[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100278260":3},{"organization":4,"armGroups":7,"interventions":20,"overallOfficials":35,"centralContacts":26,"locations":39,"responsibleParty":290,"collaborators":26,"id":293,"slug":294,"hasResults":295,"nctId":296,"briefTitle":297,"officialTitle":298,"acronym":299,"eligibilityCriteria":300,"healthyVolunteers":295,"sex":301,"minAge":302,"maxAge":26,"enrollmentInfo":303,"targetDuration":26,"studyType":306,"phases":307,"briefSummary":309,"conditions":310,"keywords":312,"overallStatus":314,"whyStopped":26,"lastUpdateSubmitDate":315,"lastUpdatePostDateStruct":316,"startDateStruct":318,"completionDateStruct":320,"leadSponsor":322,"locationsCount":323},{"fullName":5,"class":6},"University Hospital, Essen","OTHER",[8,16],{"label":9,"type":10,"description":11,"interventionNames":12},"Arm A","EXPERIMENTAL","After a 3 months run-in period with vemurafenib and cobimetinib \\[960 mg vemurafenib twice daily (BID), 28\u002F0; 60 mg cobimetinib daily (QD), 21\u002F7\\], all patients who do not show disease progression or definite treatment interruption (e.g. due to unacceptable toxicity) for more than 28 days will be randomized.\n\nFurther treatment with vemurafenib and cobimetinib (960 mg vemurafenib BID, 28\u002F0; 60 mg cobimetinib QD, 21\u002F7).\n\nAfter progression of disease patients in Arm A will subsequently receive atezolizumab treatment (1200 mg\u002F q3w).",[13,14,15],"Drug: Vemurafenib","Drug: Cobimetinib","Drug: Atezolizumab",{"label":17,"type":10,"description":18,"interventionNames":19},"Arm B","After a 3 months run-in period with vemurafenib and cobimetinib (960 mg vemurafenib BID, 28\u002F0; 60 mg cobimetinib QD, 21\u002F7), all patients who do not show disease progression or definite treatment interruption (e.g. due to unacceptable toxicity) for more than 28 days will be randomized.\n\nFurther treatment with atezolizumab. Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on day 1 of each 21 day-cycle.\n\nAfter progression of disease patients in Arm B will cross back to vemurafenib and cobimetinib treatment (960 mg vemurafenib BID, 28\u002F0; 60 mg cobimetinib QD, 21\u002F7).",[13,14,15],[21,27,31],{"type":22,"name":23,"description":24,"armGroupLabels":25,"otherNames":26},"DRUG","Vemurafenib","960 mg vemurafenib BID until progression or unacceptable toxicity develops",[9,17],null,{"type":22,"name":28,"description":29,"armGroupLabels":30,"otherNames":26},"Cobimetinib","60 mg cobimetinib QD, 21\u002F7 until progression or unacceptable toxicity develops",[9,17],{"type":22,"name":32,"description":33,"armGroupLabels":34,"otherNames":26},"Atezolizumab","1200 mg atezolizumab administered intravenously on day 1 of each 21 day-cycle. Will be given until progression or unacceptable toxicity develops",[9,17],[36],{"name":37,"affiliation":5,"role":38},"Dirk Schadendorf, Prof. Dr.","PRINCIPAL_INVESTIGATOR",[40,52,61,70,79,88,100,109,118,128,138,147,156,165,174,183,187,196,205,214,223,232,241,250,259,268,279],{"facility":41,"status":26,"city":42,"state":26,"zip":43,"country":44,"countryCode":45,"cosmosGeoPoint":46,"geoPoint":51,"contacts":26},"Hôpital Ambroise-Paré","Boulogne-Billancourt","92104","France","FR",{"type":47,"coordinates":48},"Point",[49,50],2.24128,48.83545,{"lat":50,"lon":49},{"facility":53,"status":26,"city":54,"state":26,"zip":55,"country":44,"countryCode":45,"cosmosGeoPoint":56,"geoPoint":60,"contacts":26},"Hospital Claude Huriez","Lille","59000",{"type":47,"coordinates":57},[58,59],3.05512,50.63391,{"lat":59,"lon":58},{"facility":62,"status":26,"city":63,"state":26,"zip":64,"country":44,"countryCode":45,"cosmosGeoPoint":65,"geoPoint":69,"contacts":26},"Hôpital de la Timone","Marseille","13885",{"type":47,"coordinates":66},[67,68],5.38107,43.29695,{"lat":68,"lon":67},{"facility":71,"status":26,"city":72,"state":26,"zip":73,"country":44,"countryCode":45,"cosmosGeoPoint":74,"geoPoint":78,"contacts":26},"CHU de Nantes","Nantes","44093",{"type":47,"coordinates":75},[76,77],-1.55336,47.21725,{"lat":77,"lon":76},{"facility":80,"status":26,"city":81,"state":26,"zip":82,"country":44,"countryCode":45,"cosmosGeoPoint":83,"geoPoint":87,"contacts":26},"Centre Hospitalier Lyon Sud","Pierre-Bénite","69310",{"type":47,"coordinates":84},[85,86],4.82424,45.70359,{"lat":86,"lon":85},{"facility":89,"status":26,"city":90,"state":91,"zip":92,"country":93,"countryCode":94,"cosmosGeoPoint":95,"geoPoint":99,"contacts":26},"National Centre for Tumour Diseases (NCT)","Heidelberg","Baden-Wurttemberg","69120","Germany","DE",{"type":47,"coordinates":96},[97,98],8.69079,49.40768,{"lat":98,"lon":97},{"facility":101,"status":26,"city":102,"state":91,"zip":103,"country":93,"countryCode":94,"cosmosGeoPoint":104,"geoPoint":108,"contacts":26},"SLK-Kliniken Heilbronn GmbH","Heilbronn","74078",{"type":47,"coordinates":105},[106,107],9.22054,49.13995,{"lat":107,"lon":106},{"facility":110,"status":26,"city":111,"state":91,"zip":112,"country":93,"countryCode":94,"cosmosGeoPoint":113,"geoPoint":117,"contacts":26},"University Hospital Mannheim, Clinic for Dermatology","Mannheim","68167",{"type":47,"coordinates":114},[115,116],8.46694,49.4891,{"lat":116,"lon":115},{"facility":119,"status":26,"city":120,"state":121,"zip":122,"country":93,"countryCode":94,"cosmosGeoPoint":123,"geoPoint":127,"contacts":26},"University Hospital Essen, Department of Dermatology, Skin Cancer Center","Essen","North Rhine-Westphalia","45122",{"type":47,"coordinates":124},[125,126],7.01228,51.45657,{"lat":126,"lon":125},{"facility":129,"status":26,"city":130,"state":131,"zip":132,"country":93,"countryCode":94,"cosmosGeoPoint":133,"geoPoint":137,"contacts":26},"HELIOS Klinikum Erfurt","Erfurt","Thuringia","99089",{"type":47,"coordinates":134},[135,136],11.03536,50.97734,{"lat":136,"lon":135},{"facility":139,"status":26,"city":140,"state":26,"zip":141,"country":93,"countryCode":94,"cosmosGeoPoint":142,"geoPoint":146,"contacts":26},"Charité-Universitätsmedizin Berlin","Berlin","10117",{"type":47,"coordinates":143},[144,145],13.41053,52.52437,{"lat":145,"lon":144},{"facility":148,"status":26,"city":149,"state":26,"zip":150,"country":93,"countryCode":94,"cosmosGeoPoint":151,"geoPoint":155,"contacts":26},"Elbe Kliniken Stade - Buxtehude","Buxtehude","21614",{"type":47,"coordinates":152},[153,154],9.68968,53.46994,{"lat":154,"lon":153},{"facility":157,"status":26,"city":158,"state":26,"zip":159,"country":93,"countryCode":94,"cosmosGeoPoint":160,"geoPoint":164,"contacts":26},"Universitätsklinikum Köln","Cologne","50937",{"type":47,"coordinates":161},[162,163],6.95,50.93333,{"lat":163,"lon":162},{"facility":166,"status":26,"city":167,"state":26,"zip":168,"country":93,"countryCode":94,"cosmosGeoPoint":169,"geoPoint":173,"contacts":26},"Universitätsklinik Dresden","Dresden","01307",{"type":47,"coordinates":170},[171,172],13.73832,51.05089,{"lat":172,"lon":171},{"facility":175,"status":26,"city":176,"state":26,"zip":177,"country":93,"countryCode":94,"cosmosGeoPoint":178,"geoPoint":182,"contacts":26},"Medizinische Hochschule Hannover","Hanover","30625",{"type":47,"coordinates":179},[180,181],9.73322,52.37052,{"lat":181,"lon":180},{"facility":184,"status":26,"city":185,"state":26,"zip":186,"country":93,"countryCode":94,"cosmosGeoPoint":26,"geoPoint":26,"contacts":26},"Universitätsklinikum des Saarlandes","Homburg\u002FSaar","66421",{"facility":188,"status":26,"city":189,"state":26,"zip":190,"country":93,"countryCode":94,"cosmosGeoPoint":191,"geoPoint":195,"contacts":26},"Universitäts-Hautklinik Kiel","Kiel","24105",{"type":47,"coordinates":192},[193,194],10.13489,54.32133,{"lat":194,"lon":193},{"facility":197,"status":26,"city":198,"state":26,"zip":199,"country":93,"countryCode":94,"cosmosGeoPoint":200,"geoPoint":204,"contacts":26},"Universitätsklinikum Leipzig","Leipzig","04103",{"type":47,"coordinates":201},[202,203],12.37129,51.33962,{"lat":203,"lon":202},{"facility":206,"status":26,"city":207,"state":26,"zip":208,"country":93,"countryCode":94,"cosmosGeoPoint":209,"geoPoint":213,"contacts":26},"Gesellschaft für Klinische Forschung Ludwigshafen mbH","Ludwigshafen","67063",{"type":47,"coordinates":210},[211,212],9.06138,47.81663,{"lat":212,"lon":211},{"facility":215,"status":26,"city":216,"state":26,"zip":217,"country":93,"countryCode":94,"cosmosGeoPoint":218,"geoPoint":222,"contacts":26},"Universitätsklinikum Schleswig-Holstein","Lübeck","23538",{"type":47,"coordinates":219},[220,221],10.68729,53.86893,{"lat":221,"lon":220},{"facility":224,"status":26,"city":225,"state":26,"zip":226,"country":93,"countryCode":94,"cosmosGeoPoint":227,"geoPoint":231,"contacts":26},"Universitätsklinikum Mainz","Mainz","55131",{"type":47,"coordinates":228},[229,230],8.28008,49.98185,{"lat":230,"lon":229},{"facility":233,"status":26,"city":234,"state":26,"zip":235,"country":93,"countryCode":94,"cosmosGeoPoint":236,"geoPoint":240,"contacts":26},"Johannes Wesling Klinikum Minden","Minden","32429",{"type":47,"coordinates":237},[238,239],8.91455,52.28953,{"lat":239,"lon":238},{"facility":242,"status":26,"city":243,"state":26,"zip":244,"country":93,"countryCode":94,"cosmosGeoPoint":245,"geoPoint":249,"contacts":26},"Klinikum der Universität München","München","80337",{"type":47,"coordinates":246},[247,248],13.31243,51.60698,{"lat":248,"lon":247},{"facility":251,"status":26,"city":252,"state":26,"zip":253,"country":93,"countryCode":94,"cosmosGeoPoint":254,"geoPoint":258,"contacts":26},"Universitätsklinikum Tübingen","Tübingen","72076",{"type":47,"coordinates":255},[256,257],9.05222,48.52266,{"lat":257,"lon":256},{"facility":260,"status":26,"city":261,"state":26,"zip":262,"country":93,"countryCode":94,"cosmosGeoPoint":263,"geoPoint":267,"contacts":26},"Uniklinikum Würzburg","Würzburg","97080",{"type":47,"coordinates":264},[265,266],9.95121,49.79391,{"lat":266,"lon":265},{"facility":269,"status":26,"city":270,"state":26,"zip":271,"country":272,"countryCode":273,"cosmosGeoPoint":274,"geoPoint":278,"contacts":26},""LAIKO" General Hospital of Athens","Athens","11527","Greece","GR",{"type":47,"coordinates":275},[276,277],23.72784,37.98376,{"lat":277,"lon":276},{"facility":280,"status":26,"city":281,"state":26,"zip":282,"country":283,"countryCode":284,"cosmosGeoPoint":285,"geoPoint":289,"contacts":26},"Military Medical Academy","Belgrade","11000","Serbia","RS",{"type":47,"coordinates":286},[287,288],20.46513,44.80401,{"lat":288,"lon":287},{"type":38,"investigatorFullName":291,"investigatorTitle":292,"investigatorAffiliation":5,"oldNameTitle":26,"oldOrganization":26},"Prof. Dr. med. Dirk Schadendorf","Prof. Dr. med.","100278260","phase-2-evaluating-the-efficacy-and-safety-of-a-sequencing-schedule-of-cobimetinib-plus-vemurafenib-followed-by-immunotherapy-with-an-anti--pd-l1-antibody-in-patients-with-unresectable-or-metastatic-braf-v600-mutant-melanoma-100278260",false,"NCT02902029","Evaluating the Efficacy and Safety of a Sequencing Schedule of Cobimetinib Plus Vemurafenib Followed by Immunotherapy With an Anti- PD-L1 Antibody in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma","A Phase II, Open-label, Randomized-controlled Trial Evaluating the Efficacy and Safety of a Sequencing Schedule of Cobimetinib Plus Vemurafenib Followed by Immunotherapy With an Anti- PD-L1 Antibody Atezolizumab for the Treatment in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma","ImmunoCobiVem","Inclusion Criteria:\n\n* Be willing and able to provide written informed consent for the trial.\n* Male or female patient being ≥18 years of age on day of signing informed consent.\n* Histologically confirmed diagnosis of locally advanced, unresectable or metastatic melanoma AJCC (unresectable stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c) without active or untreated brain metastases; all known CNS lesions must have been treated with stereotactic therapy or surgery at least 4 weeks prior to the first dose of trial treatment AND the patient must be without evidence of clinical or radiographic disease progression in the CNS for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms must have returned to baseline, the patient must have no evidence of new or enlarging brain metastases, and the patient must not have used steroids for at least 3 weeks prior to trial treatment.\n* No previous therapy for the advanced or metastatic stage. Prior adjuvant therapy is permitted (e.g. Interferon, Interleukin-2-therapy, chemo- or radiotherapy). Prior adjuvant therapy has to be terminated (last dose) at least 28 days before enrolment. Patients who are in follow-up period of a clinical trial in adjuvant setting and progressing may be enrolled \u002F randomized.\n* Measurable disease, i.e., present with at least one measurable lesion per RECIST, version 1.1, for the definition of a measureable lesion.\n* Presence of BRAF mutation (V600) in tumor tissue.\n* Performance status of 0 or 1 on the ECOG Performance Scale.\n* Adequate organ function.\n* Adequate cardiac function.\n* Able to take oral medications.\n* Female subject of childbearing potential should have a negative pregnancy test within 72 hours prior to receiving the first dose of study medication.\n* Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use a highly effective form of contraception according to CTFG during the course of this study and for at least 6 months after completion of study therapy.\n\nExclusion Criteria:\n\n* Use of any investigational or non-registered product within the 30 days before registration.\n* Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study Day 1.\n* Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).\n* Prior therapy with a BRAF inhibitor (including but not limited to vemurafenib, dabrafenib, encorafenib and \u002F or MEK inhibitor\n* Prior major surgery.\n* Known additional malignancy that is progressing or requires active treatment within 5 years prior to the study.\n* Known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis.\n* History of leptomeningeal metastases.\n* History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to RVO or CSR.\n* History of retinal degenerative disease.\n* History of allogenic bone marrow transplantation or organ transplantation.\n* History of Gilbert's syndrome.\n* Impaired cardiovascular function or clinically significant cardiovascular diseases.\n* Uncontrolled arterial hypertension despite medical treatment.\n* Impairment of gastrointestinal function or gastrointestinal disease.\n* Evidence of interstitial lung disease or active, non-infectious pneumonitis.\n* Active infection requiring systemic therapy.\n* Positive test for Human Immunodeficiency Virus (HIV).\n* Positive test for Hepatitis B or Hepatitis C.\n* Known hypersensitivity reaction to any of the components of study treatment.\n* Medical, psychiatric, cognitive or other conditions, including known alcohol or drug abuse.\n* Patients having received a live, attenuated vaccine within 4 weeks prior to the first dose of trial treatment.\n* Legal incapacity or limited legal capacity.","ALL","18 Years",{"count":304,"type":305},186,"ACTUAL","INTERVENTIONAL",[308],"PHASE2","Most patients with locally advanced or metastatic tumors succumb to their disease. Thus, there is a substantial need for novel therapeutic strategies to improve the outcome for patients with advanced or metastatic melanoma. Targeting the the Ras\u002FRaf signalling pathway by BRAF and MEK inhibition as well as targeting immunologic checkpoint control with an antiPD-L1 antibody have emerged as treatment option.\n\nIn this study the best timing for sequential use of both treatment options (BRAF\u002FMEK inhibition and antiPD-L1 antibody) in patients with unresectable or metastatic BRAFV600 mutant melanoma will be assessed.",[311],"Malignant Melanoma",[313],"unresectable stage IIIB, IIIC, IV melanoma","COMPLETED","2025-04-06",{"date":317,"type":305},"2025-04-09",{"date":319,"type":26},"2016-11",{"date":321,"type":305},"2024-03",{"name":5,"class":6},27]