An Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Study Identifier:
CAAA617C12301
CT.gov Identifier:
NCT04720157
EudraCT Identifier:
2020-003968-56
EU Trial (CTIS) Number:
2023-507970-42-00
Study Contact Information:
N/A
Study Complete

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Study Summary

To evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with metastatic hormone-sensitive prostate cancer (mHSPC).

To assess the efficacy and safety of 177Lu-PSMA-617 plus SoC versus SoC alone in adults with metastatic hormone-sensitive prostate cancer (mHSPC).

To evaluate [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) combined with ADT + ARPI in PSMA+ mHSPC.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Prostate
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    III
    Sex
    Male
    Age
    18 - 100 Years
    Study Drug
  • Drug: Experimental: 177Lu-PSMA-617 Participant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA-617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); ARDT +ADT is considered as SOC and treatment will be administered per the physician's order Drug: 177Lu-PSMA-617 administered intravenously once every 6 weeks (1 cycle) for 6 cycles Drug: 68Ga-PSMA-11 Intravenous dose of approx. 150 Megabecquerel (MBq) at screening and at time of centrally confirmed rPD Drug: ARDT Administered orally on a continuous basis as per package insert and guideline Drug: ADT ADT are administered as per physician order Active Comparator: Standard of Care For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order Drug: 68Ga-PSMA-11 Intravenous dose of approx. 150 Megabecquerel (MBq) at screening and at time of centrally confirmed rPD Drug: ARDT Administered orally on a continuous basis as per package insert and guideline Drug: ADT ADT are administered as per physician order Patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq i.v. every 6 weeks, < or = 6 cycles) plus SOC or SOC alone (control arm). SOC is ARPI and androgen deprivation therapy ASCO 2023 Patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq every 6 weeks for a maximum of 6 cycles) plus SoC or SoC alone (an ARPI and ADT). Participants will receive intravenous 77Lu-PSMA-617 7.4 GBq (200 mCi) ± 10% once every 6 weeks (± 1 week) for up to six cycles plus SoC, or SoC alone (control). SoC includes a combination of ADT and an ARPI (e.g. abiraterone, apalutamide or enzalutamide). Treatment with SoC with or without 77Lu-PSMA-617 will continue until patients experience radiographic progression or until they are no longer clinically benefiting (at the treating physician's discretion). After treatment is discontinued, patients will enter the long-term follow-up period. Patients randomized to SoC will be allowed to cross over to receive 177Lu-PSMA-617 upon radiographic progression. Participants who have received 177Lu-PSMA-617 will have the option to enroll in a separate long-term safety follow-up study. Randomization was 1:1 to open-label 177Lu-PSMA-617 (7.4 GBq q6w, 6 cycles) + ADT + ARPI (177Lu-PSMA-617 arm) or ADT + ARPI (control arm), stratified by disease volume (high/low), age (≥/<70 years) and previous/planned primary tumor treatment (yes/no). Control arm patients with centrally confirmed rPD could cross over to 177Lu-PSMA-617 if eligible.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    Inclusion criteria
    • Participants eligible for inclusion in this study must meet all of the following criteria:
    • Signed informed consent must be obtained prior to participation in the study
    • Patients must be adults =18 years of age
    • Patients must have an ECOG performance status of 0 to 2
    • Patients must have a life expectancy >9 months as determined by the study investigator
    • Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
    • Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader
    • Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:
    • Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR
    • Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR
    • Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).
    • Patients must have adequate organ function:
    • Bone marrow reserve ANC =1.5 x 109/L Platelets =100 x 109/L Hemoglobin =9 g/dL
    • Hepatic Total bilirubin =2 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
    • Renal eGFR = 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
    • Albumin =2.5 g/dL
    • Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial
    • Patients must be:
    • Treatment naïve OR minimally treated with:
    • Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of study therapy or after 45 days whatever happens first.
    • If received, prior LHRH agonist/antagonist with or without first generation anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy.
    • Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.
    • Eligible patients are treatment-naive or minimally treated candidates for hormonal therapy, with PSMA-positive disease (determined by 68Ga-PSMA-11 PET/CT), ECOG performance status of 0 to 2 and adequate major organ function
    Exclusion criteria
    • Participants meeting any of the following criteria are not eligible for inclusion in this study.
    • Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
    • Any prior systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy (including monoclonal antibodies).
    • Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy
    • 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
    • Ongoing participation in any other clinical trial
    • Use of other investigational drugs within 30 days prior to day of randomization
    • Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
    • Transfusion for the sole purpose of making a participant eligible for study inclusion
    • Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed, baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).
    • Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
    • Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, 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. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance).
    • Active clinically significant cardiac disease defined as any of the following:
    • NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3.
    • History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
    • History of familial long QT syndrome or known family history of Torsades de Pointes
    • Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
    • History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
    • Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
    • Any condition that precludes raised arms position
    • Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.
    • Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
    • Eligible patients are treatment-naive or minimally treated candidates for hormonal therapy, with PSMA-positive disease (determined by 68Ga-PSMA-11 PET/CT), ECOG performance status of 0 to 2 and adequate major organ function

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Prostate