugs are 225Ac-J591 and 177Lu-PSMA-I&T. Both drugs are designed to deliver radiation to prostate cancer cells; they are known as radionuclide conjugates (radiation linked to antibodies/molecules that recognize prostate cancer cells). The first phase of the study (phase I) will determine the highest dose of the study drug that can be safely given. The second phase of the study (phase II) will determine the effectiveness of the drug combination in patients with prostate cancer.

Detailed Description

      This clinical trial is for men with progressive metastatic castration-resistant prostate
      cancer (mCRPC). The two primary objectives of this trial are to determine the highest dose of
      225Ac-J591 and 177Lu-PSMA-I&T that can be administered together (also known as maximum
      tolerated dose) and to determine the effectiveness of the drug combination. Patients who
      choose to participate in this study will have a screening visit to determine whether or not
      they are eligible for the study. The phase I component is a 3+3 dose-escalation design, with
      maximum two cohorts. 177Lu-PSMA-I&T will be given at a fixed dose of 6.8 GBq. 225Ac-J591 will
      be given starting at 30 KBq/kg, with a subsequent dose-escalation by an increment of 10
      KBq/kg to 40 KBq/kg. The two drugs will be co-administered every 8 weeks, for 2 cycles. Once
      the maximum tolerated dose has been established, the phase II component will enroll up to 24
      patients. The primary efficacy measure will be proportion of patients with PSA decline and
      proportion of patients with 50%+ PSA decline. Other objectives include to determine the
      radiographic response rate, biochemical progression-free survival, and overall survival.
      During the study, patients will be closely monitored for adverse events (side effects);
      weekly x4 weeks, then every 2 weeks until completion of therapy, then every 4 weeks until
      patients start another therapy. Long-term follow-up will be every 6 months, for 3 years.
      During the phase I component, the adverse event assessment phase will be a minimum of 8 weeks
      after the last dose of 225Ac-J591 and 177Lu-PSMA-I&T. At screening, week 12, and week 24,
      patients will undergo imaging. Imaging will include 68Ga-PSMA-11 PET/CT. 68Ga-PSMA-11 is
      comprised of gallium-68, a radiotracer, linked to PSMA-11, a molecule that binds to PSMA.
      Patients with PSMA-positive tumors are eligible for the study. Additional imaging includes
      SPECT imaging on day 8 of each cycle, to evaluate radiation uptake into the tumors.
    

Trial Arms

NameTypeDescriptionInterventions
All SubjectsExperimentalPatients enrolled in the study will receive the study drugs 225Ac-J591 and 177Lu-PSMA-I&T, along with 68Ga-PSMA-11.
  • 225Ac-J591
  • 177Lu-PSMA-I&T
  • 68Ga-PSMA-11

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of prostate

          -  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

          -  Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen
             deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone
             bilateral orchiectomy

          -  Have previously been treated with at least one of the following: Androgen receptor
             signaling inhibitor (such as enzalutamide), CYP 17 inhibitor (such as abiraterone
             acetate)

          -  Have previously received taxane chemotherapy, been determined to be ineligible for
             taxane chemotherapy by their physician or refused taxane chemotherapy

          -  Age > 18 years

          -  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: <1.5 x ULN in the absence of liver metastases; <3 x ULN if due to
             liver metastases (in both circumstances bilirubin must meet entry criteria)

          -  Ability to understand, and the willingness to sign, a written informed consent
             document

        Exclusion Criteria:

          -  Implantation of investigational medical device ≤4 weeks of Treatment visit #1 (Day 1)
             or current enrollment in oncologic investigational drug or device study

          -  Use of investigational drugs ≤4 weeks or <5 half-lives of Treatment visit # 1(Day 1)
             or current enrollment in investigational oncology drug or device study

          -  Prior systemic beta-emitting bone-seeking radioisotopes. Prior radium-223 is allowed
             provided at least 90 days have lapsed since last dose

          -  Prior PSMA-targeted radionuclide therapy (prior PSMA-targeted isotopes used for
             imaging/diagnostic purposes are allowed, as is prior PSMA-targeted therapy that does
             not involve therapeutic radionuclides)

          -  Known active brain or leptomeningeal metastases

          -  History of deep vein thrombosis and/or pulmonary embolus within 1 month of Treatment
             visit #1

          -  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

          -  Radiation therapy for treatment of PC ≤4 weeks of Treatment visit #1

          -  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

          -  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 at least 140 days after last study drug administration

          -  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

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

Primary Outcome Measures

Measure:Proportion of subjects with dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA-I&T during dose-escalation phase.
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 utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcome Measures

Measure:Change in biochemical progression-free survival
Time Frame:Will be collected at the time of visit 1 through end of study or 100 months
Safety Issue:
Description:PSA progression will be defined as a rise of > 25% above either the pretreatment level or the nadir PSA level (whichever is lowest). PSA must increase by > 2 ng/ml to be considered progression.
Measure:Change in circulating tumor cells (CTC) count
Time Frame:Samples will be collected at screening, week 12, week 24.
Safety Issue:
Description:CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
Measure:Number of subjects with radiographic response rate
Time Frame:Patients will undergo imaging at screening, week 12, and week 24.
Safety Issue:
Description:Response evaluation criteria in solid tumors RECIST (Version 1.1) criteria with prostate cancer working group 3 (PCWG3) modifications will be used.
Measure:Safety of treatment and adverse event rate
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:Overall survival following treatment with 225Ac-J591 and 177Lu-PSMA-I&T
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-11 PET/CT prior to and following investigational treatment
Time Frame:Patients will undergo imaging at screening, week 12, and week 24.
Safety Issue:
Description:68Ga-PSMA-11 PET/CT will be utilized as part of the radiographic assessment.

Details

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

Last Updated

May 14, 2021