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

NCT06625970 | Recruiting Phase 3 DMC

• 2 other identifiers: UC-GTG-23102023-509787-15-00
• Study Type: interventional
• Target: 700
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

High Risk Prostate Carcinoma; Prostate Cancer

Keywords

HPRC, PSMA-PET, Prostate Cancer, High-Risk

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Clinical Progression-Free Survival

  From randomization to disease progression, up to 8.5 years

• Biochemical Progression-Free Survival

  From randomization to PSA relapse or death, up to 8.5 years

• Time to local relapse

  From randomization to local disease progression, up to 8.5 years

• Prostate Cancer-Specific Survival (PCSS)

  From randomization to death due to prostate cancer, up to 8.5 years

• Overall Survival (OS)

  From randomization to death, up to 20 years

Study Arms (4)

Arm A (Standard arm)

OTHER

ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy

Drug: ADT (Standard of Care); Radiation: radiotherapy

Arm B (Experimental arm):

EXPERIMENTAL

ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy + darolutamide

Drug: Darolutamide; Drug: ADT (Standard of Care); Radiation: radiotherapy

Arm C (Experimental arm):

EXPERIMENTAL

ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT

Radiation: Stereotactic Body RadioTherapy (SBRT); Drug: ADT (Standard of Care); Radiation: radiotherapy

Arm D (Experimental arm):

EXPERIMENTAL

ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT + darolutamide

Drug: Darolutamide; Radiation: Stereotactic Body RadioTherapy (SBRT); Drug: ADT (Standard of Care); Radiation: radiotherapy

Interventions

Darolutamide DRUG

Pharmaceutical form: 300 mg tablets Administration route: oral (PO) Posology: 600 mg twice daily (BID)

Arm B (Experimental arm):; Arm D (Experimental arm):

Stereotactic Body RadioTherapy (SBRT) RADIATION

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.

Arm C (Experimental arm):; Arm D (Experimental arm):

ADT (Standard of Care) DRUG

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).

Also known as: LHRH agonists, LHRH antagonists

Arm A (Standard arm); Arm B (Experimental arm):; Arm C (Experimental arm):; Arm D (Experimental arm):

radiotherapy RADIATION

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.

Also known as: Normo-fractionated radiotherapy, Hypo-fractionated radiotherapy, intensity modulated radiotherapy (IMRT), whole pelvic nodal radiotherapy (WPRT)

Arm A (Standard arm); Arm B (Experimental arm):; Arm C (Experimental arm):; Arm D (Experimental arm):

Eligibility Criteria

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

You may qualify if:

• 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
• Men, 18 years ≤ Age ≤ 80 years
• ECOG performance status of 0 or 1
• No significant co-morbidities that might prevent long-term follow-up
• Histologically confirmed adenocarcinoma of the prostate
• 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
• Prostate size on MRI \<100 cc
• Absolute neutrophil count ≥ 1.5 x 10⁹/L
• Platelet count ≥100 x 10⁹/L
• Haemoglobin ≥90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomization)
• 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

You may not qualify if:

• 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
• 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
• 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)
• 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
• 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
• Uncontrolled diabetes mellitus
• Current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment)
• Gastrointestinal disorder or procedure, which expects to interfere significantly with absorption of study treatment. Severe GI disorders precluding pelvic irradiation
• 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)
• Other prior malignancy within the last 3 years, except basal cell skin cancer
• Known hypersensitivity to the study treatment or any of its ingredients.
• 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
• Previous treatment for prostate cancer (surgery or radiotherapy) or previous pelvic irradiation that would make prostate/pelvis radiotherapy impossible
• 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
• Prior treatment with second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor

Sponsors & Collaborators

• UNICANCER: lead
• Bayer: collaborator

Study Sites (6)

Clinique Pasteur Lanroze - Brest

Brest, France

RECRUITING

Centre Georges Francois Leclerc

Dijon, France

RECRUITING

Groupe Hospitalier Paris Saint-Joseph

Paris, France

RECRUITING

CHU Saint-Etienne

Saint-Etienne, France

RECRUITING

Gustave Roussy, Cancer Campus, Grand Paris

Villejuif, 94800, France

RECRUITING

CHU Martinique

Fort-de-France, Martinique

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide; Radiosurgery; Androgen Antagonists; Standard of Care; Radiotherapy; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted

Study Officials

• 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 CHAIR

Central Study Contacts

Carine LA

CONTACT

014-423-0404; c-la@unicancer.fr

Catherine LEGER

CONTACT

c-leger@unicancer.fr

Study Design

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

Model Details: 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 Patients will be stratified according to the number of risk factors (2 vs. 3) and the presence of a dominant intraprostatic lesion prostate imaging-reporting and data system (PI-RADS) 5 (yes vs no) and investigational site.

Study Record Dates

• First Submitted: October 2, 2024
• First Posted: October 3, 2024
• Study Start: April 10, 2025
• Primary Completion (Estimated): October 1, 2033
• Study Completion (Estimated): October 1, 2045
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); MA (1)