Phase III Radium 223 mCRPC-PEACE III

NCT02194842 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: EORTC-1333-GUCG2014-001787-36
• Study Type: interventional
• Target: 446
• Locations: 12 countries
• Sites: 64

Brief Summary

The primary objective of the trial is to assess if upfront combination of enzalutamide and Ra223 improves radiological progression-free survival (rPFS1) by investigator assessment compared to enzalutamide single agent in castration resistant prostate cancer (CRPC) patients metastatic to bone

Conditions

Prostate Cancer

Keywords

metastatic; prostate cancer

Outcome Measures

Primary Outcomes (2)

• radiological progression-free survival

  Radiological progression free survival (rPFS1) is defined according to the recommendations of the "Prostate-Cancer clinical trials Working Group" version 3 and referred to as the "PCWG3"; for the setting "delay/prevent" progression. An event of progression according to their definition is either of: * Objective progression of the disease according to RECIST 1.1 criteria for soft tissue lesions * A skeletal radiological progression defined as the appearance of ≥ 2 new bone lesions and for the first follow-up assessment only (i.e., within 12 weeks ± 1 week, during the flare period), a confirmatory scan performed ≥ 6 weeks later that shows a minimum of two or more additional new lesions (2+2 criterion) In this protocol: PSA progression is not considered disease progression and should NOT trigger a change of treatment. The rPFS1 endpoint is subject to a retrospective Blinded Independent Central Review

  46 months after first patient entry

• progression-free survival per Blinded Independent Central Review (PFS1B)

  PFS1 per BICR will be defined and analyzed in the same manner as the primary endpoint rPFS1 by investigator assessment. The central reviewers will provide timepoint assessments of skeletal and nonskeletal progression and determinations of respective progression dates from which PFS1 per BICR will be calculated.

  96 months after first patient entry

Secondary Outcomes (12)

• Overall survival

  63 months after first patient entry

• prostate cancer specific survival

  63 months after first patient entry

• Time to First symptomatic skeletal event (TTSSE)

  46 and 63 months after first patient entry

• Time to first skeletal progression

  46 and 63 months after first patient entry

• Time from entry to initiation of next systemic anti-neoplastic therapy (TTNT)

  46 and 63 months after first patient entry

Study Arms (2)

Enzalutamide

ACTIVE COMPARATOR

Enzalutamide will be given at a dose of 160 mg daily

Drug: Enzalutamide

Enzalutamide and Ra223

EXPERIMENTAL

Ra223 will be administered 55kBq/kg standard dose monthly for 6 months and given in combination with enzalutamide at a dose of 160 mg daily.

Drug: Ra223; Drug: Enzalutamide

Interventions

Ra223 DRUG

Enzalutamide and Ra223

Enzalutamide DRUG

Enzalutamide; Enzalutamide and Ra223

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of prostate adenocarcinoma
• Asymptomatic or mildly symptomatic (defined as short form question #3 in Brief Pain Inventory worst pain must be \< 4, see Appendix E)
• Metastatic to bone with ≥ 4 bone metastases (ambiguous areas of increased uptake on 99mTc Bone Scan (BS) should be confirmed by CT or MRI) with or without additional lymph node metastases.
• Patients with visceral metastases are not allowed. Patients with multifocal bone lesions are allowed; while patients with diffuse confluent bone lesions (superscan) are not allowed in the trial.
• Note: Patients must start treatment with a bone protecting agent (at doses used to reduce the incidence of skeletal related events) ideally before or at the time of randomization, if patient is not already on one. A minimum of two doses is recommended before the first administration of Ra223 in the experimental arm. The first administration of Ra223 should be scheduled at least 6 weeks after the first administration of bone protecting agent.
• Note: For French sites only, patients must not have undergone a PET/CT scan for restaging prostate cancer using radiopharmaceuticals such as 18F-FDG, 18F-fluoride, 18F-Fluorocholine or a PSMA (prostate-specific membrane antigen) ligand or any other tracer.
• Progressive CRPC according to Prostate Cancer Working Group 3 (PCWG3) (Ref. 22) i.e. either:
• For patients who manifest disease progression solely as a rising PSA level, PCWG3 criteria require documentation of a sequence of rising PSA values at a minimum of 1-week intervals with the last value \> 2 ng/mL
• For patients with disease progression manifest in the bone, irrespective of progression by rising PSA, PCWG3 guidelines require appearance of 2 or more new lesions. Ambiguous results should be confirmed by other imaging modalities than bone scan (e.g.: CT-scan or MRI)
• For patients with disease progression manifest at nodal sites, irrespective of progression by rising PSA, PCWG3 requires progression according to RECIST 1.1
• Ongoing androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or bilateral orchiectomy
• No known central nervous system metastases or leptomeningeal tumor spread.
• Patients must be at least 18 years old
• WHO Performance status 0-1(see Appendix C)
• Charlson score ≤ 3 (see Appendix G)

You may not qualify if:

• No known history of central nervous system metastases or leptomeningeal tumor spread.
• No significant cardiovascular disease including:
• Myocardial infarction within 6 months prior to screening
• Uncontrolled angina within 3 months prior to screening
• Congestive heart failure New York Heart Association (NYHA) class III or IV, or patients with history of congestive heart failure NYHA class III or IV in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45%
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
• Uncontrolled hypertension as indicated by a resting systolic blood pressure \> 170 mm Hg or diastolic blood pressure \> 105 mm Hg at screening
• Hypotension as indicated by systolic blood pressure \< 86 millimeters of mercury (mm Hg) at screening
• Bradycardia as indicated by a heart rate of \< 45 beats per minute on the screening ECG and on physical examination
• patients having received docetaxel for CRPC are excluded.
• No prior treatment with enzalutamide or Ra223
• No prior and concomitant treatment with Cyp17 inhibitors (abiraterone, orteronel) and ketoconazole
• No prior hemibody external radiotherapy. Patients who received other types of prior external radiotherapy are allowed provided that the bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count and platelets
• No prior therapy with other radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188)

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Bayer: collaborator
• Astellas Pharma Europe Ltd.: collaborator
• UNICANCER: collaborator
• Canadian Urologic Oncology Group: collaborator
• Latin American Cooperative Oncology Group: collaborator
• Cancer Trials Ireland: collaborator

Study Sites (64)

Hopital Universitaire Brugmann

Brussels, 1020, Belgium

Location

Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

AZ Groeninge Kortrijk

Kortrijk, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

AZ Turnhout

Turnhout, Belgium

Location

CHU Dinant Godinne - UCL Namur

Yvoir, 5530, Belgium

Location

Hospital de Amor

Barretos, 14.784-400, Brazil

Location

Hospital Erasto Gaertner

Curitiba, 81520-060, Brazil

Location

Centro Pesquisas Oncologicas

Florianópolis, 88034000, Brazil

Location

Oncocentro

Fortaleza, 60130-241, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, 90035-001, Brazil

Location

Centro de Pesquisas Clinicas em Oncologia - Hospital Sao Lucas

Porto Alegre, 90610 000, Brazil

Location

Instituto de Medicina Integral Professor Fernando Figueira - IMIP

Recife, 50070-550, Brazil

Location

Centro de Tratamentos de Tumores Botafogo

Rio de Janeiro, 22250-040, Brazil

Location

Clínica Oncológica - CLION

Salvador, 41810-570, Brazil

Location

Centro de Estudos e Pesquisa Hematologia e Oncologia

Santo André, 09060-650, Brazil

Location

Hospital Beneficencia Portuguesa

São Paulo, 01321-000, Brazil

Location

Hospital Paulistano

São Paulo, 01321-001, Brazil

Location

Sao Camilo Oncologia - Instituto Brasileiro de Controle do Cancer

São Paulo, 03.102-002, Brazil

Location

Saint John Regional Hospital

Saint John, New Brunswick, E2L 4, Canada

Location

Hamilton And District Urology Association

Hamilton, Ontario, L8N 1T8, Canada

Location

London Regional Cancer Center

London, Ontario, N6A 4L6, Canada

Location

Odette Cancer Centre - Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network - Oci Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Centre de sante et de services sociaux de Chicoutimi

Chicoutimi, Quebec, G7H 5H6, Canada

Location

CHUM - Centre Hospitalier de l'Université de Montreal - Pavillon Saint-Luc

Montreal, Quebec, H2X 3J4, Canada

Location

Chuq-Pavillon Hotel-Dieu De Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Rigshospitalet

Copenhagen, Denmark

Location

Institut de Cancerologie de l'Ouest (ICO) - Centre Paul Papin

Angers, 49055, France

Location

Centre Francois Baclesse

Caen, 14076, France

Location

Assistance Publique - Hopitaux de Paris - CHU Henri Mondor

Créteil, 94000, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut régional du Cancer Montpellier

Montpellier, 34298, France

Location

Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau

Saint-Herblain, 44805, France

Location

Hopitaux Universitaires de Strasbourg - Hôpitaux Universitaires de Strasbourg - Hôpital civil

Strasbourg, 67091, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Cork University Hospital

Cork, TI2DC4A, Ireland

Location

St. Vincent's University Hospital

Dublin, Ireland

Location

Tallaght University Hospital

Dublin, Ireland

Location

Ospedale B.Ramazzini

Carpi, 41012, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Soerlandet Sykehus-Kristiansand

Kristiansand, 4604, Norway

Location

University Hospital of North Norway

Tromsø, N-9038, Norway

Location

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, Poland

Location

Hospital Del Mar

Barcelona, 08003, Spain

Location

Vall d'Hebron Institut d'Oncologia

Barcelona, 08035, Spain

Location

Hospital Clinic Universitari de Barcelona

Barcelona, 08036, Spain

Location

Hospital De La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario QuironSalud

Madrid, 28223, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, 31008, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Oncology Institute of Southern Switzerland - Ospedale San Giovanni

Bellinzona, 6500, Switzerland

Location

Kantonsspital St Gallen

Sankt Gallen, Switzerland

Location

UniversitaetsSpital Zurich

Zurich, 8091, Switzerland

Location

United Lincolnshire Hospitals NHS Trust - Lincoln County Hospital

Lincoln, LN2 5QY, United Kingdom

Location

Royal Marsden Hospital - Chelsea, London

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, United Kingdom

Location

Related Publications (2)

• Tombal B, Saad F, Gallardo E, Soares A, Loriot Y, McDermott R, Briers E, Lagstrom M, Coens C, Poncet C, Fournier B, Gillessen S. A plain language summary of the EORTC 1333/PEACE-3 study of enzalutamide alone vs enzalutamide plus radium-223 in patients with metastatic castrationresistant prostate cancer (mCRPC) and bone metastases. Future Oncol. 2025 Dec;21(30):3845-3858. doi: 10.1080/14796694.2025.2592722. Epub 2025 Nov 28.

  PMID: 41313045 DERIVED

• Gillessen S, Tombal B, Turco F, Choudhury A, Rodriguez-Vida A, Gallardo E, Velho PI, Nole F, Cruz F, Loriot Y, McDermott R, Roumeguere T, Daugaard G, Yamamura R, Bompas E, Maroto P, Polo MH, da Trindade KM, Preto DD, Skoneczna I, Lecouvet F, Coens C, Fournier B, Saad F. Decrease in Fracture Rate with Mandatory Bone-protecting Agents in the EORTC 1333/PEACE-3 Trial Comparing Radium-223 Combined with Enzalutamide Versus Enzalutamide Alone: A Safety Analysis. Eur Urol. 2025 Mar;87(3):285-288. doi: 10.1016/j.eururo.2024.11.027. Epub 2025 Jan 17.

  PMID: 39827019 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

Radium-223; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bertrand Tombal, Prof

  Cliniques Universitaires de Saint Luc

  STUDY CHAIR

• Silke Gillessen, Prof

  Oncology Institute of Southern Switzerland - Ospedale San Giovanni

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: July 18, 2014
• Study Start: October 1, 2015
• Primary Completion: February 19, 2024
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 19, 2025

Record last verified: 2025-09

Locations

CH (3); DK (1); IE (3); CA (8); GB (4); ES (10); IT (3); PL (1); FR (8); BE (8); NO (2); BR (13)