LUTETIUM (177LU) VIPIVOTIDE TETRAXETAN for Metastatic castration-resistant prostate cancer (mCRPC)|Metastatic prostate cancer

Inclusion criteria

• {"criterion_text":"- Males ≥ 18 years of age\n- Participants must have been previously treated with at least 4 consecutive cycles of [177Lu]Lu-PSMA with no evidence of progression during this first course of treatment (including radiological, clinical but also PSA progression).\n- Participants must have been previously treated with at least one ARSI - Androgen Receptor Signaling Inhibitors - (including enzalutamide, apalutamide, abiraterone or darolutamide) initiated for mCSPC, nmCRPC or mCRPC. (ARSI may be also administered together with [177Lu]Lu-PSMA-617 provided that the patient has not received an identical ARSI in the past and that this ARSI was initiated at least 15 days before the first cycle of [177Lu]Lu-PSMA-617 and less than 2 months ago. The ARSI administrated in association with LuPSMA should not be considered as a prior therapy. A previous ARSI treatment is mandatory for patient eligibility).\n- Patients must have been previously treated with at least one taxane based chemotherapy (with docetaxel or cabazitaxel) The number of previously administrated lines of taxane-based therapy is not limited ; patients can have received a taxane-based chemotherapy before or after the first sequence of [177Lu]Lu-PSMA\n- Patients must have signed informed consent prior to participating in any study related procedures.\n- Willing and able to comply with the protocol, including follow-up visits and examinations.\n- Patients have to be affiliated to the French social security system or equivalent\n- Patients must have progressed at least 120 days after the last injection of the first course of [177Lu]Lu-PSMA therapy. Patients with a radiological or clinical progressive disease during the first 120 days after the last cycle of the first course of [177Lu]Lu-PSMA are not eligible. PSA progression is defined by a ≥ 25% increase in PSA and an absolute increase of 2 ng/mL or more from the NADIR and confirmed by a second consecutive value obtained 3 or more weeks later. Patients treated with chemotherapy, ARSI or PARP inhibitors, between the first 117LuPSMA course and screening are also eligible.\n- Be abstinent from heterosexual intercourse OR must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary medical cause) until 98 days (14 weeks) post-treatment.\n- Adequate organ functions : a.Bone marrow reserve (i.ANC ≥1.5 X 10^9/L; ii.Platelets ≥100 X 10^9/L; iii.Hemoglobin ≥10 g/dL); b. Hepatic (i.Total bilirubin ≤2 x ULN. For patients with known Gilbert’s syndrome ≤3 x ULN.; ii.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 x ULN); c. Renal (Clearance ≥40 ml/mn)\n- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 assessed within 7 days of study treatment initiation.\n- Histologically or cytologically confirmed adenocarcinoma of prostate. Patients with small cell carcinoma of the prostate may be included.\n- Metastatic disease documented by at least one lesion on bone scan or abdominal/pelvic/chest computed tomography (CT) or magnetic resonance imaging (MRI) scan assessed by investigator. Patients without bone metastasis must have measurable lesions in extra-pelvic lymph nodes or in soft-tissues as defined by RECIST 1.1 criteria.\n- Confirmed progression mCRPC despite ongoing androgen deprivation with serum testosterone < 50ng/dl (1.7nM) within 3 months prior to screening. Progression is defined by the presence of at least one of the following criteria : a.\tPSA progression using local laboratory values as defined by a minimum of 2 consecutive rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥1 ng/mL; b. Radiographic disease progression in bone based on PCWG3 criteria defined as the appearance of 2 or more new bone lesions on bone scan, with or without PSA progression.; c. Radiographic disease progression in extra-pelvic lymph nodes based or soft-tissues on RECIST1.1 criteria with or without PSA progression\n- PSMA positive metastatic lesions on [68Ga]-PSMA-PET/CT without PSMA negative lesion. (The presence of PSMA-positive lesions is defined as [68Ga]-PSMA-11 uptake greater than that of liver parenchyma in one or more metastatic lesions of any size in any organ system. The presence of PSMA-negative lesions is defined as PSMA uptake equal to or lower than that of liver parenchyma in any lymph node with a short axis of at least 2.5 cm, in any metastatic solid-organ lesions with a short axis of at least 1.0 cm, or in any metastatic bone lesion with a soft-tissue component of at least 1.0 cm in the short axis. Patients with any PSMA negative metastatic lesion meeting these criteria are ineligible.)"}

Exclusion criteria

• {"criterion_text":"- History of a [177Lu]Lu-PSMA serious adverse event (SAE) or CTCAE Grade 3 or 4 AE during the initial course of [177Lu]Lu-PSMA that led to the discontinuation of treatment\n- Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)\n- Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget’s disease of bone)\n- Ongoing participation in any other clinical trial who may interfere with the present study in the judgment of the investigator\n- Concurrent serious (as determined byl 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.\n- Active clinically significant cardiac disease\n- History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study\n- Patients under tutorship or guardianship\n- More than one course of [177Lu]Lu-PSMA therapy\n- Less than 120 days from the last dose administrated in the initial course of [177Lu]Lu-PSMA treatment and the clinical or radiological disease progression, or the initiation of a subsequent therapy.\n- Any history of treatment with radium-223 dichloride or other systemic radiotherapy (including strontium-89, samarium-153, actinium-PSMA...)\n- Transfusion of red blood cells within 30 days prior to the first injection of the re-treatment of [177Lu]Lu-PSMA-617\n- Current central nervous system (CNS) metastases\n- Hypersensitivity to the active substance (Lutetium [177Lu] vipivotide tetraxetan or Gallium [68Ga] gozetotide) or to any of the excipients\n- Prior > hemibody external radiotherapy\n- Imminent or established spinal cord compression based on clinical findings and / or MRI that has not yet been treated"}

Primary endpoints

• {"endpoint_text":"- Percentage of patients with radiological progression free survival (based on RECIST 1.1 or PCWG3 criteria) at 24 weeks from the first day of study treatment administration, assessed with imaging (bone scan and CT-scan).","definition_or_measurement_approach":"Assessed with imaging (bone scan and CT-scan) using RECIST 1.1 or PCWG3 criteria at 24 weeks from the first day of study treatment administration."}

Secondary endpoints

• {"endpoint_text":"- EFFICACY : Imaging base radiographic progression (rPFS) defined as the time from the first cycle of [177Lu]Lu-PSMA-617 re-treatment to the date of radiographic disease progression as outlined in Prostate Cancer Working Group 3 (PCWG3) Guidelines or death from any cause.","definition_or_measurement_approach":"Time from first cycle of re-treatment to radiographic disease progression per PCWG3 guidelines or death from any cause."}
• {"endpoint_text":"- EFFICACY: Overall survival defined as the time from the first cycle of [177Lu]Lu-PSMA-617 re-treatment to the date of death from any cause","definition_or_measurement_approach":"Time from first cycle of re-treatment to date of death from any cause."}
• {"endpoint_text":"- EFFICACY : RECIST response including: i.Objective response rate (ORR) (CR + PR) as measured by RECIST v1.1 response in soft tissue, lymph node and visceral lesions. Duration of Response (DOR) will also be measured in patients with a CR or PR from date of first response to the date of RECIST progression or death. ii.Disease Control Rate (DCR) (CR + PR + stable disease [SD]) as measured by RECIST v1.1 response in soft tissue, lymph node and visceral lesions.","definition_or_measurement_approach":"RECIST v1.1 measurements in soft tissue, lymph node and visceral lesions to determine ORR (CR+PR), DCR (CR+PR+SD) and DOR (from first response to RECIST progression or death)."}
• {"endpoint_text":"- EFFICACY : Progression-free survival defined as the date of first cycle of [177Lu]Lu-PSMA-617 re-treatment to the date of first evidence of radiographic progression, clinical progression, PSA progression, or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Time from first cycle of re-treatment to first evidence of radiographic, clinical, or PSA progression, or death."}
• {"endpoint_text":"- EFFICACY : Biological response endpoints: Proportion of participants with a PSA response defined as a patient who has achieved a ≥ 50% PSA decrease from baseline that is confirmed with a second PSA measurement at ≥ 4 weeks.","definition_or_measurement_approach":"Proportion with ≥50% PSA decrease from baseline confirmed by a second PSA measurement at ≥4 weeks."}
• {"endpoint_text":"- EFFICACY : Time to PSA progression defined as the date from first cycle of [177Lu]Lu-PSMA-617 re-treatment to a ≥25% increase in PSA and an absolute increase of 2ng/mL or more from the nadir and confirmed by a second consecutive value obtained 3 or more weeks later.","definition_or_measurement_approach":"Time from first cycle to ≥25% and ≥2 ng/mL absolute increase in PSA from nadir, confirmed by a second consecutive value ≥3 weeks later."}
• {"endpoint_text":"- SAFETY : Percentage of patients with all grade and Serious AEs (SAEs)","definition_or_measurement_approach":"Proportion of patients experiencing adverse events of any grade and serious adverse events during study periods."}
• {"endpoint_text":"- SAFETY : Percentage of patients with Serious AEs (SAEs) during the active follow-up period","definition_or_measurement_approach":"Proportion of patients experiencing SAEs during the active follow-up period."}
• {"endpoint_text":"- SAFETY : Percentage of patients with an interruption of [177Lu]Lu-PSMA-617 re-treatment","definition_or_measurement_approach":"Proportion of patients who have an interruption of re-treatment with [177Lu]Lu-PSMA-617."}
• {"endpoint_text":"- SAFETY : Percentage of patients who discontinue [177Lu]Lu-PSMA-617 re-treatment secondary to an AEs or death","definition_or_measurement_approach":"Proportion of patients who permanently discontinue re-treatment due to adverse events or death."}
• {"endpoint_text":"- SAFETY : Number and grade of AE related to the investigational medicinal product or to the procedures added by the research","definition_or_measurement_approach":"Count and CTCAE grade of adverse events related to the investigational medicinal product or study-specific procedures."}
• {"endpoint_text":"- QUALITY of LIFE: Pain assessed with the BPI-SF questionnaire.","definition_or_measurement_approach":"Pain assessment using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire."}
• {"endpoint_text":"- QUALITY of LIFE : Time to first symptomatic skeletal event (SSE) and SSE-free survival defined as date of first injection of [177Lu]Lu-PSMA-617 re-treatment to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, or requirement for radiation therapy to relieve bone pain, whichever occurs first.","definition_or_measurement_approach":"Time from first injection to first symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgery, or need for radiation to relieve bone pain; SSE-free survival measured similarly."}
• {"endpoint_text":"- QUALITY of LIFE : Aspects of HRQoL will be reported using Functional Assessment of Cancer Therapy – Prostate [FACT-P] questionnaire","definition_or_measurement_approach":"Health-related quality of life measured with the FACT-P questionnaire at baseline and 24 weeks after treatment start."}
• {"endpoint_text":"- Sub-group analyses : To assess radiological PFS at 24 weeks on the following subgroups of patients on the primary outcome: o\tPatients with concordant results at screening on both 18F-FDG-PET/CT and [68Ga]-PSMA-PET/CT vs o\tPatients with discordant results on those exams at screening: 18F-FDG-PET/CT positive lesions with no uptake on [68Ga]-PSMA-PET/CT.","definition_or_measurement_approach":"Subgroup rPFS at 24 weeks comparing patients with concordant vs discordant 18F-FDG-PET/CT and [68Ga]-PSMA-PET/CT results at screening."}

France

Earliest CTIS Part Ii Submission Date

07-02-2025

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

369

Number Of Sites

16

Number Of Participants

58

Primary sponsor

Full Name

Hospices Civils De Lyon

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France