Study Evaluating the Efficacy and Safety of Darolutamide and Stereotactic Dose Escalated Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse (PEACE 7)

A Randomized Phase III Trial With a Factorial Design Evaluating the Efficacy and Safety of Darolutamide and Stereotactic Dose Escalated Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse, From the Prostate Cancer Consortium in Europe (PEACE)

PEACE 7 is an international, multicenter, randomized, open-label phase III study that aims at evaluating the efficacy and safety of darolutamide and of stereotactic dose escalated prostate radiotherapy in patients with localised prostate cancer and high-risk features of relapse (defined as patients with at least 2 high-risk criteria from National Comprehensive Cancer Network (NCCN) classification) using a factorial (2x2) design.

The primary objective of this study is to assess the efficacy of darolutamide and of a stereotactic dose escalated radiotherapy targeting prostate in combination with ADT and pelvic nodal radiotherapy in terms of metastasis-free survival (MSF).

Patients will be randomized (1:1:1:1) to receive either:

• Arm A (Standard arm): ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy
• Arm B (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy + darolutamide
• Arm C (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT
• Arm D (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT + darolutamide

Patient will receive systemic treatments (ADT and/or darolutamide) during 2 years where visits on site are planned at D45, D90, D180 and then every 3 months for checkups and follow prostate specific antigen (PSA) level.

Metastasis-free survival (MFS) is defined as the time interval from randomization to the date of the appearance of metastasis (on next generation imaging) or death (from any cause), whichever occurs first. Radiographic evaluation will be carried out at the time of biochemical failure (Phoenix criteria) or in case of clinical suspicion. After biochemical failure (Phoenix criteria) radiographic evaluation on next generation imaging (prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan (any European Medicines Agency (EMA) approved PSMA tracer)) will be performed every 6 months until a metastatic site of relapse is identified and will be repeated at each subsequent PSA progression.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; High Risk Prostate Carcinoma
• Intervention / Treatment: Drug: ADT (Standard of Care); Radiation: radiotherapy; Drug: Darolutamide; Radiation: Stereotactic Body RadioTherapy (SBRT)

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Carine LA; Phone Number: 014-423-0404; Email: c-la@unicancer.fr
• Study Contact Backup: Name: Catherine LEGER; Email: c-leger@unicancer.fr

Study Locations

• France
  • Brest, France
    • Recruiting
    • Clinique Pasteur Lanroze - Brest
    • Contact: Ali HASBINI, MD; Phone Number: 33 2 98 31 33 29; Email: alihasbini@oncologie-brest.fr
  • Dijon, France
    • Recruiting
    • Centre Georges Francois Leclerc
    • Contact: Magali QUIVRIN, MD; Phone Number: 33 3 80 73 75 18; Email: mquivrin@cgfl.fr
  • Paris, France
    • Recruiting
    • Groupe Hospitalier Paris Saint-Joseph
    • Contact: Lionel STAUDACHER, MD; Phone Number: 33 1 44 12 75 96; Email: lstaudacher@ghpsj.fr
  • Saint-Étienne, France
    • Recruiting
    • CHU Saint-Etienne
    • Contact: Thierry REYNAUD, MD; Phone Number: +33 4 77 82 28 82; Email: thomas.reynaud@chu-st-etienne.fr
  • Villejuif, France, 94800
    • Recruiting
    • Gustave Roussy, Cancer Campus, Grand Paris
    • Contact: Pierre BLANCHARD, MD; Phone Number: 0033 1 42 11 49 31; Email: pierre.blanchard@gustaveroussy.fr
• Martinique
  • Fort-de-France, Martinique
    • Recruiting
    • CHU Martinique
    • Contact: Alexis VALLARD, MD; Phone Number: +33 6 64 03 29 82; Email: alexis.vallard@chu-martinique.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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. Men, 18 years ≤ Age ≤ 80 years
3. ECOG performance status of 0 or 1
4. No significant co-morbidities that might prevent long-term follow-up
5. Histologically confirmed adenocarcinoma of the prostate

6. Meet at least 2 of the following criteria from NCCN classification:

   • Gleason score ≥8
   • T3 or T4 disease (T3 defined by MRI is acceptable)
   • Prostate-specific antigen ≥20 ng/mL
7. Prostate size on MRI <100 cc
8. Absolute neutrophil count ≥ 1.5 x 10⁹/L
9. Platelet count ≥100 x 10⁹/L
10. Haemoglobin ≥90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomization)
11. Hepatic function: serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ≤2.5 x upper limit of normal (ULN), total bilirubin ≤1.5 x ULN
12. Creatinine ≤2.0 x ULN
13. Sexually active patients must agree to use an effective contraceptive method while on treatment and for 1 week after the final dose of investigational product
14. Patient must be affiliated to a Social Security System or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials)
15. Patient must be 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:

1. Clinically or radiologically detectable metastasis, including no evidence of pelvic lymph node metastasis on next generation imaging (PSMA PET/CT), nor enlarged pelvic lymph nodes (≥1 cm in small diameter) on MRI Note: Patients with infra-centimetric nodal disease (<1 cm in small diameter) on conventional imaging and equivocal hyperfixation on next generation imaging may be included
2. Recent history of TURP or prostate enucleation (less than 6 months) Note: patients with severe obstructive symptoms (defined as International Prostate Symptom Score (IPSS) ≥20) should be carefully evaluated to rule out the need for TURP/Prostate enucleation
3. Prior treatment for prostate cancer, including prostatectomy, except lymph node dissection (patients with PN- disease only can be accrued) or ADT (started more than 6 weeks before randomization)
4. Patient with other known concurrent severe and/or uncontrolled concurrent medical disease or infection (such as active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease) or co-morbidity, which could compromise participation in the study
5. Cardiac disease such as uncontrolled hypertension (systolic BP ≥160 mmHg or diastolic BP ≥95 mmHg; 3 consecutive measures taken 5 minutes apart), stroke, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, coronary/peripheral artery bypass graft, LVEF > grade 2
6. Uncontrolled diabetes mellitus
7. Current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment)
8. Gastrointestinal disorder or procedure, which expects to interfere significantly with absorption of study treatment. Severe GI disorders precluding pelvic irradiation
9. Known severely impaired lung function (spirometry and DLCO 70% or less of normal and O2 saturation of 88% or less at rest on room air)
10. Other prior malignancy within the last 3 years, except basal cell skin cancer
11. Known hypersensitivity to the study treatment or any of its ingredients.
12. Physical or psychological condition or any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures
13. Previous treatment for prostate cancer (surgery or radiotherapy) or previous pelvic irradiation that would make prostate/pelvis radiotherapy impossible
14. Concomitant prohibited treatment. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5. A one-week washout period is necessary for patients who are already on these treatments
15. Prior treatment with second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor
16. Use of oestrogens or 5-α reductase inhibitors or AR inhibitors
17. Acute toxicities of prior treatments and procedures not resolved to grade ≤1 or baseline before randomization
18. Prior chemotherapy or immunotherapy for prostate cancer
19. Major surgery within 28 days before randomization
20. Participation in another therapeutic trial within 30 days prior to inclusion
21. Persons deprived of their liberty or under protective custody or guardianship
22. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm A (Standard arm); ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy	Drug: ADT (Standard of Care); Androgen Deprivation Therapy (ADT) The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years. Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization).; Other Names: LHRH agonists; LHRH antagonists; Radiation: radiotherapy; Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT). Arm A and Arm B: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks). If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks. Arm C and Arm D: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks. If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks.; Other Names: Normo-fractionated radiotherapy; Hypo-fractionated radiotherapy; intensity modulated radiotherapy (IMRT); whole pelvic nodal radiotherapy (WPRT)
Experimental: Arm B (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy + darolutamide	Drug: ADT (Standard of Care); Androgen Deprivation Therapy (ADT) The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years. Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization).; Other Names: LHRH agonists; LHRH antagonists; Radiation: radiotherapy; Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT). Arm A and Arm B: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks). If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks. Arm C and Arm D: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks. If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks.; Other Names: Normo-fractionated radiotherapy; Hypo-fractionated radiotherapy; intensity modulated radiotherapy (IMRT); whole pelvic nodal radiotherapy (WPRT); Drug: Darolutamide; Pharmaceutical form: 300 mg tablets Administration route: oral (PO) Posology: 600 mg twice daily (BID)
Experimental: Arm C (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT	Drug: ADT (Standard of Care); Androgen Deprivation Therapy (ADT) The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years. Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization).; Other Names: LHRH agonists; LHRH antagonists; Radiation: radiotherapy; Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT). Arm A and Arm B: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks). If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks. Arm C and Arm D: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks. If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks.; Other Names: Normo-fractionated radiotherapy; Hypo-fractionated radiotherapy; intensity modulated radiotherapy (IMRT); whole pelvic nodal radiotherapy (WPRT); Radiation: Stereotactic Body RadioTherapy (SBRT); Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT). At study entry, each investigational site will be asked to choose one regimen (normo-fractionation or moderate hypo-fractionation) which will be applied for all patients included by the investigational site in the study. SBRT, experimental treatment, will be used as a boost in Arms C & D. The placement of 3 to 4 fiducial markers for stereotactic boost is mandatory. SBRT will be applied only on Prostate: 2 times 10 Gy delivered to the prostate with a gap of one week between each SBRT fraction.
Experimental: Arm D (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT + darolutamide	Drug: ADT (Standard of Care); Androgen Deprivation Therapy (ADT) The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years. Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization).; Other Names: LHRH agonists; LHRH antagonists; Radiation: radiotherapy; Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT). Arm A and Arm B: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks). If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks. Arm C and Arm D: If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks. If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks.; Other Names: Normo-fractionated radiotherapy; Hypo-fractionated radiotherapy; intensity modulated radiotherapy (IMRT); whole pelvic nodal radiotherapy (WPRT); Drug: Darolutamide; Pharmaceutical form: 300 mg tablets Administration route: oral (PO) Posology: 600 mg twice daily (BID); Radiation: Stereotactic Body RadioTherapy (SBRT); Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT). At study entry, each investigational site will be asked to choose one regimen (normo-fractionation or moderate hypo-fractionation) which will be applied for all patients included by the investigational site in the study. SBRT, experimental treatment, will be used as a boost in Arms C & D. The placement of 3 to 4 fiducial markers for stereotactic boost is mandatory. SBRT will be applied only on Prostate: 2 times 10 Gy delivered to the prostate with a gap of one week between each SBRT fraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis-free survival	Metastasis-free survival (MFS) is defined as the time interval from randomization to the date of the appearance of metastasis (on next generation imaging) or death (from any cause), whichever occurs first.	from randomization to the onset of metastasis or death, up to 8.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Progression-Free Survival	Clinical Progression-Free Survival (cPFS) is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Clinical disease progression is defined as metastatic relapse or proven local relapse (by either biopsy or unequivocal imaging), unequivocal nodal progression on imaging, or death (from any cause), whichever occurs first.	From randomization to disease progression, up to 8.5 years
Biochemical Progression-Free Survival	Biochemical Progression-Free Survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Biological disease progression is defined as the time interval from randomization to the date of PSA relapse or death (from any cause), whichever occurs first.	From randomization to PSA relapse or death, up to 8.5 years
Time to local relapse	Time to local relapse is defined as the time interval from randomization to the date of the appearance of the first proven local relapse (by either biopsy or unequivocal imaging).	From randomization to local disease progression, up to 8.5 years
Prostate Cancer-Specific Survival (PCSS)	Prostate Cancer-Specific Survival (PCSS) is defined as the time interval between randomization and the date of death due to prostate cancer.	From randomization to death due to prostate cancer, up to 8.5 years
Overall Survival (OS)	Overall Survival (OS) is the length of time from randomization that patients enrolled in the study are still alive	From randomization to death, up to 20 years

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Bayer
• Investigators: Study Chair: Karim Fizazi, MD, PhD, Gustave Roussy, Cancer Campus, Grand Paris; Study Chair: Pierre BLANCHARD, MD, PhD, Gustave Roussy, Cancer Campus, Grand Paris; Study Chair: Gilles CREHANGE, MD, PhD, Institut Curie

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2025
• Primary Completion (Estimated): October 1, 2033
• Study Completion (Estimated): October 1, 2045

Study Registration Dates

• First Submitted: October 2, 2024
• First Submitted That Met QC Criteria: October 2, 2024
• First Posted (Actual): October 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 21, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: HPRC, PSMA-PET, Prostate Cancer, High-Risk
• 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; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: UC-GTG-2310; 2023-509787-15-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients

Drug and device information, study documents

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