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

A Randomized Phase III Trial Evaluating the Efficacy and Safety of Standard of Care +/- 177Lu-PSMA617 in de Novo Metastatic Hormone-sensitive Prostate Cancer Patients Having a PSA≥0.2 ng/mL at 6-8 Months After Systemic Treatment Initiation

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).

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Drug: Standard of Care; Drug: 177Lu-PMSA-617

Detailed Description

The study plans to enroll 500 patients over 63 months who will be randomized (1:1) to receive either: (i) Control arm: SoC (ADT+ ARSI (second-generation androgen receptor signaling inhibitors) +/- RT or ADT+ ARSI +/- RT) or (ii) Experimental arm: 177Lu-PSMA-617 + SoC (ADT+ ARSI +/- RT or ADT+ docetaxel + ARSI +/- RT). Response to treatment will be assessed according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Treatment will be continued at least until castration-resistant prostate cancer (CRPC) stage is reached, defined by evidence of cancer progression (either a confirmed PSA rise or a radiographic progression) with serum testosterone being at castrated levels (<0.50 ng/mL). This systemic treatment may be continued after CRPC is reached, based on patient benefit and the investigator's opinion. Treatment may also be terminated at the initiative of either the patient or the investigator for any reason that would be beneficial to the patient, including: unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient request. At the end of treatment period, the follow-up period will last for 102 months (8.5 years). The overall trial duration, including the follow-up, is expected to last 18.5 years.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Florence TANTOT; Phone Number: +33 (1) 73.77.55.43; Email: f-tantot@unicancer.fr
• Study Contact Backup: Name: Catherine LEGER; Phone Number: +33 (7) 79.83.23.98; Email: c-leger@unicancer.fr

Study Locations

• France
  • Angers, France
    • Not yet recruiting
    • Institut de Cancérologie de l'Ouest
    • Principal Investigator: Elouen BOUGHALEM, MD
    • Contact: Elouen BOUGHALEM, MD
  • Bordeaux, France
    • Not yet recruiting
    • Institut Bergonie
    • Contact: Paul Schwartz, MD
    • Principal Investigator: Paul SCHWARTZ, MD
  • Brest, France
    • Not yet recruiting
    • CHRU BREST
    • Principal Investigator: Friederike Schlurmann, MD
    • Contact: Friederike Schlurmann, MD
  • Caen, France
    • Not yet recruiting
    • Centre Francois Baclesse
    • Contact: Florence Joly, MD
    • Principal Investigator: Florence Joly, MD
  • Créteil, France
    • Not yet recruiting
    • CHU Henri Mondor
    • Contact: Caroline Saldana, MD
    • Principal Investigator: Caroline Saldana, MD
  • Dijon, France
    • Not yet recruiting
    • Centre Georges-François Leclerc
    • Contact: Clément Drouet, MD
    • Principal Investigator: Clément Drouet, MD
  • Grenoble, France
    • Not yet recruiting
    • CHU Grenoble
    • Principal Investigator: Loic Djaileb, MD
    • Contact: Loic Djaileb, MD
  • Lyon, France
    • Not yet recruiting
    • Centre Leon Berard
    • Principal Investigator: Aude FLECHON, MD
    • Contact: Aude FLECHON, MD
  • Marseille, France
    • Recruiting
    • Institut Paoli-Calmettes
    • Contact: Gwenaelle Gravis, MD
    • Principal Investigator: Gwenaelle GRAVIS, MD
  • Nancy, France
    • Not yet recruiting
    • CHRU Nancy
    • Contact: Pierre Olivier, MD
    • Principal Investigator: Pierre Olivier, MD
  • Nice, France
    • Not yet recruiting
    • Centre Antoine Lacassagne
    • Principal Investigator: Delphine BORCHIELLINI, MD
    • Contact: Delphine Borchiellini, MD
  • Paris, France
    • Not yet recruiting
    • Institut Curie
    • Contact: Zahra Castel-Ajgal, MD
    • Principal Investigator: Zahra Castel-Ajgal, MD
  • Paris, France
    • Not yet recruiting
    • Hopital Saint Louis
    • Contact: Hélène GAUTHIER
    • Principal Investigator: Hélène Gauthier, MD
  • Paris, France
    • Not yet recruiting
    • Hôpital Cochin
    • Contact: Olivier Hullard, MD
    • Principal Investigator: Olivier Hullard, MD
  • Rennes, France
    • Recruiting
    • Centre Eugene Marquis
    • Principal Investigator: Laurence CROUZET, MD
    • Contact: Laurence Crouzet, MD
  • Rouen, France
    • Not yet recruiting
    • Centre Henri Becquerel
    • Contact: David Tonnelet, MD
    • Principal Investigator: David Tonnelet, MD
  • Rouen, France
    • Not yet recruiting
    • Chu Rouen
    • Contact: Laetitia AUGUSTO, MD
    • Principal Investigator: Laetitia AUGUSTO, MD
  • Saint-Cloud, France
    • Not yet recruiting
    • Institut Curie
    • Contact: Capucine Richard, MD
    • Principal Investigator: Capucine Richard, MD
  • Saint-Herblain, France
    • Not yet recruiting
    • Institut de Cancérologie de l'Ouest
    • Contact: Emmanuelle BOMPAS, MD
    • Principal Investigator: Emmanuelle BOMPAS, MD
  • Saint-Priest-en-Jarez, France
    • Not yet recruiting
    • CHU Saint Etienne
    • Principal Investigator: Pierre CORNILLON, MD
    • Contact: Pierre CORNILLON, MD
  • Strasbourg, France
    • Not yet recruiting
    • ICANS
    • Principal Investigator: Philippe BARTHELEMY, MD
    • Contact: Philippe BARTHELEMY, MD
  • Toulouse, France
    • Not yet recruiting
    • IUCT Oncopole
    • Contact: Loïc MOUREY, MD
    • Principal Investigator: Loic Mourey, MD
  • Tours, France
    • Not yet recruiting
    • CHRU Tours
    • Principal Investigator: Mathilde CANCEL, MD
    • Contact: Mathilde CANCEL, MD
  • Vandœuvre-lès-Nancy, France
    • Not yet recruiting
    • Institut de Cancérologie de Lorraine
    • Contact: Vincent Massard, MD
    • Principal Investigator: Vincent MASSARD, MD
  • Villejuif, France
    • Recruiting
    • Gustave Roussy
    • Principal Investigator: Karim Fizazi, MD
    • Contact: Karim FIZAZI, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All of the following criteria must be met ahead of randomization to satisfy trial eligibility requirements:

1. 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.

2. Aged ≥18 years old
3. Life expectancy > 6 months as per investigator estimate
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
5. Men with histologically or cytologically confirmed adenocarcinoma of the prostate
6. 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
7. Measurable disease or bone lesions evaluable according to PCWG3 criteria. Patients with doubtful bone metastases are not eligible

8. 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.

9. 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:

   *Docetaxel must have been stopped at least 4 weeks ahead of randomization.

   ** Previous radiotherapy to the primary tumor and/or to the metastases is accepted as long as it was not PSMA-based and must has been completed at least 4 weeks ahead of randomization.

10. Stable or declining PSA level but not a rising one
11. Serum PSA of ≥ 0.2 ng/mL at 6 to 8 months after systemic treatment initiation
12. Testosterone level < 50 ng/dl or < 1.7 nmol/L

13. Be fit enough for 177Lu-vipivotide tetraxetan treatment:

    • Adequate bone marrow function: hemoglobin ≥90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomization), absolute neutrophil count ≥1.5 x10⁹/L, platelet count >100 x10⁹/L
    • Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.0 x upper limit of normal (ULN), or ≤ 5.0 x ULN in the presence of liver metastases; bilirubin <1.5 x ULN (unless known or suspected Gilbert syndrome, then <3 x ULN is permitted)
    • Adequate renal function: calculated creatinine clearance ≥ 50 ml/min (using the MDRD or CKD EPI method).
14. For sexually active men with female partners of reproductive potential or with pregnant women, agreement to use a condom with another effective contraceptive method during trial participation and up to 14 weeks after study treatment completion.
15. Affiliated to the social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials).
16. Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion Criteria:

Patients presenting with any of the following criteria are not eligible:

1. Any evidence of cancer progression (including a rising PSA level, clinical progression, or radiological progression)
2. Prior or concurrent PSMA-based radioligand therapy or other PSMA target treatments
3. Known hypersensitivity to the components of the study therapy or its analogs
4. Any condition preventing the use of the standard of care and/or specific experimental treatments tested in the trial
5. 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
6. 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)
7. Severe or uncontrolled concurrent disease, infection or co-morbidity
8. Pathological findings consistent with small cell carcinoma of the prostate
9. History of malignancy within 3 years of the current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma
10. 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
11. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
12. Persons deprived of their liberty or under protective custody or guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (Control arm): Standard of Care (SoC) alone; 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; ADT, abiraterone and each ARSI (Apalutamide, Darolutamide, Enzalutamide) will be administrated according to the standard of care; Other Names: 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
Experimental: Arm B (Experimental arm): 177Lu-PMSA-617 + SoC; 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: Standard of Care; ADT, abiraterone and each ARSI (Apalutamide, Darolutamide, Enzalutamide) will be administrated according to the standard of care; Other Names: 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; Drug: 177Lu-PMSA-617; Once every 6 weeks, 7400 MBq 177Lu-PMSA-617 will be administered for up to a total of 4 cycles.; Other Names: Pluvicto®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Castration-Resistance Prostate Cancer-Free Survival (CRPC-FS)	Castration-Resistance Prostate Cancer-Free Survival (CRPC-FS) is defined as the time from randomization to the onset of castration-resistance or death from any cause, whichever occurs first.	From randomization to onset of castration-resistance or death, up to 8.5 years
Prostate Cancer-Specific Survival (PCSS)	Prostate Cancer-Specific Survival (PCSS) is defined as the time from the date of randomization to the date of death due to prostate cancer.	From the date of randomization to a PCSS event, up to 8.5 years
PSA response	PSA response will be assessed by the maximum change of PSA (rise or fall) from baseline over the treatment period. A complete PSA response is defined by an undetectable level of serum PSA.	From baseline over the treatment period, up to 8.5 years
Skeletal-related event-free survival (SRE-FS)	Skeletal-related event-free survival (SRE-FS) is defined as the time from the randomization date to the date of diagnosis of either a skeletal-related event (SRE) (fracture, or bone pain requiring radiation therapy, or spinal cord compression, or preventive surgery to the bones) or death, whichever occurs first.	From randomization to the onset of a SRE-FS event, up to 8.5 years
Time to severe urinary event (SUE)	Time to severe urinary event (SUE) is defined as the time from the randomization date to the date of diagnosis of either one of the following SUE, whichever occurs first: urinary retention with need for a urinary catheter, suprapubic catheter, double J stent, nephrostomy, treatment of the prostate by radiotherapy or trans-urethral resection of the prostate (TURP) or prostatectomy done to relieve patients with local symptoms.	From randomization to the onset of a SUE event, up to 8.5 years
Time to initiation of first subsequent anti-cancer systemic therapy for CRPC (TTSST1)	TTSST1 is defined as the time from the randomization date to the date of initiation of the first anti-cancer systemic therapy for CRPC.	From randomization to initiation of the first anti-cancer systemic therapy for CRPC, up to 10 years
Time to initiation of second subsequent anti-cancer systemic therapy for CRPC (TTSST2)	TTSST2 is defined as the time from the randomization date to the date of initiation of the second anti-cancer systemic therapy for CRPC.	From randomization to initiation of the second anti-cancer systemic therapy for CRPC, up to 10 years
Efficacy of first subsequent anti-cancer systemic therapy for CRPC	Efficacy of subsequent anti-cancer systemic therapy for CRPC will be defined as the time from first anti-cancer systemic therapy for CRPC to disease progression or death from any cause, whichever comes first.	From first anti-cancer systemic therapy for CRPC to disease progression or death, up to 10 years
Efficacy of second subsequent anti-cancer systemic therapy for CRPC	Efficacy of second subsequent anti-cancer systemic therapy for CRPC will be defined as the time from second anti-cancer systemic therapy for CRPC to disease progression or death from any cause, whichever comes first.	Fromsecond anti-cancer systemic therapy for CRPC to disease progression or death, up to 10 years

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Novartis
• Investigators: Study Chair: Karim FIZAZI, MD, Gustave Roussy, VILLEJUIF; Study Chair: Gwenaelle GRAVIS, MD, IPC, Marseille

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2024
• Primary Completion (Estimated): February 1, 2033
• Study Completion (Estimated): August 1, 2039

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: July 3, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: PSA; 177Lu-PSMA-617; Prostatic Diseases; Hormones; Genital Diseases, Male
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Prednisone
• Other Study ID Numbers: UC-GTG-2301 (GETUG-AFU 42); 2022-502408-57-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD can be shared upon request to the sponsor
• IPD Sharing Time Frame: After primary analysis until end of trial
• IPD Sharing Access Criteria: Steering committee approval
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No