protocolSection identificationModule nctId: NCT06282588, orgStudyIdInfo id: CTO21042GZA, briefTitle: Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers, acronym: THUNDER, statusModule overallStatus: RECRUITING, startDateStruct date: 2023-12-13, primaryCompletionDateStruct date: 2030-07-31, completionDateStruct date: 2030-12-31, studyFirstPostDateStruct date: 2024-02-28, lastUpdatePostDateStruct date: 2024-02-28, sponsorCollaboratorsModule leadSponsor name: Cancer Research Antwerp, class: OTHER, collaborators name: Bayer, collaborators name: Veracyte, Inc., descriptionModule briefSummary: This Investigator-initiated, Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers (THUNDER) study will be conducted in subjects with high-risk localized or locally advanced prostate cancer (PCa). The study contains both a randomized Phase 3 treatment intensification study, as well as a treatment de-intensification non-randomized Phase 2 study. The aim of the THUNDER study is to improve the outcome of high-risk PCa by improved risk stratification. Novel radiotracers and a genomic classifier (Decipher) will be used to guide treatment decisions, instead of standard imaging which is limited by lower sensitivity and specificity.The hypothesis for the study is that treatment intensification based on a positive PSMA PET/ CT scan or Decipher high score (\> 0.6) improves time to new metastases detected on PSMA PET/ CT in high-risk PCa. In patients who are PSMA PET/ CT negative with a low/ intermediate Decipher score (≤ 0.6), it is hypothesized that treatment de-intensification will improve patient quality of life while maintaining a good oncological outcome.The study will be conducted at multiple centers across Europe. Participation in the study will comprise a screening period, where the screening assessments must be completed before subjects are enrolled and randomized (only for Phase 3 subjects). Eligible, consenting subjects will then undergo treatment according to their assigned study phase and treatment group, to occur over up to 96 weeks (24 months) with a post-treatment follow-up period to monitor safety and efficacy. The study will be closed when 96 events have been registered for the primary endpoint, which is expected to be at 7-8 years from the time of randomization of the first subject., conditionsModule conditions: Prostate Cancer, designModule studyType: INTERVENTIONAL, phases: PHASE2, phases: PHASE3, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Phase 2: non randomised, 1 treatment arm, open label Phase 3: randomized 1:1 between two treatment arms, blinded, primaryPurpose: TREATMENT, maskingInfo masking: QUADRUPLE, maskingDescription: Phase 3 trial: blinded Phase 2 trial: open label, whoMasked: PARTICIPANT, whoMasked: CARE_PROVIDER, whoMasked: INVESTIGATOR, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 493, type: ESTIMATED, armsInterventionsModule interventions name: Darolutamide, interventions name: Darolutamide matched placebo, interventions name: Radiotherapy, interventions name: Zoladex 3.6Mg Implant, interventions name: Zoladex LA, interventions name: Decapeptyl sustained release 22.5 mg, interventions name: Decapeptyl sustained release 11.25 mg, interventions name: Depo-Eligard 45 mg, interventions name: Depo-Eligard 22.5 mg, interventions name: Depo-Eligard 7.5 mg, interventions name: Firmagon 120 MG Injection, interventions name: Firmagon 80 MG Injection, interventions name: Docetaxel, outcomesModule primaryOutcomes measure: Phase 3: PSMA PET metastasis free survival (ppMFS), primaryOutcomes measure: Phase 2: quality of life (sexual subdomain), primaryOutcomes measure: Phase 2: quality of life (hormonal subdomain), secondaryOutcomes measure: Overall survival, secondaryOutcomes measure: Prostate-cancer specific survival, secondaryOutcomes measure: Biochemical progression-free survival, secondaryOutcomes measure: Time to next systemic therapy, secondaryOutcomes measure: Frequency and severity of adverse events, eligibilityModule sex: MALE, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: GZA Sint-Augustinus, status: RECRUITING, city: Wilrijk, state: Antwerp, zip: 2610, country: Belgium, contacts name: Piet Ost, MD, PhD, role: CONTACT, email: cancertrials@gza.be, contacts name: Piet Ost, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 51.16734, lon: 4.39513, locations facility: OLVZ Aalst, status: NOT_YET_RECRUITING, city: Aalst, zip: 9300, country: Belgium, contacts name: Samuel Br, role: CONTACT, contacts name: Samuel Bral, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 50.93604, lon: 4.0355, locations facility: AZ Sint-Jan, status: NOT_YET_RECRUITING, city: Brugge, zip: 8000, country: Belgium, contacts name: Sabine Meersschout, role: CONTACT, contacts name: Sabine Meersschout, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 51.20892, lon: 3.22424, locations facility: Saint Luc, status: NOT_YET_RECRUITING, city: Bruxelles, zip: 1200, country: Belgium, contacts name: Ad Vanderm, role: CONTACT, contacts name: Ad Vandermeulen, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 50.85045, lon: 4.34878, locations facility: UZA, status: NOT_YET_RECRUITING, city: Edegem, zip: 2600, country: Belgium, contacts name: Karen Fransis, role: CONTACT, contacts name: Karen Fran, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 51.15662, lon: 4.44504, locations facility: UZ Gent, status: NOT_YET_RECRUITING, city: Gent, zip: 9000, country: Belgium, contacts name: Valérie Fonteyne, role: CONTACT, contacts name: Valérie Fonteyne, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 51.05, lon: 3.71667, locations facility: AZ Sint-Lucas, status: NOT_YET_RECRUITING, city: Gent, zip: 900, country: Belgium, contacts name: Lien Van De Voorde, role: CONTACT, contacts name: Lien Van De Voor, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 51.05, lon: 3.71667, locations facility: AZ Groeninge, status: NOT_YET_RECRUITING, city: Kortrijk, zip: 8500, country: Belgium, contacts name: Nick Liefhooghe, role: CONTACT, contacts name: Nick Liefhooghe, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 50.82803, lon: 3.26487, locations facility: CHU Liège, status: NOT_YET_RECRUITING, city: Liège, zip: 4000, country: Belgium, contacts name: Brieuc Suatois, role: CONTACT, contacts name: Brieuc Sautois, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 50.63373, lon: 5.56749, locations facility: AZ Delta, status: NOT_YET_RECRUITING, city: Roeselare, zip: 8800, country: Belgium, contacts name: Benedikt Engels, role: CONTACT, contacts name: Benedikt Enge, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 50.94653, lon: 3.12269, locations facility: VITAZ, status: NOT_YET_RECRUITING, city: Sint-Niklaas, zip: 9100, country: Belgium, contacts name: Bart De Troyer, role: CONTACT, contacts name: Bart De Troyer, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 51.16509, lon: 4.1437, hasResults: False