ReaLuP : Study on Re-treatment with Radiopharmaceutical Drug [177Lu]Lu-PSMA in Patients With Metastatic Castration-Resistant Prostate Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

11 Apr 2025 → ongoing

Decision date (initial)

2025-03-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ReaLuP received a financial support from Novartis.

External identifiers

EU CT number

2024-512043-22-00

ClinicalTrials.gov

NCT06866938

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To assess the efficacy of a re-treatment with [177Lu]Lu-PSMA-617 therapy on radiological progression free survival at 24 weeks in patients with mCRPC previously treated with ARSI and a first course of [177Lu]Lu-PSMA, without evidence of progression during this first course, and who progressed after at least 120 days after the end of the first course of [177Lu]Lu-PSMA

Secondary objectives 9

1. To evaluate the efficacy of a re-treatment with [177Lu]Lu-PSMA therapy on Radiological-based Progression Free Survival (rPFS) based on RECIST 1.1 or PCWG3 criteria
2. To evaluate the efficacy of a re-treatment with [177Lu]Lu-PSMA therapy on Overall Survival (OS), evaluated at short term (up to the end of active follow-up) and at long term (up to the end of the trial, i.e. two years after the end of the last active follow-up)
3. To evaluate the efficacy of a re-treatment with [177Lu]Lu-PSMA therapy on RECIST response as measured by RECIST v1.1 criteria to include : a) Overall Response Rate (ORR); b) Disease control rate (DCR); c) Duration of response (DOR)
4. To evaluate the efficacy of a re-treatment with [177Lu]Lu-PSMA therapy on Progression free survival (PFS) based on radiological/clinical/biological progression
5. To evaluate the efficacy of a re-treatment with [177Lu]Lu-PSMA therapy on Biochemical response as measured by PSA.
6. To evaluate the efficacy of a re-treatment with [177Lu]Lu-PSMA therapy on Time to PSA progression
7. To evaluate safety and tolerability of a re-treatment with [177Lu]Lu-PSMA-617
8. To assess quality of life of a re-treatment with [177Lu]Lu-PSMA-617 through evaluation of pain, SSE and QoL scores
9. Exploratory objective: To assess the efficacy on the following subgroups of patients on the primary outcome: patients with concordant results for baseline lesions detected on both 18F-FDG-PET/CT and [68Ga]-PSMA-PET/CT vs those with discordant results.

Conditions and MedDRA coding

Metastatic prostate cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Males ≥ 18 years of age
2. 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.
3. 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.
4. 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)
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 assessed within 7 days of study treatment initiation.
6. Histologically or cytologically confirmed adenocarcinoma of prostate. Patients with small cell carcinoma of the prostate may be included.
7. 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.
8. 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. 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; 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
9. 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.)
10. 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).
11. 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).
12. 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
13. Patients must have signed informed consent prior to participating in any study related procedures.
14. Willing and able to comply with the protocol, including follow-up visits and examinations.
15. Patients have to be affiliated to the French social security system or equivalent

Exclusion criteria 16

1. 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
2. More than one course of [177Lu]Lu-PSMA therapy
3. 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.
4. Any history of treatment with radium-223 dichloride or other systemic radiotherapy (including strontium-89, samarium-153, actinium-PSMA...)
5. Transfusion of red blood cells within 30 days prior to the first injection of the re-treatment of [177Lu]Lu-PSMA-617
6. Current central nervous system (CNS) metastases
7. Hypersensitivity to the active substance (Lutetium [177Lu] vipivotide tetraxetan or Gallium [68Ga] gozetotide) or to any of the excipients
8. Prior > hemibody external radiotherapy
9. Imminent or established spinal cord compression based on clinical findings and / or MRI that has not yet been treated
10. Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)
11. Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget’s disease of bone)
12. Ongoing participation in any other clinical trial who may interfere with the present study in the judgment of the investigator
13. 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.
14. Active clinically significant cardiac disease
15. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
16. Patients under tutorship or guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 15

1. 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.
2. 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
3. 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.
4. 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.
5. 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.
6. 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.
7. SAFETY : Percentage of patients with all grade and Serious AEs (SAEs)
8. SAFETY : Percentage of patients with Serious AEs (SAEs) during the active follow-up period
9. SAFETY : Percentage of patients with an interruption of [177Lu]Lu-PSMA-617 re-treatment
10. SAFETY : Percentage of patients who discontinue [177Lu]Lu-PSMA-617 re-treatment secondary to an AEs or death
11. SAFETY : Number and grade of AE related to the investigational medicinal product or to the procedures added by the research
12. QUALITY of LIFE: Pain assessed with the BPI-SF questionnaire.
13. 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.
14. QUALITY of LIFE : Aspects of HRQoL will be reported using Functional Assessment of Cancer Therapy – Prostate [FACT-P] questionnaire
15. Sub-group analyses : To assess radiological PFS at 24 weeks on the following subgroups of patients on the primary outcome: o Patients with concordant results at screening on both 18F-FDG-PET/CT and [68Ga]-PSMA-PET/CT vs o Patients with discordant results on those exams at screening: 18F-FDG-PET/CT positive lesions with no uptake on [68Ga]-PSMA-PET/CT.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Denis MAILLET

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Denis MAILLET

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications