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Re-treatment with a targeted radiotherapy for men with advanced prostate cancer

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

Phase 2 Interventional Hospices Civils de Lyon · NCT06866938

This study is testing if giving a targeted radiotherapy again can help men with advanced prostate cancer who previously responded to the treatment feel better and live longer.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment58 (estimated)
Ages18 Years and up
SexMale
SponsorHospices Civils de Lyon Academic / other
Drugs / interventionschemotherapy
Locations16 sites (Bordeaux and 15 other locations)
Trial IDNCT06866938 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of re-treating men with metastatic castration-resistant prostate cancer (mCRPC) using the radioligand [177Lu]Lu-PSMA-617 after they have previously responded to this treatment. Participants must have progressed after taxane-based therapy and show no evidence of progression during their initial treatment with [177Lu]Lu-PSMA-617. The treatment will continue until disease progression, unacceptable toxicity, or death, or for up to 9 months after the last dose. The study aims to improve patient outcomes by assessing the effectiveness of this re-treatment strategy.

Who should consider this trial

Good fit: Ideal candidates are men aged 18 and older with confirmed mCRPC who have previously responded to [177Lu]Lu-PSMA-617 and have progressed after taxane-based therapy.

Not a fit: Patients who have not previously responded to [177Lu]Lu-PSMA-617 or those with non-metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for men with mCRPC who have previously benefited from [177Lu]Lu-PSMA-617.

How similar studies have performed: Previous studies have shown success with [177Lu]Lu-PSMA-617 in treating mCRPC, indicating potential for this re-treatment approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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).
* 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

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

Where this trial is running

Bordeaux and 15 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Castration-resistant Prostate CancerMetastatic castration resistance prostate cancerInternal vectorized radiotherapy[177Lu]Lu-PSMA rechallenge
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.