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Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC

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ClinicalTrials.gov Identifier: NCT04506567
Recruitment Status : Recruiting
First Posted : August 10, 2020
Last Update Posted : November 24, 2020
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Tracking Information
First Submitted Date  ICMJE August 6, 2020
First Posted Date  ICMJE August 10, 2020
Last Update Posted Date November 24, 2020
Actual Study Start Date  ICMJE August 18, 2020
Estimated Primary Completion Date June 30, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2020)
  • 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 ]
    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.
  • Cumulative maximum tolerated dose (MTD) [ Time Frame: Will be collected at the time of visit 1 through end of study or 100 months ]
    The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. Definition of the MTD usually relies on the sample, as MTD is defined as the dose level at which no more than two patients out of six experienced dose-limiting toxicity (DLT).
  • Assess the recommended phase II dose (RP2D) of 225Ac-J591 in fractionated dose and multiple dose regimens (phase I) [ Time Frame: Will be collected at the time of visit 1 through end of study or 100 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2020)
  • 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 ]
    Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications
  • 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 ]
    Overall survival will be captured through in-clinic or telephone contact with subjects
  • 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 ]
  • Change in circulating tumor cells (CTC) response [ Time Frame: Samples will be collected at screening, day 1, day 85 and at disease progression ]
    CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
  • Change in adverse event rate response [ Time Frame: Will be collected at the time of visit 1 through end of study or 100 months ]
    National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC
Official Title  ICMJE Phase I/II Dose-escalation Study of Fractionated and Multiple Dose 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer
Brief Summary 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

In schema 1 (dose-fractionated cohort), subject enrollment will be done in a fractionated dose-escalation study design at each dose level with treatment during one cycle to be administered on Day 1 and Day 15.

In schema 2 (multiple dose cohort), subject enrollment will be done in a dose-escalation single dose study design at each dose level with treatment administered as a single dose per cycle every 6 weeks up to 4 cycles.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: 225Ac-J591
    -Single cycle of fractionated dose of 225Ac-J591
  • Diagnostic Test: 68Ga-PSMA-HBED-CC injection
    68Ga-PSMA-HBED-CC before and after treatment
  • Drug: 225Ac-J591
    -Single dose of 225Ac-J591 every 6 weeks x 4
Study Arms  ICMJE
  • Experimental: Dose- Fractionated Cohort
    Interventions:
    • Drug: 225Ac-J591
    • Diagnostic Test: 68Ga-PSMA-HBED-CC injection
  • Experimental: Multiple Dose Cohort
    Interventions:
    • Diagnostic Test: 68Ga-PSMA-HBED-CC injection
    • Drug: 225Ac-J591
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 6, 2020)
105
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2027
Estimated Primary Completion Date June 30, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Adult male patients of >18 years age with documented progressive metastatic CRPC
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: GUONC Research Team 212-746-1480 guonc@med.cornell.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04506567
Other Study ID Numbers  ICMJE 20-01021288
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Weill Medical College of Cornell University
Study Sponsor  ICMJE Weill Medical College of Cornell University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Scott Tagawa, MD Weill Medical College of Cornell University
PRS Account Weill Medical College of Cornell University
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP