[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100329335":3},{"organization":4,"outcomesModule":7,"designInfo":75,"detailedDescription":83,"studyPopulation":80,"armGroups":84,"interventions":98,"overallOfficials":80,"centralContacts":113,"locations":123,"responsibleParty":603,"collaborators":80,"id":605,"slug":80,"hasResults":606,"nctId":607,"briefTitle":608,"officialTitle":609,"acronym":610,"eligibilityCriteria":611,"healthyVolunteers":606,"sex":612,"minAge":613,"maxAge":80,"enrollmentInfo":614,"targetDuration":80,"studyType":617,"phases":618,"briefSummary":620,"conditions":621,"keywords":625,"overallStatus":126,"whyStopped":80,"lastUpdateSubmitDate":626,"lastUpdatePostDateStruct":627,"startDateStruct":630,"completionDateStruct":632,"leadSponsor":634,"locationsCount":635},{"fullName":5,"class":6},"Philogen S.p.A.","INDUSTRY",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":70},[9],{"measure":10,"description":11,"timeFrame":12},"Recurrence Free Survival (RFS)","Recurrence Free Survival (RFS) in a time-to-event analysis in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus the surgery and adjuvant therapy control group (Arm 2). Analysis will be performed for the \"Intention To Treat\" population.","From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months.",[14,18,21,25,29,33,36,39,42,46,50,53,57,60,63,66],{"measure":15,"description":16,"timeFrame":17},"Overall survival (OS)","Overall survival (OS) in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus surgery and adjuvant therapy (Arm 2), which will be evaluated in time to event analysis as key secondary endpoint.","From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first, assessed up to 72 months.",{"measure":19,"description":20,"timeFrame":12},"Recurrence free survival (RFS) as determined by the local investigator","A sensitivity analysis to assess ascertainment bias will be performed on recurrence free survival. For this analysis the primary analysis definition of recurrence will be split into its two components and each will be analyzed separately. The first component\u002Fdefinition will be based on the unblinded assessment performed at the site - any new lesion detected by clinical evaluation which is confirmed by histopathology (biopsy or surgical specimen) and the second component\u002Fdefinition will be based on the assessment of a new lesion detected by allowed imaging modalities in a Blinded Independent Central Review and confirmed, wherever possible, by histological analysis. Each of these components will be analyzed separately using the same statistical model as the primary endpoint. Results from the two component analyses will be compared.",{"measure":22,"description":23,"timeFrame":24},"Event-free survival (EFS)","Event-free survival (EFS) defined as time from randomization to melanoma progression (irresectable stage III or stage IV disease), melanoma recurrence, treatment-related toxicity precluding surgery, treatment-related death, or melanoma-related death, whichever occurs first.","From date of randomization until the date of the first event as described above, assessed up to 60 months",{"measure":26,"description":27,"timeFrame":28},"Adverse Events (AE)","Percentage of Patients in Each Treatment Group with AEs, AEs with CTCAE grade ≥3","From the inclusion in the study (signature of the informed consent form - ICF) until the first follow-up visit (up to approximately 5 months).",{"measure":30,"description":31,"timeFrame":32},"Immune-related Adverse Events (irAEs)","Occurrence of immune-related Adverse Events (irAEs)","From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months).",{"measure":34,"description":35,"timeFrame":32},"Drug-Induced Liver Injury (DILI)","Number of patients with Drug-Induced Liver Injury (DILI)",{"measure":37,"description":38,"timeFrame":32},"Adverse Events of Special Interest (AESI)","Number of patients with Adverse Events of Special Interest (AESI)",{"measure":40,"description":41,"timeFrame":32},"Haematological\u002Fchemical Laboratory Abnormalities","Percentage of Subjects with Haematological\u002Fchemical Laboratory Abnormalities",{"measure":43,"description":44,"timeFrame":45},"Electrocardiogram (ECG) and echocardiogram (ECHO) abnormalities","Percentage of participants with Electrocardiogram (ECG) and echocardiogram (ECHO) abnormality findings. Data about QT\u002FQTc intervals will be collected and analysed for QT\u002FQTc prolongation potentially caused by treatment.","1) day 0-14 (screening) for both arm; 2) at week 5 (Safety assessment) only for arm 1.",{"measure":47,"description":48,"timeFrame":49},"Physical examination","Number of subjects with a clinically significant change from baseline in physical examination","From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months)",{"measure":51,"description":52,"timeFrame":49},"Concomitant medication","Number of subject with concomitant medication",{"measure":54,"description":55,"timeFrame":56},"Human anti-fusion protein antibodies (HAFA)","Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19IL2 and L19TNF","1) day 0-14 (screening) for arm 1; 2) at week 5 (Safety assessment) for Arm 1; 3) at week 12 (only first follow-up) for Arm 1.",{"measure":58,"description":59,"timeFrame":32},"Vital signs (blood pressure)","Number of subjects with a clinically significant change from baseline in vital signs (blood pressure) by visit",{"measure":61,"description":62,"timeFrame":49},"Vital signals (heart rate)","Number of subjects with a clinically significant change from baseline in vital signs (heart rate) by visit",{"measure":64,"description":65,"timeFrame":49},"Vital signals (body temperature)","Number of subjects with a clinically significant change from baseline in vital signs (body temperature) by visit",{"measure":67,"description":68,"timeFrame":69},"Pathological responses","Pathological responses (categorized into pCR, near-pCR, pPR, pNR, according to INMC criteria) assessed at time of surgical resection.","Assessed at the time of surgical resection of the tumor lesions.",[71],{"measure":72,"description":73,"timeFrame":74},"Local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS)","Local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) after randomization in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus surgery adjuvant therapy (Arm 2). LRFS is defined as survival free of loco-regional recurrence occurring at any time before systemic recurrence and other events are censored. DMFS is defined as survival free of systemic recurrence, including: 1) systemic recurrence outside the locoregional area at any time before or after locoregional relapse, 2) systemic recurrence with or without loco-regional relapse, or 3) death from cancer with no information on systemic recurrence.","From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months",{"allocation":76,"interventionModel":77,"interventionModelDescription":78,"primaryPurpose":79,"observationalModel":80,"timePerspective":80,"maskingInfo":81},"RANDOMIZED","PARALLEL","Total patients: approximately 186. Daromun plus surgery and adjuvant therapy treatment group (Arm 1): 93 evaluable patients. Surgery and adjuvant therapy (Arm 2): 93 evaluable patients. Patients enrolled will be randomized to the two different arms of the study.","TREATMENT",null,{"masking":82,"maskingDescription":80,"whoMasked":80},"NONE","The present study is an open-label, randomized, controlled, two-arm multi-center study of the efficacy of Daromun neoadjuvant intratumoral treatment followed by surgery and adjuvant therapy versus surgery and adjuvant therapy in clinical stage III B\u002FC\u002FD melanoma patients. 186 patients will be randomized in a 1:1 ratio to receive Daromun treatment followed by surgery and adjuvant therapy (Arm 1) or surgery and adjuvant therapy (Arm 2).\n\nIn both arms, follow-up for assessing recurrence-free survival will be performed up to five years after randomization. Survival information will also be collected in the following year (up to six years in total after randomization).\n\nThis is an open-label study, so there is no blinding.\n\nPatients who successfully complete the screening evaluations and are eligible for participation in the study will be enrolled and randomly assigned (1:1) to two parallel treatment arms: Daromun plus surgery and adjuvant therapy (Arm 1) or surgery and adjuvant therapy (Arm 2).\n\nTo ensure a balance across treatment groups, stratified randomization with permuted block will be used and separate randomization list for each subgroup (stratum) will be produced. Patients will be stratified on the basis of the following prognostic factors:\n\n* Stage of disease (3 levels): Stage IIIB vs. Stage IIIC vs Stage IIID\n* Planned post-surgical adjuvant therapy (2 levels): anti-PD-1 and other adjuvant therapies.\n\nThe primary objective of the study is to demonstrate that a neoadjuvant Daromun treatment followed by surgery and adjuvant therapy improves in a statistically significant manner the recurrence-free survival (RFS) of Stage IIIB\u002FC\u002FD melanoma patients with respect to the standard of care (surgery and adjuvant therapy).\n\nPrimary endpoint of the study is RFS in a time-to-event analysis in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus the surgery plus adjuvant therapy control group (Arm 2). Analysis will be based on the \"Intention To Treat\" population.\n\nThe key secondary objective of the study is to demonstrate that a neoadjuvant Daromun treatment followed by surgery and adjuvant therapy improves in a statistically significant manner the overall survival (OS) of patients with resectable Stage IIIB\u002FC\u002FD melanoma patients with respect to the standard of care (surgery and adjuvant therapy).\n\nFor patients enrolled in both arms, local approved post-surgery adjuvant therapies (as part of the standard of care) are allowed and decided at the investigator's discretion. These include high-dose interferon- α2b, anti-CTLA-4 antibodies (e.g. Ipilimumab), anti-PD1 antibodies (e.g. Nivolumab, Pembrolizumab), targeted therapies (e.g. Dabrafenib + Trametinib), or other new local approved treatments.",[85,93],{"label":86,"type":87,"description":88,"interventionNames":89},"Daromun plus Surgery and Adjuvant therapy","EXPERIMENTAL","Arm-1 patients will follow these steps:\n\n1. screening period,\n2. 4-week open-label treatment period,\n3. surgery within a maximum of 4 weeks,\n4. adjuvant therapy.",[90,91,92],"Drug: Daromun","Procedure: Surgery","Drug: Adjuvant therapy",{"label":94,"type":95,"description":96,"interventionNames":97},"Surgery and adjuvant therapy","ACTIVE_COMPARATOR","Arm-2 patients will follow these steps:\n\n1. Screening period,\n2. direct surgery within 4 weeks from randomization,\n3. adjuvant therapy.",[91,92],[99,104,109],{"type":100,"name":101,"description":102,"armGroupLabels":103,"otherNames":80},"DRUG","Daromun","Patients will receive intratumoral administrations into injectable cutaneous, subcutaneous, and nodal tumors of Daromun once weekly for up to 4 weeks.",[86],{"type":105,"name":106,"description":107,"armGroupLabels":108,"otherNames":80},"PROCEDURE","Surgery","Patients will receive surgery.",[86,94],{"type":100,"name":110,"description":111,"armGroupLabels":112,"otherNames":80},"Adjuvant therapy","Patients will receive adjuvant therapy at the investigator's discretion following the surgery.",[86,94],[114,119],{"name":115,"role":116,"phone":117,"phoneExt":80,"email":118},"Sheila Dakhel, PhD","CONTACT","+41 (0) 43 544 88 02","sheila.dakhel@philogen.com",{"name":120,"role":116,"phone":121,"phoneExt":80,"email":122},"Concetta Aulicino","+39 0577 17 816","regulatory@philogen.com",[124,143,154,163,178,193,203,213,227,242,251,259,273,288,298,311,325,339,353,367,385,399,411,423,439,455,464,476,492,507,517,531,542,555,565,575,589],{"facility":125,"status":126,"city":127,"state":128,"zip":129,"country":130,"countryCode":131,"cosmosGeoPoint":132,"geoPoint":137,"contacts":138},"Mayo Clinic Hospital","RECRUITING","Phoenix","Arizona","85054","United States","US",{"type":133,"coordinates":134},"Point",[135,136],-112.07404,33.44838,{"lat":136,"lon":135},[139,141],{"name":140,"role":116,"phone":80,"phoneExt":80,"email":80},"Mahesh Seetharam, MD",{"name":140,"role":142,"phone":80,"phoneExt":80,"email":80},"PRINCIPAL_INVESTIGATOR",{"facility":144,"status":145,"city":146,"state":147,"zip":148,"country":130,"countryCode":131,"cosmosGeoPoint":149,"geoPoint":153,"contacts":80},"UC San Diego Moores Cancer Center","ACTIVE_NOT_RECRUITING","La Jolla","California","92093",{"type":133,"coordinates":150},[151,152],-117.2742,32.84727,{"lat":152,"lon":151},{"facility":155,"status":145,"city":156,"state":147,"zip":157,"country":130,"countryCode":131,"cosmosGeoPoint":158,"geoPoint":162,"contacts":80},"UC Irvine Health-Chao Family Comprehensive Cancer Center","Orange","92868-3201",{"type":133,"coordinates":159},[160,161],-117.85311,33.78779,{"lat":161,"lon":160},{"facility":164,"status":126,"city":165,"state":166,"zip":167,"country":130,"countryCode":131,"cosmosGeoPoint":168,"geoPoint":172,"contacts":173},"Moffitt Cancer Center","Tampa","Florida","33612",{"type":133,"coordinates":169},[170,171],-82.45843,27.94752,{"lat":171,"lon":170},[174,176],{"name":175,"role":116,"phone":80,"phoneExt":80,"email":80},"Jonathan Zager",{"name":177,"role":142,"phone":80,"phoneExt":80,"email":80},"Jonathan Zager, MD",{"facility":179,"status":126,"city":180,"state":181,"zip":182,"country":130,"countryCode":131,"cosmosGeoPoint":183,"geoPoint":187,"contacts":188},"Winship Cancer Institute, Emory university","Atlanta","Georgia","30322",{"type":133,"coordinates":184},[185,186],-84.38798,33.749,{"lat":186,"lon":185},[189,191],{"name":190,"role":116,"phone":80,"phoneExt":80,"email":80},"Michael Lowe",{"name":192,"role":142,"phone":80,"phoneExt":80,"email":80},"Michael Lowe, MD",{"facility":194,"status":145,"city":195,"state":196,"zip":197,"country":130,"countryCode":131,"cosmosGeoPoint":198,"geoPoint":202,"contacts":80},"Rush University Medical Center","Chicago","Illinois","60612",{"type":133,"coordinates":199},[200,201],-87.65005,41.85003,{"lat":201,"lon":200},{"facility":204,"status":145,"city":205,"state":206,"zip":207,"country":130,"countryCode":131,"cosmosGeoPoint":208,"geoPoint":212,"contacts":80},"University of Iowa Hospitals and Clinics","Iowa City","Iowa","52242",{"type":133,"coordinates":209},[210,211],-91.53017,41.66113,{"lat":211,"lon":210},{"facility":214,"status":126,"city":215,"state":216,"zip":217,"country":130,"countryCode":131,"cosmosGeoPoint":218,"geoPoint":222,"contacts":223},"Mayo Clinic","Rochester","Minnesota","55905",{"type":133,"coordinates":219},[220,221],-92.4699,44.02163,{"lat":221,"lon":220},[224,226],{"name":225,"role":116,"phone":80,"phoneExt":80,"email":80},"Anastasios Dimou, MD",{"name":225,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":228,"status":126,"city":229,"state":230,"zip":231,"country":130,"countryCode":131,"cosmosGeoPoint":232,"geoPoint":236,"contacts":237},"Rutgers Cancer Institute, 195 Little Albany Street","New Brunswick","New Jersey","08903",{"type":133,"coordinates":233},[234,235],-74.45182,40.48622,{"lat":235,"lon":234},[238,240],{"name":239,"role":116,"phone":80,"phoneExt":80,"email":80},"Adam Berger",{"name":241,"role":142,"phone":80,"phoneExt":80,"email":80},"Adam Berger, MD",{"facility":243,"status":145,"city":244,"state":244,"zip":245,"country":130,"countryCode":131,"cosmosGeoPoint":246,"geoPoint":250,"contacts":80},"Ambulatory Care Center at NYC Langarone Health","New York","10016",{"type":133,"coordinates":247},[248,249],-74.00597,40.71427,{"lat":249,"lon":248},{"facility":252,"status":126,"city":253,"state":244,"zip":254,"country":130,"countryCode":131,"cosmosGeoPoint":80,"geoPoint":80,"contacts":255},"Memorial Sloan Kettering Cancer Center - Main Campus","Ney York","10065",[256,258],{"name":257,"role":116,"phone":80,"phoneExt":80,"email":80},"Danielle Bello",{"name":257,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":260,"status":126,"city":261,"state":262,"zip":263,"country":130,"countryCode":131,"cosmosGeoPoint":264,"geoPoint":268,"contacts":269},"Duke University Medical Center - Duke Cancer Center","Durham","North Carolina","27710",{"type":133,"coordinates":265},[266,267],-78.89862,35.99403,{"lat":267,"lon":266},[270,272],{"name":271,"role":116,"phone":80,"phoneExt":80,"email":80},"Georgia Beasley",{"name":271,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":274,"status":126,"city":275,"state":276,"zip":277,"country":130,"countryCode":131,"cosmosGeoPoint":278,"geoPoint":282,"contacts":283},"Ohio State University Wexner Medical Center","Columbus","Ohio","43210",{"type":133,"coordinates":279},[280,281],-82.99879,39.96118,{"lat":281,"lon":280},[284,286],{"name":285,"role":116,"phone":80,"phoneExt":80,"email":80},"Claire Verschraegen",{"name":287,"role":142,"phone":80,"phoneExt":80,"email":80},"Claire Verschraegen, MD",{"facility":289,"status":145,"city":290,"state":291,"zip":292,"country":130,"countryCode":131,"cosmosGeoPoint":293,"geoPoint":297,"contacts":80},"St. Luke's Cancer Center, Clinical Trial, 3rd floor, 1600 St. Luke's Blvd.","Easton","Pennsylvania","18045",{"type":133,"coordinates":294},[295,296],-75.22073,40.68843,{"lat":296,"lon":295},{"facility":299,"status":126,"city":300,"state":291,"zip":301,"country":130,"countryCode":131,"cosmosGeoPoint":302,"geoPoint":306,"contacts":307},"Penn State Cancer Institute","Hershey","17033",{"type":133,"coordinates":303},[304,305],-76.65025,40.28592,{"lat":305,"lon":304},[308,310],{"name":309,"role":116,"phone":80,"phoneExt":80,"email":80},"Joseph Drabick",{"name":309,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":312,"status":126,"city":313,"state":291,"zip":314,"country":130,"countryCode":131,"cosmosGeoPoint":315,"geoPoint":319,"contacts":320},"Fox Chase Cancer Center 333 Cottman Avenue","Philadelphia","19111",{"type":133,"coordinates":316},[317,318],-75.16362,39.95238,{"lat":318,"lon":317},[321,323],{"name":322,"role":116,"phone":80,"phoneExt":80,"email":80},"Jeffrey Farma",{"name":324,"role":142,"phone":80,"phoneExt":80,"email":80},"Jeffrey Farma, MD",{"facility":326,"status":126,"city":327,"state":328,"zip":329,"country":130,"countryCode":131,"cosmosGeoPoint":330,"geoPoint":334,"contacts":335},"The University of Texas M.D. Anderson Cancer Center","Houston","Texas","77030-4009",{"type":133,"coordinates":331},[332,333],-95.36327,29.76328,{"lat":333,"lon":332},[336,338],{"name":337,"role":116,"phone":80,"phoneExt":80,"email":80},"Hussein Tawbi",{"name":337,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":340,"status":126,"city":341,"state":342,"zip":343,"country":130,"countryCode":131,"cosmosGeoPoint":344,"geoPoint":348,"contacts":349},"Huntsman Cancer Institute, University of Utah 2000 Circle of Hope","Salt Lake City, UT","Utah","84112",{"type":133,"coordinates":345},[346,347],-111.89105,40.76078,{"lat":347,"lon":346},[350,352],{"name":351,"role":116,"phone":80,"phoneExt":80,"email":80},"John Hyngstrom",{"name":351,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":354,"status":126,"city":355,"state":356,"zip":357,"country":130,"countryCode":131,"cosmosGeoPoint":358,"geoPoint":362,"contacts":363},"VCU - McGlothlin Medical Education Center","Richmond","Virginia","980037",{"type":133,"coordinates":359},[360,361],-77.46026,37.55376,{"lat":361,"lon":360},[364,366],{"name":365,"role":116,"phone":80,"phoneExt":80,"email":80},"Andrew Poklepovic",{"name":365,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":368,"status":126,"city":369,"state":370,"zip":371,"country":372,"countryCode":373,"cosmosGeoPoint":374,"geoPoint":378,"contacts":379},"Hospital Universitari Germans Trias i Pujol","Badalona","Barcelona","08916","Spain","ES",{"type":133,"coordinates":375},[376,377],2.24741,41.45004,{"lat":377,"lon":376},[380,384],{"name":381,"role":116,"phone":382,"phoneExt":80,"email":383},"José Luis Manzano Mozo","+34615315823","jmanzano@iconcologia.net",{"name":381,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":386,"status":126,"city":370,"state":370,"zip":387,"country":372,"countryCode":373,"cosmosGeoPoint":388,"geoPoint":392,"contacts":393},"Hospital de la Santa Creu i Sant Pau","08025",{"type":133,"coordinates":389},[390,391],2.15899,41.38879,{"lat":391,"lon":390},[394,398],{"name":395,"role":116,"phone":396,"phoneExt":80,"email":397},"Margarita Majem Tarruella","+34935565638","MMajem@santpau.cat",{"name":395,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":400,"status":126,"city":370,"state":370,"zip":401,"country":372,"countryCode":373,"cosmosGeoPoint":402,"geoPoint":404,"contacts":405},"Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron","08035",{"type":133,"coordinates":403},[390,391],{"lat":391,"lon":390},[406,410],{"name":407,"role":116,"phone":408,"phoneExt":80,"email":409},"Eva Muñoz Couselo","+34932746085","emunoz@vhio.net",{"name":407,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":412,"status":126,"city":370,"state":370,"zip":413,"country":372,"countryCode":373,"cosmosGeoPoint":414,"geoPoint":416,"contacts":417},"Hospital Clinic Barcelona","08036",{"type":133,"coordinates":415},[390,391],{"lat":391,"lon":390},[418,422],{"name":419,"role":116,"phone":420,"phoneExt":80,"email":421},"Josep Malvehy Guilera","+34932275400","jmalvehy@clinic.cat",{"name":419,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":424,"status":126,"city":425,"state":426,"zip":427,"country":372,"countryCode":373,"cosmosGeoPoint":428,"geoPoint":432,"contacts":433},"El Hospital Universitario De Gran Canaria Dr. Negrin","Las Palmas de Gran Canaria","Canarie","35010",{"type":133,"coordinates":429},[430,431],-15.41573,28.10178,{"lat":431,"lon":430},[434,438],{"name":435,"role":116,"phone":436,"phoneExt":80,"email":437},"Elena Castro Gonzalez","+34928450658","elenan.castrogonzalez@gmail.com",{"name":435,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":440,"status":126,"city":441,"state":442,"zip":443,"country":372,"countryCode":373,"cosmosGeoPoint":444,"geoPoint":448,"contacts":449},"Fundacion Onkologikoa Fundazioa","Donostia \u002F San Sebastian","Gipuzkoa","20014",{"type":133,"coordinates":445},[446,447],-1.97499,43.31283,{"lat":447,"lon":446},[450,454],{"name":451,"role":116,"phone":452,"phoneExt":80,"email":453},"Karmele Mujika Eizmendi","+34943328315","kmujika@onkologikoa.org",{"name":451,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":456,"status":145,"city":457,"state":457,"zip":458,"country":372,"countryCode":373,"cosmosGeoPoint":459,"geoPoint":463,"contacts":80},"MD Anderson Cancer Center","Madrid","28033",{"type":133,"coordinates":460},[461,462],-3.70256,40.4165,{"lat":462,"lon":461},{"facility":465,"status":126,"city":457,"state":457,"zip":466,"country":372,"countryCode":373,"cosmosGeoPoint":467,"geoPoint":469,"contacts":470},"Hospital Universitario 12 de Octubre","28041",{"type":133,"coordinates":468},[461,462],{"lat":462,"lon":461},[471,475],{"name":472,"role":116,"phone":473,"phoneExt":80,"email":474},"Pedro Luis Ortiz Romero","+34913908000","pablo.ortiz@salud.madrid.org",{"name":472,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":477,"status":126,"city":478,"state":479,"zip":480,"country":372,"countryCode":373,"cosmosGeoPoint":481,"geoPoint":485,"contacts":486},"Hospital Universitario Regional de Málaga","Málaga","Malaga","29010",{"type":133,"coordinates":482},[483,484],-4.42034,36.72016,{"lat":484,"lon":483},[487,491],{"name":488,"role":116,"phone":489,"phoneExt":80,"email":490},"Elisabeth Pérez Ruiz","+34951308130","elisaonco@gmail.com",{"name":488,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":493,"status":126,"city":494,"state":494,"zip":495,"country":372,"countryCode":373,"cosmosGeoPoint":496,"geoPoint":500,"contacts":501},"Hospital Clínico Universitario Virgen de la Arrixaca","Murcia","30120",{"type":133,"coordinates":497},[498,499],-1.13004,37.98704,{"lat":499,"lon":498},[502,506],{"name":503,"role":116,"phone":504,"phoneExt":80,"email":505},"Pablo Cerezuela Fuentes","+34968369387","pcerezuelaf@seom.org",{"name":503,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":508,"status":145,"city":509,"state":510,"zip":511,"country":372,"countryCode":373,"cosmosGeoPoint":512,"geoPoint":516,"contacts":80},"Hospital Universitario Virgen De La Macarena","Seville","Sevilla","41009",{"type":133,"coordinates":513},[514,515],-5.97317,37.38283,{"lat":515,"lon":514},{"facility":518,"status":126,"city":519,"state":80,"zip":80,"country":372,"countryCode":373,"cosmosGeoPoint":520,"geoPoint":524,"contacts":525},"Hospital General Universitario de Valencia","Valencia",{"type":133,"coordinates":521},[522,523],-0.37966,39.47391,{"lat":523,"lon":522},[526,530],{"name":527,"role":116,"phone":528,"phoneExt":80,"email":529},"Alfonso Berrocal Jaime","+34963131800","berrocal.alf@gmail.com",{"name":527,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":532,"status":145,"city":533,"state":533,"zip":534,"country":535,"countryCode":536,"cosmosGeoPoint":537,"geoPoint":541,"contacts":80},"Universitätsspital Basel","Basel","4031","Switzerland","CH",{"type":133,"coordinates":538},[539,540],7.57327,47.55839,{"lat":540,"lon":539},{"facility":543,"status":126,"city":544,"state":544,"zip":545,"country":535,"countryCode":536,"cosmosGeoPoint":546,"geoPoint":550,"contacts":551},"Istituto Oncologico della Svizzera Italiana","Bellinzona","6500",{"type":133,"coordinates":547},[548,549],9.01703,46.19278,{"lat":549,"lon":548},[552,554],{"name":553,"role":116,"phone":80,"phoneExt":80,"email":80},"Cristina Mangas",{"name":553,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":556,"status":145,"city":557,"state":558,"zip":559,"country":535,"countryCode":536,"cosmosGeoPoint":560,"geoPoint":564,"contacts":80},"Insel Gruppe AG","Bern","Canton of Bern","3010",{"type":133,"coordinates":561},[562,563],7.44744,46.94809,{"lat":563,"lon":562},{"facility":566,"status":145,"city":567,"state":568,"zip":569,"country":535,"countryCode":536,"cosmosGeoPoint":570,"geoPoint":574,"contacts":80},"Hôpitaux Universitaires de Genève","Geneva","Canton of Geneva","1205",{"type":133,"coordinates":571},[572,573],6.14569,46.20222,{"lat":573,"lon":572},{"facility":576,"status":126,"city":577,"state":578,"zip":579,"country":535,"countryCode":536,"cosmosGeoPoint":580,"geoPoint":584,"contacts":585},"Kantonsspital St.Gallen","Sankt Gallen","Canton of St. Gallen","9007",{"type":133,"coordinates":581},[582,583],9.37477,47.42391,{"lat":583,"lon":582},[586,588],{"name":587,"role":116,"phone":80,"phoneExt":80,"email":80},"Nikolaus Wagner",{"name":587,"role":142,"phone":80,"phoneExt":80,"email":80},{"facility":590,"status":126,"city":591,"state":592,"zip":593,"country":535,"countryCode":536,"cosmosGeoPoint":594,"geoPoint":598,"contacts":599},"Universitätsspital Zürich (USZ)","Zurich","Canton of Zurich","8091",{"type":133,"coordinates":595},[596,597],8.55,47.36667,{"lat":597,"lon":596},[600,602],{"name":601,"role":116,"phone":80,"phoneExt":80,"email":80},"Egle Ramelyte",{"name":601,"role":142,"phone":80,"phoneExt":80,"email":80},{"type":604,"investigatorFullName":80,"investigatorTitle":80,"investigatorAffiliation":80,"oldNameTitle":80,"oldOrganization":80},"SPONSOR","100329335",false,"NCT03567889","Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB\u002FC\u002FD Melanoma Patients","An Open-Label, Randomized, Controlled Multi-Center Study of The Efficacy of Daromun (L19IL2 + L19TNF) Neoadjuvant Intratumoral Treatment Followed by Surgery and Adjuvant Therapy Versus Surgery and Adjuvant Therapy in Clinical Stage IIIB\u002FC\u002FD Melanoma Patients","NeoDREAM","Inclusion Criteria:\n\n1. Histologically or cytologically confirmed diagnosis of clinical stage IIIB, IIIC, and IIID (AJCC 8th edition) locoregional melanoma that is eligible for complete surgical resection of all metastases (surgically resectable).\n2. Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.\n3. Prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, BRAF\u002FMEK inhibitors, etc.) is allowed. Before enrollment in the study, a wash-out period of 6 weeks is required and toxicities from prior treatments should be resumed to Grade ≤1.\n4. Males or females, age ≥ 18 years.\n5. ECOG Performance Status\u002FWHO Performance Status ≤ 1.\n6. Life expectancy of \\> 24 months.\n7. Absolute neutrophil count \\> 1.5 x 109\u002FL.\n8. Hemoglobin \\> 9.0 g\u002FdL.\n9. Platelets \\> 100 x 109\u002FL.\n10. Total bilirubin ≤ 30 μmol\u002FL (or ≤ 2.0 mg\u002Fdl).\n11. ALT and AST ≤ 2.5 x the upper limit of normal (ULN).\n12. Serum creatinine \\\u003C 1.5 x ULN.\n13. LDH serum level ≤ 1.5 x ULN.\n14. Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV (i.e. positive anti-HBsAg with not vaccination and\u002For positive anti-HBcAg Ab), negative serum HBV-DNA is also required.\n15. All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1 unless otherwise specified above.\n16. All women of childbearing potential (WOCBP) must have negative pregnancy test results at the screening. WOCBP must be using, from the screening to three months following the last study drug administration, highly effective contraception methods. WOCBP and effective contraception methods are defined by the \"Recommendations for contraception and pregnancy testing in clinical trials\" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence. Pregnancy test will be repeated at the safety visit (only WOCBP and only for patients in Arm 1).\n17. Male patients with WOCBP partners must agree to use simultaneously two acceptable methods of contraception (i.e. spermicidal gel plus condom) from the screening to three months following the last study drug administration.\n18. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.\n19. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.\n\nExclusion Criteria\n\n1. Uveal melanoma or mucosal melanoma\n2. Evidence of distant metastases at screening.\n3. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except: cervical carcinoma in situ, curatively treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \\& T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry.\n4. Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.\n5. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.\n6. Inadequately controlled cardiac arrhythmias including atrial fibrillation.\n7. Heart insufficiency (\\> Grade II, New York Heart Association (NYHA) criteria).\n8. LVEF ≤ 50% and\u002For abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator.\n9. Uncontrolled hypertension.\n10. Ischemic peripheral vascular disease (Grade IIb-IV).\n11. Severe diabetic retinopathy.\n12. Active autoimmune disease.\n13. History of organ allograft or stem cell transplantation.\n14. Recovery from major trauma including surgery within 4 weeks prior to enrollment.\n15. Known history of allergy to IL2, TNF, or other human proteins\u002Fpeptides\u002Fantibodies or any other constituent of the product.\n16. Breast feeding female.\n17. Anti-tumor therapy (except small surgery) within 4 weeks before enrollment.\n18. Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before enrollment.\n19. Planned administration of growth factors or immunomodulatory agents within 7 days before enrollment.\n20. Patient requiring or taking corticosteroids or other immunosuppressant drugs on a long-term basis will be evaluated case by case with the Sponsor for inclusion\u002Fexclusion in the study. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criteria.\n21. Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.\n22. Previous enrolment and randomization in the same study.","ALL","18 Years",{"count":615,"type":616},186,"ESTIMATED","INTERVENTIONAL",[619],"PHASE3","The trial aims to evaluate the efficacy of Daromun neoadjuvant treatment followed by surgery and adjuvant therapy to improve in a statistically significant manner the recurrence-free survival (RFS) of Stage IIIB\u002FC\u002FD melanoma patients with respect to the standard of care (surgery and adjuvant therapy).",[622,623,624],"Melanoma Stage IIIB","Melanoma Stage IIIC","Melanoma Stage IIID",[622,623,624],"2025-12-15",{"date":628,"type":629},"2025-12-17","ACTUAL",{"date":631,"type":629},"2018-09-20",{"date":633,"type":616},"2031-12",{"name":5,"class":6},37]