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

Phase 2

Not yet recruiting

• Conditions: Metastatic Castration-resistant Prostate Cancer
• Interventions: Drug: [177Lu]Lu-PSMA-617 (Pluvicto, Novartis)

• Registration Number: NCT06866938
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

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 mCRPC patients progressing after taxane based therapy 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-26
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-04
• Last Update Submitted: 2025-03-04
• Study First Posted: 2025-03-10
• Last Update Posted: 2025-03-10
• Study Start: 2025-04
• Primary Completion: 2027-04
• Study Completion: 2030-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 58

Inclusion Criteria

• 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). (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)

• 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)

• Patients must have been treated with at least one course of taxane based chemotherapy (docetaxel or cabazitaxel) after the first course of [177Lu]Lu-PSMA therapy. (Patients treated with PARP inhibitors, or more than one course of chemotherapy 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[177Lu]Lu-PSMA-617	[177Lu]Lu-PSMA-617 (Pluvicto, Novartis)	Patients with metastatic castration resistance prostate cancer will be treated with intravenous \[177Lu\]Lu-PSMA-617 (Pluvicto, Novartis) at the dose of 7.4 GBq (±10%) every 6 weeks Treatment duration: 4 to 6 cycles (24 to 36 weeks)

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival rate	At 24 weeks after the start of study treatment	Proportion (in %) of patients alive without disease progression at 24 weeks. Progression is defined by imaging (bone scan and CT-scan) according to RECIST 1.1 and/or PCWG3 criteria.

Secondary Outcome Measures

Name	Time	Method
Imaging-based radiographic progression (rPFS)	Through study completion, a maximum of 57 months	Imaging-based radiographic progression defined as the time from the first cycle of re-treatment to the date of radiographic disease progression or death from any cause.
Overall survival	Through study completion, a maximum of 57 months	Overall Survival (Os) defined as the time from the first cycle of re-treatment to the date of death from any cause
Objective response rate	Through study completion, a maximum of 57 months	Objective response rate (ORR) (Complete Response (CR) + Partial Response (PR)) measured by RECIST v1.1 response.
Duration of response	Through study completion, a maximum of 57 months	Duration of response (DOR) will be measured in patients who achieved a CR or PR between the date of first response and the date of RECIST progression or death.
Disease Control Rate	Through study completion, a maximum of 57 months	Disease control rate as measured by RECIST v1.1 response. Rates will be measured in soft tissue, lymph nodes and visceral lesions.
Progression free survival	Through study completion, a maximum of 57 months	Progression free survival will be 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.
Biological response	Through study completion, a maximum of 57 months	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.
Time to PSA progression	Through study completion, a maximum of 57 months	Time to PSA progression will be 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 2 ng/mL or more from the nadir and confirmed by a second consecutive value obtained 3 or more weeks later. Where no decline from baseline is documented, PSA progression is 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 of treatment.
Safety : Adverse Events	Through study completion, a maximum of 57 months	Safety of re-treatment will be assessed by percentage of patients with all grade and Serious AEs; percentage of patients with SAEs during the active follow up period; percentage of patients with an interruption of \[177Lu\]Lu-PSMA-617 re-treatment; Percentage of patients who discontinue \[177Lu\]Lu-PSMA-617 re-treatment secondary to an AEs or death; Number and grade of AE related to the investigational medicinal product or to the procedures added by the research
Pain assessment	Up to 6 weeks from the last [177Lu]Lu-PSMA-617 administration	Pain will be assessed with the BPI-SF (Brief Pain Inventory - Short Form) questionnaire
Quality of life assessment	Up to 6 weeks from the last [177Lu]Lu-PSMA-617 administration	Aspects of HRQoL will be reported using Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire
Symptomatic Skeletal Event (SSE) assessment	Through study completion, a maximum of 57 months	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.

Trial Locations

Locations (13)

Oncologie Médicale, Centre Antoine Lacassagne; 🇫🇷 Nice, France

Oncologie Médicale, Centre Hospitalier Lyon Sud, HCL; 🇫🇷 Pierre-Bénite, France

Oncologie Médicale, Centre Henri Becqueret; 🇫🇷 Rouen, France

Oncologie Médicale, CHU Saint Etienne; 🇫🇷 Saint-Priest-en-Jarez, France

Médecine Nucléaire, Institut de Cancérologie de Strasbourg; 🇫🇷 Strasbourg, France

Médecine Nucléaire, Institut Gustave Roussy; 🇫🇷 Villejuif, France

Médecine Nucléaire, Institut Bergonié; 🇫🇷 Bordeaux, France

Oncologie Médicale, CHU Brest-Hôpital Morvan; 🇫🇷 Brest, France

Oncologie Médicale, Centre François Baclesse; 🇫🇷 Caen, France

Oncologie Médicale, Centre Jean Perrin; 🇫🇷 Clermont-Ferrand, France

Médecine Nucléaire, Centre Hospitalier de Grenoble Alpes; 🇫🇷 Grenoble, France

Médecine Nucléaire, Centre Léon Berard; 🇫🇷 Lyon, France

Médecine Nucléaire, CHU de Nantes Hôtel-Dieu; 🇫🇷 Nantes, France