Clinical Trials /

Phase I Dose-escalation Study of Fractionated 177Lu-PSMA-617 for Progressive Metastatic CRPC

NCT03042468

Description:

The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Dose-escalation Study of Fractionated 177Lu-PSMA-617 for Progressive Metastatic CRPC
  • Official Title: Phase I/ll Dose-escalation Study of Fractionated Dose 177Lu-PSMA-617 for Progressive Metastatic Castration Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 1609017542
  • SECONDARY ID: PSMA-617
  • NCT ID: NCT03042468

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
177Lu-PSMA-617All subjects
68Ga-PSMA-HBED-CCAll subjects

Purpose

The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer.

Detailed Description

      Phase I dose escalation study with 177Lu-PSMA-617 using dose fractionation regimen will be
      performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu dose
      [100 mCi (3.7 GBq) - 600 mCi (22.2 GBq)] will be escalated in up to 6 different dose levels
      (3 + 3 study design). Additional 10 subjects will be enrolled at the MTD dose level to
      further assess safety and tolerability and to obtain a preliminary assessment of efficacy.
      The study will enroll adult males 18 years of age or older with documented progressive
      metastatic CRPC. The primary objectives are: - To determine the dose limiting toxicity (DLT)
      of fractionated dose of 177Lu-PSMA-617 - To determine the maximal tolerated and recommended
      phase II dose of 177Lu-PSMA-617 in a 2-week dose-fractionation regimen Subjects will receive
      the following study interventions:

        1. 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart
           (Visit 1 and 2)

        2. 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks
           with standard imaging Subjects will be on this study from screening to end of study (day
           85).

      The treatment phase comprises of 8 visits over 12 weeks. Patients will be followed until
      death for survival assessment. Patients removed from study for unacceptable adverse events
      will be followed until resolution or stabilization of the adverse event. All tests and
      procedures performed on this study are routine and standard of care except: 68Ga-PSMA-HBED-CC
      PET/CT scan, administration of investigational agent 177Lu-PSMA-617, research blood samples
      (CTCs for research, cell-free DNA sample), and PSMA testing on archive tissue.
    

Trial Arms

NameTypeDescriptionInterventions
All subjectsExperimental177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2) 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging
  • 177Lu-PSMA-617
  • 68Ga-PSMA-HBED-CC

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

          3. ECOG performance status of 0-2

          4. 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.

          5. 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)

          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:

               -  Absolute neutrophil count >2,000 cells/mm3

               -  Hemoglobin ≥9 g/dL (independent of transfusion and/or growth factors within 1
                  month prior to registration)

               -  Platelet count >150,000 x 109/uL (independent of transfusion and/or growth
                  factors within 3 months prior to randomization)

               -  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

          9. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Use of investigational drugs or implantation of investigational medical device ≤4
             weeks of Cycle 1, Day 1 or current enrollment in investigational drug or device study

          2. Prior systemic beta-emitting bone-seeking radioisotopes

          3. Brain metastases or leptomeningeal disease

          4. History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry

          5. 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

          6. Radiation therapy for treatment of PCa ≤4 weeks of Day 1 Cycle 1

          7. 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.

          8. 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

          9. 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.

         10. 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:Dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation will be used.
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:

Secondary Outcome Measures

Measure:The rate of PSA decline following fractionated 177Lu-PSMA-617, PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA.
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:
Measure:Radiographic response rate measured by RECIST 1.1 with PCWG3 modifications
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:
Measure:Radiographic progression-free survival measured by PCWG3 criteria
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:
Measure:Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:
Measure:Whole body distribution of 177Lu-PSMA-617 by performing planar/SPECT imaging of 177Lu-PSMA-617 at post-treatment follow up
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:
Measure:Radiation dosimetry of 177Lu-PSMA-617 and correlate toxicity with radiation dosimetry by performing planar/SPECT imaging of 177Lu-PSMA-617 at post-treatment follow up
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:
Measure:Biochemical and radiographic progression-free survival by PCWG3 criteria
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:
Measure:Overall survival following fractionated 177Lu-PSMA-617
Time Frame:at least 12 weeks of subsequent follow-up evaluations
Safety Issue:
Description:

Details

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

Last Updated

July 26, 2019