Clinical Trials /

Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer

NCT03511664

Description:

The primary objective of this study is to compare overall survival (OS) in patients with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/best standard of care versus patients treated with best supportive/best standard of care alone. Key secondary objectives are an arm-to-arm comparison of the following: - Radiographic progression-free survival (rPFS) - Response Evaluation Criteria in Solid Tumors (RECIST) response - Time to a first symptomatic skeletal event (SSE) Additional Secondary Objectives: - Safety and tolerability of 177Lu-PSMA-617 - Health-related quality of life (HRQoL; EQ-5D-5L, FACT-P and Brief Pain Inventory - Short Form (BPI-SF)) - Health economics - Progression-free survival (PFS) (radiographic, clinical, or prostate-specific antigen [PSA] progression-free survival) - Biochemical response as measured by PSA. Alkaline phosphatase [ALP] levels and lactate dehydrogenase [LDH] levels will also be measured.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer
  • Official Title: VISION: An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)

Clinical Trial IDs

  • ORG STUDY ID: PSMA-617-01
  • NCT ID: NCT03511664

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
177Lu-PSMA-617177Lu-PSMA-617 plus BS/BSC

Purpose

The primary objective of this study is to compare overall survival (OS) in patients with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/best standard of care versus patients treated with best supportive/best standard of care alone. Key secondary objectives are an arm-to-arm comparison of the following: - Radiographic progression-free survival (rPFS) - Response Evaluation Criteria in Solid Tumors (RECIST) response - Time to a first symptomatic skeletal event (SSE) Additional Secondary Objectives: - Safety and tolerability of 177Lu-PSMA-617 - Health-related quality of life (HRQoL; EQ-5D-5L, FACT-P and Brief Pain Inventory - Short Form (BPI-SF)) - Health economics - Progression-free survival (PFS) (radiographic, clinical, or prostate-specific antigen [PSA] progression-free survival) - Biochemical response as measured by PSA. Alkaline phosphatase [ALP] levels and lactate dehydrogenase [LDH] levels will also be measured.

Detailed Description

      Patients with PSMA positive scans will be randomized in a 2:1 ratio to receive either
      177Lu-PSMA-617 plus best supportive/best standard of care or to receive best supportive/best
      standard of care only. Best supportive/best standard of care will be determined by the
      treating physician/investigator but will exclude investigational agents, cytotoxic
      chemotherapy, other systemic radioisotopes, and hemi-body radiotherapy. Novel androgen axis
      drugs [NAADs] (such as abiraterone or enzalutamide) are allowed.

      The study is open-label and patients will be monitored throughout the 6 to 10-month treatment
      period for survival, disease progression, and adverse events.

      A long-term follow-up period will include the collection of survival and treatment updates,
      adverse events assessment, as well as blood for hematology and chemistry testing. During
      follow-up, patients will be contacted every 3 months (±1 month) via phone, email, or letter
      for 24 months or until the the overall censoring rate for survival reduces to a level
      identified in the SAP.

      An End of Treatment visit should occur once a patient is to enter the long term follow up.
      This visit should occur approximately 30 days from the last dose of 177Lu-PSMA-617 or best
      supportive/best standard of care, but before the initiation of subsequent anti-cancer
      treatment, outside of what is allowed on study.

      The planned enrollment for this study is 750 patients.
    

Trial Arms

NameTypeDescriptionInterventions
177Lu-PSMA-617 plus BS/BSCExperimentalPatients randomized to receive the investigational product will receive 7.4 GBq (±10%) 177Lu-PSMA-617 intravenously every 6 weeks (±1 week) for a maximum of 6 cycles. + Best supportive/best standard of care (BS/BSOC)
  • 177Lu-PSMA-617
BS/BSC aloneOtherPatients randomized to this arm will receive best supportive/best standard of care (BS/BSOC) as determined by the investigator

    Eligibility Criteria

            Inclusion Criteria:
    
              -  To qualify for enrollment, patients must meet the following criteria:
    
                   1. Patients must have the ability to understand and sign an approved ICF.
    
                   2. Patients must have the ability to understand and comply with all protocol
                      requirements.
    
                   3. Patients must be ≥18 years of age.
    
                   4. Patients must have an ECOG performance status of 0 to 2.
    
                   5. Patients must have a life expectancy >6 months.
    
                   6. Patients must have histological, pathological, and/or cytological confirmation of
                      prostate cancer.
    
                   7. Patients must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the
                      sponsor's central reader.
    
                   8. Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy
                      and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
    
                   9. Patients must have received at least one NAAD (such as enzalutamide and/or
                      abiraterone).
    
                  10. Patients must have been previously treated with at least 1, but no more than 2
                      previous taxane regimens. A taxane regimen is defined as a minimum exposure of 2
                      cycles of a taxane. If a patient has received only 1 taxane regimen, the patient
                      is eligible if:
    
                        1. The patient is not willing to receive a second taxane regimen, or
    
                        2. The patient's physician deems him unsuitable to receive a second taxane
                           regimen (e.g. frailty assessed by geriatric or health status evaluation or
                           intolerance).
    
                  11. Patients must have progressive mCRPC. Documented progressive mCRPC will be based
                      on at least 1 of the following criteria:
    
                        1. Serum PSA progression defined as 2 consecutive increases in PSA over a
                           previous reference value measured at least 1 week prior. The minimal start
                           value is 2.0 ng/mL.
    
                        2. Soft-tissue progression defined as an increase ≥20% in the sum of the
                           diameter (SOD) (short axis for nodal lesions and long axis for non-nodal
                           lesions) of all target lesions based on the smallest SOD since treatment
                           started or the appearance of one or more new lesions.
    
                        3. Progression of bone disease: evaluable disease or new bone lesions(s) by
                           bone scan (2+2 PCWG3 criteria, Scher et al 2016).
    
                  12. Patients must have≥ 1 metastatic lesion that is present on baseline CT, MRI, or
                      bone scan imaging obtained ≤28 days prior to beginning study therapy.
    
                  13. Patients must have recovered to ≤ Grade 2 from all clinically significant
                      toxicities related to prior therapies (i.e. prior chemotherapy, radiation,
                      immunotherapy, etc.).
    
                  14. Patients must have adequate organ function:
    
                        1. Bone marrow reserve:
    
                             -  White blood cell (WBC) count ≥2.5 x 109/L (2.5 x 10^9/L is equivalent
                                to 2.5 x 10^3/µL and 2.5 x K/µL and 2.5 x 10^3/cumm and 2500/µL) OR
                                absolute neutrophil count (ANC) ≥1.5 x 10^9/L (1.5 x 10^9/L is
                                equivalent to 1.5 x 10^3/µL and 1.5 x K/µL and 1.5 x 10^3/cumm and
                                1500/µL)
    
                             -  Platelets≥ 100 x 10^9/L (100 x 10^9/L is equivalent to 100 x 10^3/µL
                                and 100 x K/µL and 100 x 10^3/cumm and 100,000/µL)
    
                             -  Hemoglobin≥ 9 g/dL (9 g/dL is equivalent to 90 g/L and 5.59 mmol/L)
    
                        2. Hepatic:
    
                             -  Total bilirubin ≤1.5 x the institutional upper limit of normal (ULN).
                                For patients with known Gilbert's Syndrome ≤ 3 x ULN is permitted
    
                             -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0
                                x ULN OR ≤5.0 x ULN for patients with liver metastases
    
                        3. Renal:
    
                             -  Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min
    
                  15. Albumin >3.0 g/dL (3.0 g/dL is equivalent to 30 g/L)
    
                  16. Patients on a stable bisphosphonate or denosumab regimen for ≥30 days prior to
                      randomization are eligible.
    
                  17. HIV-infected patients who are healthy and have a low risk of AIDS-related
                      outcomes are included in this trial.
    
                      For patients who have partners of childbearing potential:
    
                  18. Partner and/or patient must use a method of birth control with adequate barrier
                      protection, deemed acceptable by the principle investigator during the study and
                      for 3 months after last study drug administration.
    
            Exclusion Criteria:
    
              -  Patients who meet any of the following criteria will be excluded from the study:
    
                   1. Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188,
                      Radium-223 or hemi-body irradiation within 6 months prior to randomization.
                      Previous PSMA-targeted radioligand therapy is not allowed.
    
                   2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological
                      therapy [including monoclonal antibodies]) within 28 days prior to day of
                      randomization.
    
                   3. Any investigational agents within 28 days prior to day of randomization.
    
                   4. Known hypersensitivity to the components of the study therapy or its analogs.
    
                   5. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or
                      investigational therapy.
    
                   6. Transfusion within 30 days of randomization.
    
                   7. Patients with a history of CNS metastases must have received therapy (surgery,
                      radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not
                      receiving corticosteroids for the purposes of maintaining neurologic integrity.
                      Patients with epidural disease, canal disease and prior cord involvement are
                      eligible if those areas have been treated, are stable, and not neurologically
                      impaired. For patients with parenchymal CNS metastasis (or a history of CNS
                      metastasis), baseline and subsequent radiological imaging must include evaluation
                      of the brain (MRI preferred or CT with contrast).
    
                   8. A superscan as seen in the baseline bone scan.
    
                   9. Symptomatic cord compression, or clinical or radiologic findings indicative of
                      impending cord compression.
    
                  10. Concurrent serious (as determined by the Principal Investigator) medical
                      conditions, including, but not limited to, New York Heart Association class III
                      or IV congestive heart failure, history of congenital prolonged QT syndrome,
                      uncontrolled infection, active hepatitis B or C, or other significant co-morbid
                      conditions that in the opinion of the investigator would impair study
                      participation or cooperation.
    
                  11. Diagnosed with other malignancies that are expected to alter life expectancy or
                      may interfere with disease assessment. Patients with adequately treated
                      non-melanoma skin cancer, superficial bladder cancer and patients with prior
                      history of malignancy who have been disease free for more than 3 years are
                      eligible.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Male
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Survival
    Time Frame:Every 6-8 weeks until end of treatment and every 3 months during long term follow up [up to 24 months
    Safety Issue:
    Description:Overall survival (OS) in patients with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/standard of care

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Endocyte

    Trial Keywords

    • mCRPC
    • 177Lu-PSMA-617
    • PSMA-617
    • PSMA-11
    • radioligand therapy

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