Clinical Trials /

177Lu−J591 and 177Lu−PSMA−617 Combination for mCRPC

NCT03545165

Description:

Phase I dose escalation study with combination of 177Lu−J591 and 177Lu−PSMA−617 using a dose-fractionated regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu−J591 dose for each subject will be 2.7 GBq/m2 (73 mCi/m2) of 177Lu with 20 mg J591 and the cumulative 177Lu−PSMA−617 dose for each subject will vary (depending on the Cohort) from 3.7 GBq (100 mCi) to 18.5 GBq (500 mCi). The 177Lu−PSMA−617 dose will be escalated in up to 6 different dose levels (3+3 dose−escalation study / de-escalation design). For the phase II portion, a minimum number of 14 patients will be enrolled at MTD (including those enrolled at MTD in Phase I) and a maximum of 24.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 177Lu−J591 and 177Lu−PSMA−617 Combination for mCRPC
  • Official Title: Phase I/II Dose−Escalation Trial of Combination Fractionated-dose 177Lu−J591 and 177Lu−PSMA−617 in Patients With Metastatic Castration−Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 1802018988
  • NCT ID: NCT03545165

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
177Lu−PSMA−617All Subjects
177Lu−J591All Subjects
68Ga−PSMA−HBED−CCAll Subjects

Purpose

Phase I dose escalation study with combination of 177Lu−J591 and 177Lu−PSMA−617 using a dose-fractionated regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu−J591 dose for each subject will be 2.7 GBq/m2 (73 mCi/m2) of 177Lu with 20 mg J591 and the cumulative 177Lu−PSMA−617 dose for each subject will vary (depending on the Cohort) from 3.7 GBq (100 mCi) to 18.5 GBq (500 mCi). The 177Lu−PSMA−617 dose will be escalated in up to 6 different dose levels (3+3 dose−escalation study / de-escalation design). For the phase II portion, a minimum number of 14 patients will be enrolled at MTD (including those enrolled at MTD in Phase I) and a maximum of 24.

Detailed 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 combination of
      177Lu−J591 and 177Lu−PSMA−617 in a two−week dose−fractionation regimen. 177Lu−J591 will be
      given at a moderate dose previously demonstrated to be safe x2 infusions two weeks apart. For
      177Lu−PSMA−617 the dose escalation will start at 3.7 GBq (100 mCi) and escalate in increments
      of 1.85 GBq (50 mCi) for each dose to a planned maximum of 9.25 GBq (250 mCi) x2 doses, 2
      weeks apart. Should there be unacceptable toxicity at the initial dose level, we will
      de-escalate to dose level -1 (1.85 GBq / 50 mCi per dose). After the phase I study has
      established a MTD, the Phase II, single-arm trial will start.

      Patients must have documented progressive metastatic CRPC disease based on Prostate Cancer
      Working Group 3 (PCWG3) criteria in order to be eligible for enrollment. Upon meeting the
      inclusion and exclusion criteria and signing the informed consent and HIPPA form, subjects
      will undergo the screening. As part of the screening, subjects will get a single dose of
      68Ga−PSMA−HBED−CC and will have a PET/CT. Nuclear Medicine physician(s) will review the
      PET/CT scans to document PSMA expression at tumor site(s).

      Subjects will have Lutetium−177 Planar/SPECT Imaging on Day 8 (±1 day) after the first dose
      of 177Lu−J591 + 177Lu−PSMA−617. Optimal images will be performed on selected consenting
      subjects between the initial treatment visit #1 on Day 1 and Day 4 and prior to treatment
      visit #2 on D15 ±1. Subjects will be closely monitored for AEs (weekly x2 weeks, then every 2
      weeks for one month, at 8 and 12 weeks, and then every 4 weeks for next 3 months).

      Upon completion of investigational treatment with dose−fractionation regimen of the
      combination of 177Lu−J591 + 177Lu−PSMA−617, 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.

      .
    

Trial Arms

NameTypeDescriptionInterventions
All SubjectsExperimental177Lu−PSMA−617 [1.85 GBq (50 mCi) - 9.25 GBq (250 mCi)] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration 177Lu−J591 [1.35 GBq/m2 or 36.5 mCi/m2] x2 doses, 2 weeks apart (Treatment Visit #1 and #2), IV administration 68Ga−PSMA−HBED−CC [185 ±74 MBq or 5 ±2 mCi] intravenous during screening and at 12 weeks (±1 week) with standard imaging
  • 177Lu−PSMA−617
  • 177Lu−J591
  • 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:

             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/GnRH analogue (agonist/antagonist) if they have not undergone
             bilateral 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

               -  Platelet count >150,000 x 109/L

               -  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)

          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 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 Treatment visit # 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 Treatment
             visit #1

          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 Treatment visit #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:Dose limiting toxicity (DLT) of combination therapy in a 2−week dose−fractionation regimen
Time Frame:Approximately 3 months after enrollment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Radiographic response rate by RECIST 1.1 with PCWG3 modifications
Time Frame:At the efficacy (scan) visit time point (12 weeks)
Safety Issue:
Description:
Measure:Biomedical progression−free survival by PCWG3 criteria
Time Frame:At the efficacy (scan) visit time point (12 weeks)
Safety Issue:
Description:
Measure:Radiographic progression−free survival by PCWG3 criteria
Time Frame:At the efficacy (scan) visit time point (12 weeks)
Safety Issue:
Description:
Measure:Overall survival following treatment with the combination of 177Lu−J591 and 177Lu−PSMA−617 in a 2−week dose−fractionation regimen
Time Frame:Approximately 3 months after enrollment until study completion, approximately 36 months, or death
Safety Issue:
Description:
Measure:Safety of treatment with the combination of 177Lu−J591 and 177Lu−PSMA−617 in a 2−week dose−fractionation regimen as assessed by CTCAE 4.0
Time Frame:Up to 6 months after first treatment
Safety Issue:
Description:
Measure:Changes in CTC count as measured by CellSearch
Time Frame:At the efficacy (scan) visit time point (12 weeks)
Safety Issue:
Description:
Measure:Rate of favorable CTC count as measured by Cell Search
Time Frame:At the efficacy (scan) visit time point (12 weeks)
Safety Issue:
Description:
Measure:Rate of favorable LDH count
Time Frame:During treatment phase, then every 4 weeks until radiographic progression, assessed up to 6 months
Safety Issue:
Description:
Measure:Patient reported outcomes using FACT−P
Time Frame:During treatment phase, then every 12 weeks until radiographic progression, assessed up to 6 months
Safety Issue:
Description:
Measure:Patient reported outcome using the Brief Pain Inventory short form
Time Frame:During treatment phase, then every 12 weeks until radiographic progression, assessed up to 6 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Weill Medical College of Cornell University

Last Updated

July 26, 2019