Study of Re-treatment With [177Lu]Lu-PSMA in Men With Metastatic Castration Resistance Prostate Cancer

Официальное название

An Open Label, Single Arm Phase IIb Study of Re-treatment With [177Lu]Lu-PSMA in Men With Metastatic Castration Resistance Prostate Cancer

Обзор

Prostate cancer is the third leading cause of cancer-related death in men in the United States and Europe. The treatment of metastatic castration-resistant prostate cancer (mCRPC) has evolved with the arrival of the radioligand \[177Lu\]Lu-PSMA-617, which specifically targets PSMA-expressing cancer cells. The randomized phase III VISION study showed that \[177Lu\]Lu-PSMA-617 significantly improved progression-free survival and overall survival with an acceptable toxicity profile. The ReaLuP study will evaluate the efficacy of a re-treatment of \[177Lu\]Lu-PSMA-617 in patients with progressive PSMA-positive mCRPC and who have been previously treated with \[177Lu\]Lu-PSMA without evidence of progression during this first course of treatment. Patients will be treated until disease progression, unacceptable toxicity or death, or alternatively up to 9 months after the last dose of treatment. At the end of this follow up period, patients will enter the " long term follow up ", at least for 2 years after the end of the last active follow-up.

Вмешательства

• Препарат [177Lu]Lu-PSMA-617 (Pluvicto, Novartis)
  Patients will be treated with intravenous \[177Lu\]Lu-PSMA-617 (Pluvicto, Novartis). One injection every 6 weeks at the dose of 7.4 GBq (±10%)

Первичные конечные точки

• Progression-Free Survival rate [Срок оценки: At 24 weeks after the start of study treatment]

Вторичные конечные точки (12)

• Imaging-based radiographic progression (rPFS) [Срок оценки: Through study completion, a maximum of 57 months]
• Overall survival [Срок оценки: Through study completion, a maximum of 57 months]
• Objective response rate [Срок оценки: Through study completion, a maximum of 57 months]
• Duration of response [Срок оценки: Through study completion, a maximum of 57 months]
• Disease Control Rate [Срок оценки: Through study completion, a maximum of 57 months]
• Progression free survival [Срок оценки: Through study completion, a maximum of 57 months]
• Biological response [Срок оценки: Through study completion, a maximum of 57 months]
• Time to PSA progression [Срок оценки: Through study completion, a maximum of 57 months]
• Safety : Adverse Events [Срок оценки: Through study completion, a maximum of 57 months]
• Pain assessment [Срок оценки: Up to 6 weeks from the last [177Lu]Lu-PSMA-617 administration]
• Quality of life assessment [Срок оценки: Up to 6 weeks from the last [177Lu]Lu-PSMA-617 administration]
• Symptomatic Skeletal Event (SSE) assessment [Срок оценки: Through study completion, a maximum of 57 months]

Критерии участия

Критерии включения

• Males ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 assessed within 7 days of study treatment initiation
• Histologically or cytologically confirmed adenocarcinoma of prostate (Patients with small cell carcinoma of the prostate may be included)
• 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
• 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 :

• PSA 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
• 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
• Radiographic disease progression in extra-pelvic lymph nodes based or soft-tissues on RECIST1.1 criteria with or without PSA progression
• 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).
• 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).
• 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)
• 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)
• Patients must have been 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).
• 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.
• Adequate organ functions :

• Bone marrow reserve :

• ANC ≥ 1.5 X 109/L
• Platelets ≥ 100 X 109/L
• Hemoglobin ≥ 10 g/dL
• Hepatic :

• Total bilirubin ≤ 2 x ULN. For patients with known Gilbert's syndrome ≤ 3 x ULN.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 x ULN
• Renal :

• Clearance ≥40 ml/mn
• Patients must have signed informed consent prior to participating in any study related procedures
• Willing and able to comply with the protocol, including follow-up visits and examinations
• Patients have to be affiliated to the French social security system, or equivalent

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 16 центров

• Médecine Nucléaire, Institut Bergonié — Bordeaux
• Oncologie Médicale, CHU Brest-Hôpital Morvan — Brest
• Hôpital Louis Pradel, Hospices Civils de Lyon — Bron
• Oncologie Médicale, Centre François Baclesse — Caen
• Oncologie Médicale, Centre Jean Perrin — Clermont-Ferrand
• Médecine Nucléaire, Centre Hospitalier de Grenoble Alpes — Grenoble
• Médecine Nucléaire, Centre Léon Berard — Lyon
• Médecine Nucléaire, CHU de Nantes Hôtel-Dieu — Nantes
• … и ещё 8 центров

Идентификаторы

NCT: NCT06866938 · 69HCL24_0183 · 2024-512043-22-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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