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

• ClinicalTrials.gov Identifier: NCT03511664
• Recruitment Status: Completed
• First Posted: April 30, 2018
• Results First Posted: May 9, 2022
• Last Update Posted: January 31, 2024
• Sponsor: Endocyte
• Information provided by (Responsible Party): Endocyte

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: 177Lu-PSMA-617; Other: Best supportive/best standard of care	Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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 patient 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 gigabecquerel (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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 831 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The study population included patients with progressive PSMA-positive mCRPC who received at least one novel androgen axis drug [NAAD] (such as enzalutamide or abiraterone) and were previously treated with 1 to 2 taxane containing regimens. Patients treated with only 1 prior taxane regimen were eligible if the patient was unwilling or the patient's physician deemed the patient unsuitable to receive a second regimen.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 29, 2018
• Actual Primary Completion Date: January 27, 2021
• Actual Study Completion Date: December 13, 2023

Arms and Interventions

Arm	Intervention/treatment
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	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
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	Other: Best supportive/best standard of care; Best supportive/best standard of care as defined by the local investigator

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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 Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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).
6. 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.
7. 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).
8. 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.
9. 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.
10. 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.
11. 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).
12. 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).
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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).
27. 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.
28. 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Prostate cancer
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

HonorHealth Research Institute

Scottsdale, Arizona, United States, 85258

University of Arizona Cancer Center

Tucson, Arizona, United States, 85719-1454

United States, California

VA Greater Los Angeles Healthcare System

Los Angeles, California, United States, 90073

University of California Los Angeles, Nuclear Medicine

Los Angeles, California, United States, 90095

Stanford Cancer Institute

Palo Alto, California, United States, 94305

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94158

United States, Colorado

University of Colorado Hospital

Aurora, Colorado, United States, 80045

United States, Connecticut

Yale Cancer Center

New Haven, Connecticut, United States, 06520-8028

United States, District of Columbia

Washington DC VA Medical Center, Nuclear Medicine Service

Washington, District of Columbia, United States, 20422

United States, Florida

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States, 33612

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Indiana

Parkview Research Center

Fort Wayne, Indiana, United States, 46845

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States, 46202

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

Iowa City VA Medical Center

Iowa City, Iowa, United States, 52246

United States, Kentucky

Norton Cancer Institute

Louisville, Kentucky, United States, 40202

United States, Louisiana

Tulane Medical Center, Tulane Cancer Center

New Orleans, Louisiana, United States, 70112

United States, Maryland

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States, 21201

Chesapeake Urology Associates (CUA) P.A.

Towson, Maryland, United States, 21204

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215-5450

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

United States, Michigan

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, United States, 48105

University of Michigan Hospitals

Ann Arbor, Michigan, United States, 48109

Karmanos Cancer Center

Detroit, Michigan, United States, 48201

United States, Minnesota

Mayo Clinic - Rochester

Rochester, Minnesota, United States, 55905

United States, Missouri

Saint Louis University Hospital

Saint Louis, Missouri, United States, 63104

VA St. Louis Health Care System - John Cochran

Saint Louis, Missouri, United States, 63106

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110-1093

United States, Nebraska

XCancer Omaha / Urology Cancer Center

Omaha, Nebraska, United States, 68130

United States, Nevada

Comprehensive Cancer Centers of Nevada - Twain Office

Las Vegas, Nevada, United States, 89169

United States, New Jersey

Regional Cancer Care Associates, Central Jersey Division

East Brunswick, New Jersey, United States, 08816

United States, New Mexico

New Mexico Oncology Hematology Consultants Ltd., New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87109

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

New York Presbyterian Hospital/Weill Cornell Medical Center

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center, Duke Cancer Center

Durham, North Carolina, United States, 27710

United States, Ohio

Greater Dayton Cancer Center

Kettering, Ohio, United States, 45409

United States, Oregon

Oregon Health and Science University, Nuclear Medicine

Portland, Oregon, United States, 97239-3098

United States, Pennsylvania

Pennsylvania Cancer Specialists & Research Institute

Gettysburg, Pennsylvania, United States, 17325

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States, 19107

United States, South Carolina

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States, 29572

United States, Texas

VA North Texas Health Care System, Nuclear Medicine Service

Dallas, Texas, United States, 75216

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

Excel Diagnostics & Nuclear Oncology Center

Houston, Texas, United States, 77042

United States, Virginia

Emily Couric Clinical Cancer Center

Charlottesville, Virginia, United States, 22903

United States, Washington

Swedish Cancer Institute Research

Seattle, Washington, United States, 98104

Belgium

Jules Bordet Institute

Brussels, Belgium

Saint Luc University Hospital

Brussels, Belgium

University Hospitals Leuven, Campus Gasthuisberg, Department of Nuclear Medicine

Leuven, Belgium

Canada, British Columbia

BC Cancer - Vancouver

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Ontario

London Health Sciences Centre, Division of Nuclear Medicine

London, Ontario, Canada, N6A 4L6

Ottawa Hospital, Cancer Center

Ottawa, Ontario, Canada, K1H 8L6

Sunnybrook Research Institute, Odette Cancer Center

Toronto, Ontario, Canada, M4N 3M5

Canada, Quebec

CHUM - University Hospital of Montreal

Montreal, Quebec, Canada, H2X 3E4

Jewish General Hospital

Montreal, Quebec, Canada, H3T 1E2

Canada

CHU of Quebec - Laval University

Quebec, Canada, G1R 2J6

Denmark

Aalborg University Hospital, Oncology Department

Aalborg, Denmark

Aarhus University Hospital, Department of Oncology

Aarhus, Denmark

Rigshospitalet - University Hospital Copenhagen, Department of Oncology

Copenhagen, Denmark

France

Bergonie Institute

Bordeaux, France

Center Jean Perrin

Clermont-Ferrand, France

Leon Berard Center

Lyon, France

Saint-Louis Hospital

Paris, France

Tenon Hospital

Paris, France

Institute Claudius Regaud, Toulouse Cancer Research Center

Toulouse, France

Gustave Roussy Oncology Institute

Villejuif, France

Germany

University Hospital Essen, Clinic for Nuclear Medicine

Essen, Germany

University Hospital Muenster, Department of Nuclear Medicine

Muenster, Germany

Hospital rechts der Isar, Department of Nuclear Medicine

Munich, Germany

Rostock University Medical Center, Clinic and Polyclinic for Nuclear Medicine

Rostock, Germany

Netherlands

The Netherlands Cancer Institute

Amsterdam, Netherlands

St. Antonius Hospital

Nieuwegein, Netherlands

Radboud University Medical Center (Radboudumc)

Nijmegen, Netherlands

UMC Utrecht

Utrecht, Netherlands

Puerto Rico

VA Caribbean Healthcare System

San Juan, Puerto Rico, 00921

Sweden

Sahlgrenska University Hospital, Department of Oncology

Gothenburg, Sweden

Skane University Hospital - Barngatan, Clinical Trials Unit

Lund, Sweden

Karolinska University Hospital

Stockholm, Sweden

Norrlands University Hospital, Cancer Center

Umea, Sweden

Uppsala University Hospital, Department of Oncology

Uppsala, Sweden

United Kingdom

Bristol Hematology & Oncology Center

Bristol, United Kingdom

Beatson West of Scotland Cancer Center

Glasgow, United Kingdom

Royal Surrey County Hospital

Guildford, United Kingdom

Guy's Hospital

London, United Kingdom

Royal Free Hospital

London, United Kingdom

St Bartholomew's Hospital

London, United Kingdom

University College London Hospitals NHS Foundation Trust

London, United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Institute of Cancer Research

Sutton, United Kingdom

Sponsors and Collaborators

Endocyte

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Endocyte:

Study Protocol  [PDF] April 26, 2021

Statistical Analysis Plan  [PDF] January 18, 2021

More Information

Publications of 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. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. PMID:34161051

Other Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Perez-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.

Sundlov A, Sjogreen-Gleisner K. Peptide Receptor Radionuclide Therapy - Prospects for Personalised Treatment. Clin Oncol (R Coll Radiol). 2021 Feb;33(2):92-97. doi: 10.1016/j.clon.2020.10.020. Epub 2020 Nov 12.

• Responsible Party: Endocyte
• ClinicalTrials.gov Identifier: NCT03511664
• Other Study ID Numbers: PSMA-617-01; 2018-000459-41 ( EudraCT Number ); CAAA617A12301 ( Other Identifier: Novartis )
• First Posted: April 30, 2018
• Results First Posted: May 9, 2022
• Last Update Posted: January 31, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Endocyte:

Metastatic castration-resistant prostate cancer; mCRPC; 177Lu-PSMA-617; PSMA-617; PSMA-11; radioligand therapy

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Pluvicto; Radiopharmaceuticals; Molecular Mechanisms of Pharmacological Action