protocolSection identificationModule nctId: NCT06364631, orgStudyIdInfo id: 2023-503317-29-00, secondaryIdInfos id: 2023/3764, type: OTHER, domain: CSET number, briefTitle: CARE1 Pragmatic Clinical Trial, acronym: CARE1, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-04-12, primaryCompletionDateStruct date: 2032-05-05, completionDateStruct date: 2032-05-05, studyFirstPostDateStruct date: 2024-04-15, lastUpdatePostDateStruct date: 2024-04-19, sponsorCollaboratorsModule leadSponsor name: Gustave Roussy, Cancer Campus, Grand Paris, class: OTHER, collaborators name: European Commission, collaborators name: CRIS Cancer Foundation, collaborators name: National Cancer Institute, France, collaborators name: Rennes University Hospital, collaborators name: University Hospital, Essen, collaborators name: Fundació Privada Institut d'Investigació Oncològica de Vall d'Hebron, collaborators name: The Netherlands Cancer Institute, collaborators name: Servicio Madrileño de Salud, Madrid, Spain, collaborators name: Hospital Universitario 12 de Octubre, collaborators name: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, collaborators name: Medical University of Vienna, collaborators name: FAKULTNI NEMOCNICE OLOMOUC, collaborators name: International Kidney Cancer Coalition, collaborators name: Association pour la Recherche sur les Tumeurs du Rein, collaborators name: Resilience, collaborators name: PRIMAA, collaborators name: Queen Mary University of London, descriptionModule briefSummary: Systemic therapy for renal cell carcinoma (RCC) relies on 2 classes of agents: anti-angiogenic targeted therapy (Vascular endothelial growth factor Tyrosine Kinase Inhibitor- VEGFR TKI) and immune checkpoint inhibitor (ICI), targeting either PD1/PDL1 axis or CTLA4. Combination therapy is SOC for clear cell RCC in all guidelines with either ICI-ICI or ICI-VEGFR TKI. However, no head-to-head comparison have been performed between the 2 approaches and patients are treated based on physician decision without clinical /biomarker factors to guide treatment selection. PDL1 staining is, to date, the biomarker that has demonstrated its ability to enrich for overall survival benefit favoring ICI-ICI strategy in PDL1(+) and ICI-VEGFR TKI in PDL1(-) patients.Study design has been developed to demonstrate that ICI-ICI is superior to ICI-VEGFR TKI in prolonging Overall Survival (OS) for PDL1(+) patients and to demonstrate that ICI-VEGFR TKI is superior to ICI-ICI in prolonging Progression Free Survival (PFS) and OS for PDL1(-) patients., conditionsModule conditions: Metastatic Kidney Cancer, conditions: Metastatic Kidney Carcinoma, designModule studyType: INTERVENTIONAL, phases: PHASE3, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: International, multicenter, open-label, randomized, controlled Phase 3 trial - 2 arms (A and B), primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 1250, type: ESTIMATED, armsInterventionsModule interventions name: Nivolumab, interventions name: Ipilimumab, interventions name: Pembrolizumab, interventions name: Cabozantinib, interventions name: Axitinib, interventions name: Lenvatinib, outcomesModule primaryOutcomes measure: Overall Survival (OS)., secondaryOutcomes measure: Progression-free survival according to RECIST 1.1, secondaryOutcomes measure: Objective Response Rate (ORR) according to RECIST 1.1, secondaryOutcomes measure: Quality of Life via questionnaire EQ-5D-5L, secondaryOutcomes measure: Quality of Life via questionnaire NNCCN/FACT Kidney Cancer Symptom Index (NFKSI), secondaryOutcomes measure: Quality of Life via questionnaire Kidney Symptom Index (KSI), secondaryOutcomes measure: Duration of Treatment, secondaryOutcomes measure: Time to treatment discontinuation (TTD), secondaryOutcomes measure: Treatment-free survival (TFS), secondaryOutcomes measure: Time to subsequent systemic anticancer therapy (TTSST), secondaryOutcomes measure: Incidence of AE's, secondaryOutcomes measure: Health Economic evaluation: healthcare costs [France & Netherlands only], secondaryOutcomes measure: Health Economic evaluation: cost-utility [France & Netherlands only], eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Gustave Roussy, status: RECRUITING, city: Villejuif, zip: 94805, country: France, contacts name: Laurence ALBIGES, MD, PhD, role: CONTACT, phone: +33 (0)1 42 11 66 90, email: laurence.albiges@gustaveroussy.fr, geoPoint lat: 48.7939, lon: 2.35992, hasResults: False