[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100576421":3},{"organization":4,"armGroups":7,"interventions":17,"overallOfficials":36,"centralContacts":41,"locations":49,"responsibleParty":64,"collaborators":23,"id":66,"slug":67,"hasResults":68,"nctId":69,"briefTitle":70,"officialTitle":71,"acronym":23,"eligibilityCriteria":72,"healthyVolunteers":68,"sex":73,"minAge":74,"maxAge":23,"enrollmentInfo":75,"targetDuration":23,"studyType":78,"phases":79,"briefSummary":81,"conditions":82,"keywords":86,"overallStatus":51,"whyStopped":23,"lastUpdateSubmitDate":93,"lastUpdatePostDateStruct":94,"startDateStruct":97,"completionDateStruct":99,"leadSponsor":101,"locationsCount":102},{"fullName":5,"class":6},"European Institute of Oncology","OTHER",[8],{"label":9,"type":10,"description":11,"interventionNames":12},"advanced ovarian cancer patient","EXPERIMENTAL","Women with advanced ovarian cancer in complete or partial remission after surgery and eligible to oral PARP inhibitors as first line in association to chemotherapy or as maintenance therapy.",[13,14,15,16],"Procedure: buccal cells","Procedure: bone marrow cells","Procedure: peripheral blood cells","Procedure: bone marrow biopsy",[18,24,28,32],{"type":19,"name":20,"description":21,"armGroupLabels":22,"otherNames":23},"PROCEDURE","buccal cells","custom myeloid gene panel (Myelo-Panel) to identify germline mutations predisposing to cancer development (Thermo Fisher Scientific)",[9],null,{"type":19,"name":25,"description":26,"armGroupLabels":27,"otherNames":23},"bone marrow cells","Bone marrow cells (optional, for comparison, only in a limited number of patients):\n\n* morphological analysis\n* immunophenotype\n* cytogenetics\u002FFISH\n* analysis of CHIP by custom gene panel and high sensitivity NGS",[9],{"type":19,"name":29,"description":30,"armGroupLabels":31,"otherNames":23},"peripheral blood cells","analysis of CHIP by custom gene panel and high sensitivity NGS",[9],{"type":19,"name":33,"description":34,"armGroupLabels":35,"otherNames":23},"bone marrow biopsy","Bone marrow biopsy (optional, for comparison, only in a limited number of patients):\n\n* histology\n* immunohistochemistry",[9],[37],{"name":38,"affiliation":39,"role":40},"Federica Gigli","Istituto Europeo di Oncologia","PRINCIPAL_INVESTIGATOR",[42,46],{"name":38,"role":43,"phone":44,"phoneExt":23,"email":45},"CONTACT","+390257489538","federica.gigli@ieo.it",{"name":47,"role":43,"phone":44,"phoneExt":23,"email":48},"Fulvia Fusar","fulvia.fusarimperatore@ieo.it",[50],{"facility":39,"status":51,"city":52,"state":23,"zip":53,"country":54,"countryCode":55,"cosmosGeoPoint":56,"geoPoint":61,"contacts":62},"RECRUITING","Milan","20141","Italy","IT",{"type":57,"coordinates":58},"Point",[59,60],12.59836,42.78235,{"lat":60,"lon":59},[63],{"name":38,"role":43,"phone":44,"phoneExt":23,"email":45},{"type":65,"investigatorFullName":23,"investigatorTitle":23,"investigatorAffiliation":23,"oldNameTitle":23,"oldOrganization":23},"SPONSOR","100576421","genetic-landscape-in-women-with-metastatic-ovarian-cancer-before-and-during-treatment-with-parp-inhibitors-100576421",false,"NCT06785077","Genetic Landscape in Women with Metastatic Ovarian Cancer Before and During Treatment with PARP Inhibitors","Mutational Landscape of Women Suffering from Metastatic Ovarian Cancer Before Poly (ADP-ribose) Polymerase Inhibitors Maintenance Treatment and During Treatment. Incidence of Therapy-related Hematological Neoplasms.","Inclusion Criteria:\n\nWomen with advanced ovarian cancer in complete or partial remission after surgery and eligible to oral PARP inhibitors as first line in association to chemotherapy or as maintenance therapy.\n\nExclusion Criteria:\n\n* Presence of blood cell count abnormalities before PARP inhibitor treatment;\n* Bone marrow infiltration by EOC cells.","FEMALE","18 Years",{"count":76,"type":77},157,"ESTIMATED","INTERVENTIONAL",[80],"NA","Therapy related acute myeloid leukemia and myelodysplasia (t-MN) is a potential late complication of cytotoxic therapy, and it is of particular concern in the treatment of patients with epithelial ovarian carcinoma (EOC) exposed to multiple cycles of platinum-based chemotherapy during the course of their disease. An epidemiological analysis published in 2011 (Gynecologic Oncology) showed that the overall incidence of t-AML is 0.17%, with a median latency to development of leukemia of 4 years (range 0-27 years).\n\nInhibition of PARP is a potential synthetic lethal therapeutic strategy for the treatment of cancers characterized by specific DNA repair defects, such as those that harbor a BRCA1 or BRCA2 (BRCA1\u002F2) mutation and are therefore deficient in homologous recombination repair. In homologous recombination-deficient tumors, PARP inhibition eliminates an alternative DNA repair pathway essential for maintaining viability, leading to tumor cell death. The estimated prevalence of BRCA1\u002F2 mutations in V2 03\u002F06\u002F2021 2 patients with newly diagnosed high-grade serous ovarian cancer is 20-25% and it might be higher in patients with platinum-sensitive, relapsed ovarian cancer. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1\u002F2 mutations.\n\nOur hypothesis is that these patients are carriers of clonal hematopoiesis of indeterminate potential (CHIP) before treatment with PARPi. CHIP refers to the presence of clonal population(s) of hematopoietic cells with somatic mutations in genes associated with hematological malignancies (e.g. DNMT3A, ASXL1, TET2, TP53 and others), in the absence of morphological evidence of disease.\n\nThe proposed study will address the hypothesis that platinum-based chemotherapy may promote the onset of newly developed mutated clones and clonal selection of hematopoietic stem cells harboring somatic mutations.\n\nMoreover, the concomitant presence of germline mutations in cancer predisposing genes might increase the pool of pre-existing hematopoietic clones and\u002For favor the accumulation of subsequent somatic mutations.\n\nIn this context, the inhibition of PARP-mediated repair of DNA lesions created by chemo or radiotherapy can further favor t-MN development.",[83,84,85],"Leukemia, Myeloid, Acute","Myeloid Dysplasia","Ovarian Epithelial Cancer",[87,88,89,90,91,92],"PARP inhibitors (PARPi) Treatment","gene panels","clonal hematopoiesis of indeterminate potential (CHIP)","Analysis on peripheral blood","Analysis on bone marrow","Genetic analysis","2025-01-17",{"date":95,"type":96},"2025-01-20","ACTUAL",{"date":98,"type":96},"2020-10-02",{"date":100,"type":77},"2028-04-30",{"name":5,"class":6},1]