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

NCT06866938 | Recruiting Phase 2 DMC

• 2 other identifiers: 69HCL24_01832024-512043-22-00
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 16

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 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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Metastatic castration resistance prostate cancer; Internal vectorized radiotherapy; [177Lu]Lu-PSMA rechallenge

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival rate

  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.

  At 24 weeks after the start of study treatment

Secondary Outcomes (12)

• Imaging-based radiographic progression (rPFS)

  Through study completion, a maximum of 57 months

• Overall survival

  Through study completion, a maximum of 57 months

• Objective response rate

  Through study completion, a maximum of 57 months

• Duration of response

  Through study completion, a maximum of 57 months

• Disease Control Rate

  Through study completion, a maximum of 57 months

Study Arms (1)

[177Lu]Lu-PSMA-617

EXPERIMENTAL

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)

Drug: [177Lu]Lu-PSMA-617 (Pluvicto, Novartis)

Interventions

[177Lu]Lu-PSMA-617 (Pluvicto, Novartis) DRUG

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%)

[177Lu]Lu-PSMA-617

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 :

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (16)

Médecine Nucléaire, Institut Bergonié

Bordeaux, 33000, France

NOT YET RECRUITING

Oncologie Médicale, CHU Brest-Hôpital Morvan

Brest, 29200, France

NOT YET RECRUITING

Hôpital Louis Pradel, Hospices Civils de Lyon

Bron, 69500, France

NOT YET RECRUITING

Oncologie Médicale, Centre François Baclesse

Caen, 14076, France

NOT YET RECRUITING

Oncologie Médicale, Centre Jean Perrin

Clermont-Ferrand, 63011, France

NOT YET RECRUITING

Médecine Nucléaire, Centre Hospitalier de Grenoble Alpes

Grenoble, 38043, France

NOT YET RECRUITING

Médecine Nucléaire, Centre Léon Berard

Lyon, 69373, France

NOT YET RECRUITING

Médecine Nucléaire, CHU de Nantes Hôtel-Dieu

Nantes, 44000, France

NOT YET RECRUITING

Oncologie Médicale, Centre Antoine Lacassagne

Nice, 06189, France

NOT YET RECRUITING

Institut de cancérologie du Gard

Nîmes, 30000, France

NOT YET RECRUITING

Oncologie Médicale, Centre Hospitalier Lyon Sud, HCL

Pierre-Bénite, 69310, France

RECRUITING

Oncologie Médicale, Centre Henri Becqueret

Rouen, 76038, France

NOT YET RECRUITING

Oncologie Médicale, CHU Saint Etienne

Saint-Priest-en-Jarez, 42270, France

NOT YET RECRUITING

Médecine Nucléaire, Institut de Cancérologie de Strasbourg

Strasbourg, 67200, France

NOT YET RECRUITING

CHU de Nancy

Vandœuvre-lès-Nancy, 54511, France

NOT YET RECRUITING

Médecine Nucléaire, Institut Gustave Roussy

Villejuif, 94800, France

NOT YET RECRUITING

MeSH Terms

Interventions

Pluvicto; lactitol

Central Study Contacts

Denis MAILLET, Prof; MD/PhD

CONTACT

04 78 86 43 85; Denis.maillet@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective multicenter phase IIb single arm non randomized open-label study.

Study Record Dates

• First Submitted: February 26, 2025
• First Posted: March 10, 2025
• Study Start: April 11, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2030
• Last Updated: January 6, 2026

Record last verified: 2026-01

Locations

FR (16)