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

Overview

The primary objective of this study was to compare the two alternate primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) in patients with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA-617 in addition to best supportive/best standard of care (BSC/BSoC) versus patients treated with best supportive/best standard of care alone.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 27, 2021

Detailed Description

The study for each participant consisted of a Screening period, a Treatment period and a Follow-up period Screening and randomization During the screening period of up to 28 days before starting randomized treatment, each participant was assessed for PSMA positivity by gallium (68Ga) gozetotide imaging PET/scan per the pre-defined read rules, by the Sponsor's central reader. Only patients with PSMA-positive metastatic PC and meeting all other inclusion/exclusion criteria were randomized in a 2:1 ratio to receive either 177Lu-PSMA-617 plus BSC/BSoC or BSC/BSoC only. Randomized patients were stratified on the following factors: LDH level (=< or > 260 UI/L), presence of liver metastases (Yes or No), eastern cooperative oncology group (ECOG) score (0-1 or 2) and inclusion of NAAD in the BSC/BSoC (at time of randomization (Yes or No)). Protocol-specified BSC/BSoC for each patients was initiated by the investigating physician prior to patient randomization and maintained throughout the study. On-study changes to BSC/BSoC were allowed and at the discretion of the investigating physician.. Randomized treatment "Randomized treatment" in this study referred to 177Lu-PSMA-617+BSC/BSoC (investigational arm) and BSC/BSoC only (control arm). Patients randomized to the investigational arm began 177Lu-PSMA-617 administration within 28 days after randomization (C1D1). These patients received 7.4 gigabequerel (GBq) (+/- 10%) 177Lu-PSMA-617 once every 6 weeks (+/- 1 week) for a maximum of 6 cycles while receiving BSC/BSoC. After Cycle 4 treatment and prior to Cycle 5 treatment, the investigator assessed the following criteria to determine whether: – The patient showed evidence of response (i.e. radiological, PSA, clinical benefit) – The patient had signs of residual disease on CT with contrast/MRI or bone scan – The patient had shown good tolerance to the 177Lu-PSMA-617 treatment. If the patient met all of the criteria above and agreed to continue with additional treatment of 177Lu-PSMA-617, the Investigator could administer 2 additional cycles. A maximum of 6 cycles of 177Lu-PSMA-617 as allowed. If the patient did not meet any of the criteria or did not agree to additional 177Lu-PSMA-617 treatment, then no additional doses of 177Lu-PSMA-617 were administered after Cycle 4. After the last cycle of 177Lu-PSMA-617, patients continued to be treated with BSC/BSoC as long as the investigator felt they were clinically benefiting (regardless of radiographic progressive disease based on Investigator's assessment per PCWG3 criteria) or until they required a treatment regimen not allowed on this study. For both treatment arms, the cycle duration for Cycle 1-6 was 6 weeks and for Cycle 7 and beyond, was 12 weeks. From Cycle 7 onwards, all patients from both treatment arms only received BSC/BSoC. End of treatment The EOT visit was scheduled approximately 30 days after the last dose of 177Lu-PSMA-617 or the date of the BSC/BSoC EOT decision (whichever occurred later), but before the initiation of subsequent anti-cancer treatment, outside of what was allowed on study Long-term follow-up Patients who consented to be followed for long-term status updates, entered the long-term follow-up period after the EOT visit. The long-term follow-up included the collection of radiographic images (if a patient discontinued for reasons other than radiographic progression), OS, information about new treatments along with the patient's response to these treatments, AE assessment, and results of hematology and chemistry testing. During the follow-up, patients are contacted every 3 months (+/-1 month) via phone, email, or letter until the end of long-term the follow-up period (24 months after the first patient enters long-term follow-up) or until 508 deaths had occurred.

Interventions

  • Drug: 177Lu-PSMA-617
    • Administered intravenously once every 6 weeks (1 cycle) for a maximum of 6 cycles. After 4 cycles, patients were assessed for (1) evidence of response, (2) residual disease, and (3) tolerance to 177Lu-PSMA-617. If all 3 assessments were met the patient might received an additional 2 cycles of 177Lu-PSMA-617.
  • Other: Best supportive/best standard of care
    • Best supportive/best standard of care as defined by the local investigator

Arms, Groups and Cohorts

  • Experimental: 177Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)
    • Patients randomized to receive the investigational product received 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) might be used
  • Other: Best supportive/best standard of care (BS/BSOC) alone
    • Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator

Clinical Trial Outcome Measures

Primary Measures

  • Radiographic Progression-free Survival (rPFS)
    • Time Frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Radiographic progression-free survival (rPFS) was defined as the time (in months) from the date of randomization to the date of radiographic disease progression based on the central review assessment per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria or death due to any cause. Patients who were alive without radiographic progression at the analysis data cut-off were censored for rPFS at the time of their last evaluable radiographic assessment. Date of censoring for rPFS: 1) The censoring date was the date when the last evaluable radiographic assessment (CT/MRI/bone scan) determined a lack of progression; 2) If there were no evaluable assessments, censoring occurred at the date of randomization; 3) Patients who had 2 or more consecutive missed tumor assessments immediately prior to PD or death were censored at the date of the last evaluable tumor assessment prior to those missing tumor assessments.
  • Overall Survival (OS)
    • Time Frame: From date of randomization until date of death from any cause, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Overall Survival (OS) was defined as the time (in months) from the date of randomization to the date of death due to any cause. If the patient was not known to have died, then OS was censored. The censoring date was date of the last study visit, or contact, until the cut-off date. The cut-off date was not used for last contact date, unless the patient was seen or contacted on that date.

Secondary Measures

  • Number of Participants With Treatment Emergent Adverse Events
    • Time Frame: From randomization till 30 days safety follow-up, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • The distribution of adverse events (AE) was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs), through the monitoring of relevant clinical and laboratory safety parameters.
  • Overall Response Rate (ORR)
    • Time Frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR was based on RECIST 1.1 response for patients with measurable disease at baseline per central review assessment.
  • Disease Control Rate (DCR)
    • Time Frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Disease control rate (DCR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) according to RECIST v1.1 per central review assessment.
  • Duration of Response (DOR)
    • Time Frame: From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented radiographic progression or death due to any cause as per central review assessment.
  • Time to First Symptomatic Skeletal Event (SSE)
    • Time Frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Time to first Symptomatic Skeletal Event (SSE) was defined as the time (in months) from the date of randomization to the date of the SSE or death from any cause. The SSE date was the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurred first. SSE data for this endpoint were collected up through EOT visit. The censoring date was date of the last study visit (on or before the EOT visit).
  • Progression-free Survival (PFS)
    • Time Frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Progression-free survival (PFS) was defined as the time (in months) from the date of randomization to the date of first evidence of radiographic, clinical or PSA progression or death due to any cause, whichever occurred first.
  • Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Best percentage change from baseline in PSA level was defined as the maximum percent decrease at any time post-baseline, including only patients with a baseline value and at least one non-missing post-baseline value (scheduled and unscheduled).
  • Percentage of Participants Achieving Prostate-specific Antigen (PSA) Response
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • PSA response was defined as the proportion of patients who had a >= 50% decrease in PSA from baseline confirmed by a PSA measurement >= 4 weeks later.
  • Prostate-specific Antigen 80 (PSA80) Response
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • PSA80 response was defined as the proportion of participants who had a >= 80% decrease in PSA from baseline confirmed by a PSA measurement >= 4 weeks later.
  • Duration of PSA Response
    • Time Frame: From date of first documented PSA response till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Duration of PSA response was defined as the duration between the date of first document PSA response (i.e. >= 50% decrease in PSA from Baseline) and the earliest date of PSA progression, where date of PSA progression was defined as: 1) Where a decline from baseline was documented, date that a >= 25% increase in PSA and an absolute increase of 2 ng/mL or more from the nadir was documented and confirmed by a second consecutive value obtained at least 3 weeks later. Rises in PSA within the first 12 weeks of the date of first dose of randomized treatment were ignored; 2) Where no decline from baseline was documented, PSA progression was defined as a >= 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 weeks from the date of first dose of randomized treatment (without confirmation) as specified in the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines.
  • Best Percentage Change From Baseline in Alkaline Phosphatase (ALP) Level
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Best percentage change from baseline in alkaline phosphatase (ALP) level was defined as the maximum percent decrease at any time post-baseline, including only patients with a baseline value and at least one non-missing post-baseline value (scheduled and unscheduled).
  • Best Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Level
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Best percentage change from baseline in lactate dehydrogenase (LDH) level was defined as the maximum percent decrease at any time post-baseline, including only patients with a baseline value and at least one non-missing post-baseline value (scheduled and unscheduled).
  • Time to Worsening in BPI-SF Pain Intensity Scale
    • Time Frame: From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Time to worsening in BPI-SF pain intensity scale was defined as the time from randomization to the first occurring of an increase of worsening threshold (>=30% of baseline or >=2-point increase) at any time up through EOT visit compared to baseline, clinical disease progression, or death.
  • Time to Improvement After Worsening in BPI-SF Pain Intensity Scale
    • Time Frame: From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Time to improvement after worsening in BPI-SF pain intensity scale was defined as the time from worsening of Pain Intensity score to a Pain Intensity score <= baseline.
  • Time to Worsening in BPI-SF Pain Interference Scale
    • Time Frame: From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Time to worsening in BPI-SF pain interference scale was defined as the time from randomization to the first occurring of 1) an increase of worsening threshold (>=30% of baseline or >=2-point increase) at any time up through EOT visit compared to baseline, 2) clinical disease progression, or 3) death.
  • Time to Improvement After Worsening in BPI-SF Pain Interference Scale
    • Time Frame: From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Time to improvement after worsening in BPI-SF pain interference scale was defined as the time from worsening of Pain Interference score to a Pain Interference score <= baseline.
  • Time to Worsening in BPI-SF Worst Pain Intensity Scale (Time to Disease Related Pain)
    • Time Frame: From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Time to worsening in BPI-SF worst pain intensity scale (time to disease related pain) was defined as the time from randomization to the first occurring of worsening exceeding the threshold threshold (>=30% of baseline or >=2 point increase) at any time up through EOT visit compared to baseline, clinical disease progression, or death.
  • Change From Baseline in BPI-SF (Brief-Pain Inventory – Short Form) Pain Intensity Scale
    • Time Frame: Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)
    • The BPI-SF is a generic pain assessment tool used in research and practice for pain assessment in musculoskeletal conditions. The higher the BPI-SF score, the worse the pain. The BPI-SF consists of 4 questions regarding pain intensity (worst pain intensity, least pain intensity, average pain intensity and pain right now), 2 questions on the use of analgesics, and 7 questions on how the level pain has interfered with the subject’s life (General Activity, Mood, Walking Ability, Normal Work, Relations with other people, Sleep, Enjoyment of Life). Intensity items consist of an 11-response rating scale scored from 0 (“No Pain”) to 10 (“Pain As Bad As You Can Imagine”). BPI-SF Pain intensity is the mean of non-missing items of the 4 individual scales, if there are 3 or more items not missing; otherwise this scale is set to missing.
  • Change From Baseline in BPI-SF (Brief-Pain Inventory – Short Form) Pain Interference Scale
    • Time Frame: Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)
    • “The BPI-SF is a generic pain assessment tool used in research and practice for pain assessment in musculoskeletal conditions. The higher the BPI-SF score, the worse the pain. The BPI-SF consists of 4 questions regarding pain intensity (worst pain intensity, least pain intensity, average pain intensity and pain right now), 2 questions on the use of analgesics, and 7 questions on how the level pain has interfered with the subject’s life (General Activity, Mood, Walking Ability, Normal Work, Relations with other people, Sleep, Enjoyment of Life). Interference items consist of scores from 0 (“Does Not Interfere”) to 10 (“Completely Interferes”). BPI-SF Interference scale is the mean of non-missing items of the 7 items on pain interference, if there are 4 or more items not missing; otherwise this scale is set to missing.”
  • Time to Worsening in FACT-P Total Score
    • Time Frame: From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Time to worsening was defined as the time from randomization to the first occurring of a >=10 point decrease in FACT-P total score compared to baseline, clinical disease progression, or death.
  • Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy – Prostate) Total Score
    • Time Frame: Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)
    • The FACT-P total score (range 0-156) consist of five subscales (Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24)) and a functional well-being and prostate cancer subscale (range 0-48). Higher scores indicate higher degree of functioning and better quality of life.
  • Time to Worsening in EQ-5D-5L Utility Score
    • Time Frame: From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • Time to worsening for utility score was defined as time from randomization to the first occurrence of worsening in utility score relative to baseline (no change or any decrease), clinical disease progression, or death.
  • Change From Baseline in the European Quality of Life (EuroQol) – 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score
    • Time Frame: Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)
    • The EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3=moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions. A utility score was obtained by using a weighted combination of the levels of the five dimension-scales. The weights were based on value sets which were country-specific for the U.K. Utility scores ranges from the lowest possible score for a living patient of -0.594 (when all responses are ‘5’) to 1 (when all responses are ‘1’).If a patient died, he was assigned a score of 0 on the date of death.
  • Change From Baseline in the European Quality of Life (EuroQol) – 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS
    • Time Frame: Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)
    • The EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ VAS records the patient’s self-rated health on a vertical visual analogue 0-100 scale, where the endpoints are labelled ‘The best health you can imagine’ and ‘The worst health you can imagine’. The higher the EQ-VAS score, the better the QoL.
  • Number of Participants Hospitalized as In-patient
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • The number of hospitalizations (yes/no) (admitted as in-patient) was collected as part of the hospital admission for health economic evaluations.
  • Duration of Time in Hospital Following 177Lu-PSMA-617 Administration
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • The duration of time in hospital following 177Lu-PSMA-617 administration (hours) was the time span of patient discharged as captured on the 177Lu-PSMA-617 administration Case Report Form (CRF).
  • Concomitant Drug Use for Health Economics Analysis
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • The list of concomitant drugs as captured on the concomitant medication/therapy CRF page to include in each category was pre-specified and flagged prior to the pre planned analyses. (1) Bisphosphonates (including but not limited to zoledronic acid, alendronic acid, etc.), denosumab, and other bone targeted therapies), (2) Corticosteroids for systemic use (3), Antifungals for systemic use (i.e. ketoconazole), (4) ESA (erythropoietin stimulating agents, i.e. epoetin alfa), (5) Granulocyte macrophage colony-stimulating factor (GM-CSF), (6) Novel androgen axis drugs (NAADs; i.e. enzalutamide, abiraterone, apalutamide), (7) Antiemetics and (8) Opioid analgesics use for cancer-related pain.
  • Therapeutic Interventions for Health Economics Analysis
    • Time Frame: From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)
    • The list of therapeutic interventions was pre-specified and flagged prior to the pre planned analyses as captured on: 1) the concurrent radiotherapy CRF page to include local external beam radiotherapy (inclusive of palliative external radiation), 2) on the concomitant medication/therapy CRF page to include blood transfusion (full blood or derivates).

Participating in This Clinical Trial

Inclusion Criteria

1. Patients must have the ability to understand and sign an approved informed consent form (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 Eastern Cooperative Oncology Group (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 be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive, and eligible as determined by the sponsor's central reader. 8. Patients must have a castrate level of serum/plasma 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: a. The patient's physician deems him unsuitable to receive a second taxane regimen (e.g. frailty assessed by geriatric or health status evaluation, intolerance, etc.). 11. Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria: 1. Serum/plasma 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: a. Bone marrow reserve:

  • White blood cell (WBC) count >= 2.5 x 10^9/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) b. 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 c. Renal: – Serum/plasma 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) [Inclusion #16 has been removed] 17. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial. 18. For patients who have partners of childbearing potential: 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 6 months after last study drug administration. 19. The best standard of care/ best supportive care options planned for this patient: 1. Are allowed by the protocol 2. Have been agreed to by the treating investigator and patient 3. Allow for the management of the patient without 177Lu-PSMA-617 Exclusion Criteria:

1. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. 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 for the sole purpose of making a subject eligible for study inclusion. 7. Patients with a history of Central Nervous System (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, known 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. However, patients with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, superficial bladder cancer.

Gender Eligibility: Male

Prostate cancer

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Endocyte
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals

References

Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):38-52. doi: 10.1038/s41391-019-0174-x. Epub 2019 Oct 8. Review.

Citations Reporting on Results

Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Pérez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. doi: 10.1056/NEJMoa2107322. Epub 2021 Jun 23.

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