Standard of Care +/- 177Lu-PSMA-617 In de Novo mHSPC Patients With Poor PSA Response (PEACE6-Poor Responders)

NCT06496581 | Recruiting Phase 3 DMC

• 2 other identifiers: UC-GTG-2301 (GETUG-AFU 42)2022-502408-57-00
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 25

Brief Summary

PEACE-6 Poor Responders is an international, multicenter, open-label, controlled, randomized, phase III trial to evaluate the efficacy and safety of 177Lu-PSMA-617 when administered on top of the ongoing standard systemic treatment compared to standard systemic treatment alone in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC) who do not present with a satisfactory response characterized by a serum prostatic specific antigen (PSA) level of ≥ 0.2 ng/mL at 6 to 8 months after systemic treatment initiation for mHSPC (i.e. poor responders) in the absence of evidence of cancer progression (including a rising PSA level).

Conditions

Prostate Cancer Metastatic

Keywords

Genital Diseases, Male; Prostatic Diseases; Hormones; 177Lu-PSMA-617; PSA

Outcome Measures

Primary Outcomes (2)

• Overall survival (OS)

  Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause.

  From randomization to death due to any cause, up to 8.5 years

• Radiographic progression-free survival (rPFS)

  Radiographic progression-free survival (rPFS) is defined as the time from randomization to the date of radiographic progression according to PCWG3 criteria by investigator assessment, or death, whichever occurs first.

  From randomization to radiographic progression or death, up to 8.5 years

Secondary Outcomes (9)

• Castration-Resistance Prostate Cancer-Free Survival (CRPC-FS)

  From randomization to onset of castration-resistance or death, up to 8.5 years

• Prostate Cancer-Specific Survival (PCSS)

  From the date of randomization to a PCSS event, up to 8.5 years

• PSA response

  From baseline over the treatment period, up to 8.5 years

• Skeletal-related event-free survival (SRE-FS)

  From randomization to the onset of a SRE-FS event, up to 8.5 years

• Time to severe urinary event (SUE)

  From randomization to the onset of a SUE event, up to 8.5 years

Study Arms (2)

Arm A (Control arm): Standard of Care (SoC) alone

ACTIVE COMPARATOR

The SoC is defined as one the following treatment which was initiated 6 to 8 months ahead of inclusion in this trial and still ongoing at the time of the randomization and continued at least until the CRPC stage is reached.: * ADT with an ARSI (i.e. abiraterone + prednisone, or apalutamide, or enzalutamide) ± radiotherapyª * ADT with docetaxelᵇ plus an ARSI (i.e. abiraterone + prednisone, or darolutamide,) ± radiotherapyª ª Radiotherapy can be part of any standard treatment aforementioned as long as it is not PSMA-based and completed at least 4 weeks ahead of randomization OR planned right after randomization in arm A. ᵇ Whenever docetaxel was part of the systemic treatment initiation, its administration must have been completed at least 4 weeks ahead of randomization.

Drug: Standard of Care

Arm B (Experimental arm): 177Lu-PMSA-617 + SoC

EXPERIMENTAL

Once every 6 weeks, 7400 MBq 177Lu-PMSA-617 will be administered for up to a total of 4 cycles. Upon 177Lu-PMSA-617 treatment completion, the ongoing standard systemic treatment is to be maintained and continued at least until the CRPC stage is reached. The SoC is defined as one the following treatment which was initiated 6 to 8 months ahead of inclusion in this trial and still ongoing at the time of the randomization: * ADT with an ARSI (i.e. abiraterone + prednisone, or apalutamide, or enzalutamide) ± radiotherapyª * ADT with docetaxelᵇ plus an ARSI (i.e. abiraterone + prednisone, or darolutamide,) ± radiotherapyª ª Radiotherapy can be part of any standard treatment aforementioned as long as it is not PSMA-based completed at least 4 weeks ahead of randomization OR planned right after 177Lu-PSMA-617 in arm B. ᵇ Whenever docetaxel was part of the systemic treatment initiation, its administration must have been completed at least 4 weeks ahead of randomization.

Drug: 177Lu-PMSA-617; Drug: Standard of Care

Interventions

177Lu-PMSA-617 DRUG

Once every 6 weeks, 7400 MBq 177Lu-PMSA-617 will be administered for up to a total of 4 cycles.

Also known as: Pluvicto®

Arm B (Experimental arm): 177Lu-PMSA-617 + SoC

Standard of Care DRUG

ADT, abiraterone and each ARSI (Apalutamide, Darolutamide, Enzalutamide) will be administrated according to the standard of care

Also known as: ADT with an ARSI (i.e. abiraterone + prednisone, or apalutamide, or enzalutamide) ± radiotherapy* or ADT with docetaxel* plus an ARSI (i.e abiraterone + prednisone, or darolutamide,) ± radiotherapy

Arm A (Control arm): Standard of Care (SoC) alone; Arm B (Experimental arm): 177Lu-PMSA-617 + SoC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All of the following criteria must be met ahead of randomization to satisfy trial eligibility requirements:
• Signed a written informed consent form prior to any trial specific procedures.
• Note: In case of physical incapacitation, a trusted representative of their choice, which is not the Investigator or sponsor, can sign on the behalf of the patients.
• Aged ≥18 years old
• Life expectancy \> 6 months as per investigator estimate
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Men with histologically or cytologically confirmed adenocarcinoma of the prostate
• De novo metastatic disease defined by clinical or radiographic evidence of metastases at diagnosis (i.e. before any treatment started). If not available, a more recent imaging can be used
• Measurable disease or bone lesions evaluable according to PCWG3 criteria. Patients with doubtful bone metastases are not eligible
• A pre-randomization 68Ga-PSMA-11 PET/CT scan performed within 4 weeks prior to randomization in the trial.
• FDG PET scan is not required for this protocol. All patients will be treated independently from the results of pre-randomization PSMA PET scan: patients with PSMA-positive or PSMA-negative disease according to PROMISE 2.0 criteria are eligible.
• Have 6 to 8 months of previous AND ongoing standard systemic treatment for prostate cancer consisting in either:
• ADT with an androgen receptor signaling inhibitor (ARSI) (i.e., abiraterone (plus prednisone), or apalutamide or enzalutamide) ± radiotherapy \*\*
• ADT with docetaxel\* plus an ARSI (i.e. abiraterone (plus prednisone), or darolutamide,) ± radiotherapy\*\*
• Note:

You may not qualify if:

• Patients presenting with any of the following criteria are not eligible:
• Any evidence of cancer progression (including a rising PSA level, clinical progression, or radiological progression)
• Prior or concurrent PSMA-based radioligand therapy or other PSMA target treatments
• Known hypersensitivity to the components of the study therapy or its analogs
• Any condition preventing the use of the standard of care and/or specific experimental treatments tested in the trial
• Any of the following within 6 months before randomization: stroke, myocardial infraction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure New York Heart Association (NYHA) Class III or IV
• Hypertension not controlled by an anti-hypertensive treatment (systolic blood pressure \[sBP\] ≥ 160 mmHg or diastolic blood pressure \[dBP\] ≥ 95 mmHg, 3 consecutive measures taken 5 minutes apart)
• Severe or uncontrolled concurrent disease, infection or co-morbidity
• Pathological findings consistent with small cell carcinoma of the prostate
• History of malignancy within 3 years of the current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma
• Ongoing participation in another clinical trial involving an investigational product.. Treatment with an investigational product must have ended within 28 days prior to the day of randomization
• Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
• Persons deprived of their liberty or under protective custody or guardianship

Sponsors & Collaborators

• UNICANCER: lead
• Novartis: collaborator

Study Sites (25)

Institut de Cancérologie de l'Ouest

Angers, France

NOT YET RECRUITING

Institut Bergonié

Bordeaux, France

NOT YET RECRUITING

CHRU Brest

Brest, France

NOT YET RECRUITING

Centre Francois Baclesse

Caen, France

NOT YET RECRUITING

CHU Henri Mondor

Créteil, France

NOT YET RECRUITING

Centre Georges-François Leclerc

Dijon, France

NOT YET RECRUITING

CHU Grenoble

Grenoble, France

NOT YET RECRUITING

Centre Léon Berard

Lyon, France

NOT YET RECRUITING

Institut Paoli-Calmettes

Marseille, France

RECRUITING

CHRU Nancy

Nancy, France

NOT YET RECRUITING

Centre Antoine Lacassagne

Nice, France

NOT YET RECRUITING

Hôpital Cochin

Paris, France

NOT YET RECRUITING

Hôpital Saint Louis

Paris, France

NOT YET RECRUITING

Institut Curie

Paris, France

NOT YET RECRUITING

Centre Eugène Marquis

Rennes, France

RECRUITING

Centre Henri Becquerel

Rouen, France

NOT YET RECRUITING

CHU Rouen

Rouen, France

NOT YET RECRUITING

Institut Curie

Saint-Cloud, France

NOT YET RECRUITING

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

NOT YET RECRUITING

CHU Saint Etienne

Saint-Priest-en-Jarez, France

NOT YET RECRUITING

ICANS

Strasbourg, France

NOT YET RECRUITING

IUCT Oncopole

Toulouse, France

NOT YET RECRUITING

CHRU Tours

Tours, France

NOT YET RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

NOT YET RECRUITING

Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Genital Diseases, Male; Prostatic Diseases

Interventions

Pluvicto; Standard of Care; Androgen Antagonists; Prednisone; apalutamide; enzalutamide; Radiotherapy; Docetaxel; darolutamide

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Karim FIZAZI, MD

  Gustave Roussy, Villejuif

  STUDY CHAIR

• Gwenaelle GRAVIS, MD

  IPC, Marseille

  STUDY CHAIR

Central Study Contacts

Florence TANTOT

CONTACT

+33 (1) 73.77.55.43; f-tantot@unicancer.fr

Catherine LEGER

CONTACT

+33 (7) 79.83.23.98; c-leger@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III, international, multicenter, randomized

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 11, 2024
• Study Start: September 12, 2024
• Primary Completion (Estimated): February 1, 2033
• Study Completion (Estimated): August 1, 2039
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: After primary analysis until end of trial
• Access Criteria: Steering committee approval

Locations

FR (25)