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

Phase 3

Completed

• Conditions: Prostate Cancer
• Interventions: Drug: 177Lu-PSMA-617; Other: Best supportive/best standard of care

• Registration Number: NCT03511664
• Lead Sponsor: Endocyte

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.

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 Timeline

• Study First Submitted: 2018-04-13
• Study First Submitted QC: 2018-04-26
• Study First Posted: 2018-04-30
• Study Start: 2018-05-29
• Primary Completion: 2021-01-27
• Disposition First Submitted: 2021-12-01
• Disposition First Submitted QC: 2021-12-06
• Disposition First Posted: 2021-12-08
• Results First Submitted: 2022-04-12
• Results First Submitted QC: 2022-04-12
• Results First Posted: 2022-05-09
• Study Completion: 2023-12-14
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-09
• Last Update Posted: 2024-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 831

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]

16. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial.

17. 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.

18. The best standard of care/ best supportive care options planned for this patient:

19. Are allowed by the protocol

20. Have been agreed to by the treating investigator and patient

21. Allow for the management of the patient without 177Lu-PSMA-617

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
177Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)	Best supportive/best standard of care	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
Best supportive/best standard of care (BS/BSOC) alone	Best supportive/best standard of care	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
177Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC)	177Lu-PSMA-617	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

Primary Outcome Measures

Name	Time	Method
Radiographic Progression-free Survival (rPFS)	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)	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

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events	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)	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)	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)	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)	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)	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	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).
Number of Participants Hospitalized as In-patient	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	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	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	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).
Percentage of Participants Achieving Prostate-specific Antigen (PSA) Response	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	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	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	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	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	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	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	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	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)	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	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	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	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	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	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	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	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.

Trial Locations

Locations (88)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Indiana University Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Sunnybrook Research Institute, Odette Cancer Center; 🇨🇦 Toronto, Ontario, Canada

University Hospital Muenster, Department of Nuclear Medicine; 🇩🇪 Muenster, Germany

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

Mayo Clinic - Rochester; 🇺🇸 Rochester, Minnesota, United States

XCancer Omaha / Urology Cancer Center; 🇺🇸 Omaha, Nebraska, United States

VA Greater Los Angeles Healthcare System; 🇺🇸 Los Angeles, California, United States

University of California Los Angeles, Nuclear Medicine; 🇺🇸 Los Angeles, California, United States

Parkview Research Center; 🇺🇸 Fort Wayne, Indiana, United States

Iowa City VA Medical Center; 🇺🇸 Iowa City, Iowa, United States

University of Maryland Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Chesapeake Urology Associates (CUA) P.A.; 🇺🇸 Towson, Maryland, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Center; 🇺🇸 Detroit, Michigan, United States

Saint Louis University Hospital; 🇺🇸 Saint Louis, Missouri, United States

Regional Cancer Care Associates, Central Jersey Division; 🇺🇸 East Brunswick, New Jersey, United States

Comprehensive Cancer Centers of Nevada - Twain Office; 🇺🇸 Las Vegas, Nevada, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Oregon Health and Science University, Nuclear Medicine; 🇺🇸 Portland, Oregon, United States

Greater Dayton Cancer Center; 🇺🇸 Kettering, Ohio, United States

Duke University Medical Center, Duke Cancer Center; 🇺🇸 Durham, North Carolina, United States

Pennsylvania Cancer Specialists & Research Institute; 🇺🇸 Gettysburg, Pennsylvania, United States

Carolina Urologic Research Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Excel Diagnostics & Nuclear Oncology Center; 🇺🇸 Houston, Texas, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Emily Couric Clinical Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

Jules Bordet Institute; 🇧🇪 Brussels, Belgium

Swedish Cancer Institute Research; 🇺🇸 Seattle, Washington, United States

BC Cancer - Vancouver; 🇨🇦 Vancouver, British Columbia, Canada

Saint Luc University Hospital; 🇧🇪 Brussels, Belgium

University Hospitals Leuven, Campus Gasthuisberg, Department of Nuclear Medicine; 🇧🇪 Leuven, Belgium

Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada

CHUM - University Hospital of Montreal; 🇨🇦 Montreal, Quebec, Canada

London Health Sciences Centre, Division of Nuclear Medicine; 🇨🇦 London, Ontario, Canada

Aalborg University Hospital, Oncology Department; 🇩🇰 Aalborg, Denmark

Aarhus University Hospital, Department of Oncology; 🇩🇰 Aarhus, Denmark

Center Jean Perrin; 🇫🇷 Clermont-Ferrand, France

Saint-Louis Hospital; 🇫🇷 Paris, France

Institute Claudius Regaud, Toulouse Cancer Research Center; 🇫🇷 Toulouse, France

Gustave Roussy Oncology Institute; 🇫🇷 Villejuif, France

University Hospital Essen, Clinic for Nuclear Medicine; 🇩🇪 Essen, Germany

Hospital rechts der Isar, Department of Nuclear Medicine; 🇩🇪 Munich, Germany

The Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands

Rostock University Medical Center, Clinic and Polyclinic for Nuclear Medicine; 🇩🇪 Rostock, Germany

St. Antonius Hospital; 🇳🇱 Nieuwegein, Netherlands

VA Caribbean Healthcare System; 🇵🇷 San Juan, Puerto Rico

Radboud University Medical Center (Radboudumc); 🇳🇱 Nijmegen, Netherlands

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

Beatson West of Scotland Cancer Center; 🇬🇧 Glasgow, United Kingdom

Bristol Hematology & Oncology Center; 🇬🇧 Bristol, United Kingdom

Uppsala University Hospital, Department of Oncology; 🇸🇪 Uppsala, Sweden

Royal Free Hospital; 🇬🇧 London, United Kingdom

University College London Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom

St Bartholomew's Hospital; 🇬🇧 London, United Kingdom

Institute of Cancer Research; 🇬🇧 Sutton, United Kingdom

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Rigshospitalet - University Hospital Copenhagen, Department of Oncology; 🇩🇰 Copenhagen, Denmark

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States

New Mexico Oncology Hematology Consultants Ltd., New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

VA North Texas Health Care System, Nuclear Medicine Service; 🇺🇸 Dallas, Texas, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Stanford Cancer Institute; 🇺🇸 Palo Alto, California, United States

Washington DC VA Medical Center, Nuclear Medicine Service; 🇺🇸 Washington, District of Columbia, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

VA St. Louis Health Care System - John Cochran; 🇺🇸 Saint Louis, Missouri, United States

New York Presbyterian Hospital/Weill Cornell Medical Center; 🇺🇸 New York, New York, United States

Ottawa Hospital, Cancer Center; 🇨🇦 Ottawa, Ontario, Canada

Bergonie Institute; 🇫🇷 Bordeaux, France

CHU of Quebec - Laval University; 🇨🇦 Quebec, Canada

Leon Berard Center; 🇫🇷 Lyon, France

Tenon Hospital; 🇫🇷 Paris, France

UMC Utrecht; 🇳🇱 Utrecht, Netherlands

Royal Surrey County Hospital; 🇬🇧 Guildford, United Kingdom

University Hospital Southampton NHS Foundation Trust; 🇬🇧 Southampton, United Kingdom

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

VA Ann Arbor Healthcare System; 🇺🇸 Ann Arbor, Michigan, United States

H. Lee Moffitt Cancer Center & Research Institute; 🇺🇸 Tampa, Florida, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

University of Michigan Hospitals; 🇺🇸 Ann Arbor, Michigan, United States

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Tulane Medical Center, Tulane Cancer Center; 🇺🇸 New Orleans, Louisiana, United States

Guy's Hospital; 🇬🇧 London, United Kingdom