[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Gruppo Oncologico Italiano di Ricerca Clinica\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":319},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,12,0,[8,42,66,91,119,142,164,196,221,246,272,297],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":23,"conditions":24,"keywords":26,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100620871","investigation-of-recurrence-mechanisms-to-adjuvant-osimertinib-in-radically-resected-egfr-mutated-nsclc-patients-100620871",false,"NCT07363252","Investigation of REcurrence Mechanisms to Adjuvant osimertINib in Radically Resected EGFR-mutated NSCLC Patients","Investigation of REcurrence Mechanisms to Adjuvant osimertINib in Radically Resected EGFR-mutated NSCLC Patients - REMAIN Study","REMAIN","Inclusion Criteria:\n\n* Age ≥ 18 years\n* Diagnosis of radically resected IB-IIIA NSCLC with EGFR activating mutation\n* Treatment with adjuvant osimertinib (starting from September 2022, date of approval) according to clinical practice\n* Recurrence of disease during or after adjuvant therapy with osimertinib received according to clinical practice\n* Availability of tissue and\u002For liquid biopsy sample collected at the time of recurrence\n* Signed informed consent.\n\n  * Exclusion Criteria:\n* Unavailability of tissue and\u002For liquid biopsy sample collected at the time of recurrence\n* Concomitant synchronous malignancies aside from NSCLC or any concurrent and\u002For active malignancy that has required treatment within 2 years\n* Involvement in the planning and\u002For conduct of the study (applies to both investigator staff and\u002For staff at the study site).","ALL","18 Years",{"count":20,"type":21},100,"ESTIMATED","OBSERVATIONAL","Retrospective-prospective observational multicentric study including radically resected EGFR-mutated NSCLC patients relapsed during or after adjuvant osimertinib, received according to clinical practice",[25],"EGFR-mutated NSCLC",[25,27,28],"adjuvant osimertinib","Recurrence","RECRUITING","2026-04-17",{"date":32,"type":33},"2026-04-22","ACTUAL",{"date":35,"type":33},"2026-04-14",{"date":37,"type":21},"2028-12",{"name":39,"class":40},"Gruppo Oncologico Italiano di Ricerca Clinica","OTHER",25,{"id":43,"slug":44,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":48,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":50,"enrollmentInfo":51,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":53,"conditions":54,"keywords":4,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":57,"lastUpdatePostDateStruct":58,"startDateStruct":60,"completionDateStruct":62,"leadSponsor":64,"locationsCount":65},"100629807","a-prospective-observational-study-on-of-early-onset-gastrointestinal-cancer-from-tumor-features-to-patient-lifestyle-habits-100629807","NCT07479472","A Prospective Observational Study on of Early-Onset Gastrointestinal Cancer: From Tumor Features to Patient Lifestyle Habits","A Prospective Observational Study on of Early-Onset Gastrointestinal Cancer: From Tumor Features to Patient Lifestyle Habits - YOGICO Study","YOGICO","Inclusion Criteria:\n\n* Provide a signed and dated informed consent form (ICF)\n* Willing to comply with all study procedures and be available for the duration of the study\n* Male or female, aged 18-49 years old at time of EoGI cancer diagnosis\n* Patients with newly diagnosed early-onset gastrointestinal cancer histologically confirmed: colorectal, gastroesophageal and pancreatic tumor site, regardless of histological type\n* Any disease stage, performance status, and type of treatment, including experimental therapies and supportive care\n* Previous or concomitant malignancies are allowed provided they do not involve the gastrointestinal tract\n\nExclusion Criteria:\n\n* Cognitive, linguistic, or physical barriers that prevent a detailed reconstruction of the patient's personal medical history including past lifestyle habits\n* Having previously received any treatments directed at the newly diagnosed EOGI cancer (i.e., at the time of inclusion, the patient has not yet started any type of treatment, excluding surgery)","49 Years",{"count":52,"type":21},150,"The YOGICO study aims to characterize the distinctive features of EoGI cancer through a holistic approach that integrates clinical and demographic data, tumor biological characteristics, and patient lifestyle habits",[55],"Early-onset Gastrointestinal Cancer","NOT_YET_RECRUITING","2026-03-13",{"date":59,"type":33},"2026-03-18",{"date":61,"type":21},"2026-04",{"date":63,"type":21},"2028-04",{"name":39,"class":40},11,{"id":67,"slug":68,"hasResults":11,"nctId":69,"briefTitle":70,"officialTitle":71,"acronym":72,"eligibilityCriteria":73,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":74,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":76,"conditions":77,"keywords":80,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":82,"lastUpdatePostDateStruct":83,"startDateStruct":85,"completionDateStruct":87,"leadSponsor":89,"locationsCount":90},"100620355","observational-prospective-multi-centric-study-exploring-her2-mutations-incidence-and-therapeutic-management-in-ansclc-100620355","NCT07356544","Observational, Prospective, Multi-centric Study Exploring HER2 Mutations Incidence and Therapeutic Management in aNSCLC","HER2 in Advanced NSCLC: an Observational, Prospective, Multi-centric Study Exploring HER2 Mutations Incidence and Therapeutic Management in Italy. The HEROS Study - GOIRC-01-2022","HEROS","Inclusion Criteria:\n\nCohort 1 (Prevalence study population)\n\n1. Male or female, aged at least 18 years.\n2. Pathologically confirmed diagnosis of NSCLC from September 2024 to September 2025.\n3. Locally advanced (IIIC), not amenable to multimodal approach (chemo-radiotherapy), or metastatic (IV) NSCLC according to TNM VIII edition.\n4. Enrolled in ATLAS project. Cohort 2 (HER2 mutations study population)\n5. Included in Cohort 1.\n6. Presence of HER2 mutation.\n7. Enrolled in ATLAS project. Cohort 3 (Prospective Biomarker Analysis population)\n8. Included in Cohort 2.\n9. Availability of tissue sample from the first 50 patients enrolled in cohort 2.\n10. Written informed consent (HEROS project) must be obtained before any study-related procedure.\n\nExclusion Criteria:\n\n\\-",{"count":75,"type":21},50,"The HEROS study is an Italian observational multicenter prospective study aimed to investigate the current diagnostic and therapeutical approach towards HER2 mutated NSCLC in clinical practice. The enrolment will start in September 2024 until September 2025. A 12-months follow-up window will be performed.",[78,79],"NSCLC (Advanced Non-small Cell Lung Cancer)","HER2",[81],"HER2 mutated","2026-03-04",{"date":84,"type":33},"2026-03-05",{"date":86,"type":33},"2025-08-12",{"date":88,"type":21},"2027-01-31",{"name":39,"class":40},22,{"id":92,"slug":93,"hasResults":11,"nctId":94,"briefTitle":95,"officialTitle":96,"acronym":97,"eligibilityCriteria":98,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":99,"targetDuration":4,"studyType":101,"phases":102,"briefSummary":104,"conditions":105,"keywords":107,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"locationsCount":4},"100628328","phase-2-pembrolizumab-plus-lenvatinib-in-recurrent-ccrcc-patients-failing-permbrolizumab-adjuvant-treatment-100628328","NCT07460206","Pembrolizumab Plus Lenvatinib in REcurrent ccRCC Patients Failing permbroLizUmab aDjuvant trEatment","Pembrolizumab Plus Lenvatinib in REcurrent ccRCC Patients Failing permbroLizUmab aDjuvant trEatment - PRELUDE Study","PRELUDE","Inclusion Criteria:\n\n* Male or female\n* Age \\>18 years at the time of signing the informed consent\n* Histological confirmation of RCC with a clear-cell component\n* Has locally recurrent\u002Fmetastatic disease (ie, Stage IV per the American Joint Committee on Cancer)\n* Patients with RCC with sarcomatoid features are also allowed in this study\n* Participants must have progressed on treatment with Pembrolizumab administered as adjuvant treatment. Pembrolizumab treatment progression is defined by meeting all of the following criteria:\n\n  1. Has received at least 2 doses of Pembrolizumab as adjuvant treatment\n  2. Has demonstrated disease progression after adjuvant Pembrolizumab as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression (as defined in Appendix 4).\n  3. Progressive disease has been documented within 12 months from the last dose of adjuvant Pembrolizumab\n  4. Progressive disease is determined according to iRECIST. This determination is made by the investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.\n* Male partecipants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose Pembrolizumab and 30 days after last dose of Lenvatinib and agreement to refrain from donating sperm during this period.\n* Female partecipants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last, after the last dose of study treatment and agreement to refrain from donating eggs during this period.\n* Asymptomatic patients with central nervous system (CNS) metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery. Measurable disease must be present outside the CNS. Before protocol enrollment updated CNS imaging with contrast-enhanced brain CT or brain MRI is required for patients who have received CNS-focal treatment (either by surgery or by RT) ≥ 30 days from initiation of protocol treatment.\n* Evaluable International Metastatic RCC Database Consortium (IMDC) risk scores\n* Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline, unless adverse events are clinically non significant in the opinion of the investigator. Participants with endocrine related AEs who are adequately treated with hormone replacement are eligible.\n* The participant (or legally acceptable representative if applicable) provides written informed consent for the trial\n* Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (KPS \\>70). Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.\n* Have adequate organ function as defined in the following table (Table 4). Laboratory tests must be collected within 14 days prior to the start of study intervention\n* Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150\u002F90 mm Hg with no change in antihypertensive medications within 1 week prior to allocation\n* Ability to comply with protocol requirements\n* The patient or the patient's legal representative has to be able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care\n\nExclusion Criteria:\n\n* Treatment with any anti-cancer therapy as first line therapy after adjuvant therapy with pembrolizumab\n* Adjuvant treatments other than Pembrolizumab\n* Patients with non clear cell RCC\n* Symptomatic, untreated, or actively progressing CNS metastases (patient has no history of intracranial hemorrhage or spinal cord hemorrhage; patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment; no evidence of significant vasogenic edema; patient has no ongoing requirement for corticosteroids as therapy for CNS disease but anticonvulsant therapy at a stable dose is permitted; CNS metastases limited to the cerebellum or the supratentorial region, no metastases to the midbrain, pons, medulla, or spinal cord; no evidence of interim progression between completion of CNS- directed therapy and initiation of study treatment)\n* Has known leptomeningeal disease or carcinomatous meningitis\n* Uncontrolled tumor-related pain symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement; uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures).\n* Moderate to severe hepatic impairment (Child-Pugh B or C)\n* Symptomatic hypercalcemia (ionized calcium \\> 1.5 mmol\u002FL, calcium \\> 12 mg\u002FdL, or corrected calcium \\> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab\n* History of malignancy other than renal carcinoma within 5 years prior to screening, with the exception of in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer\n* Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1. Patients who are receiving single-fraction radiotherapy given for the indication of pain control are eligible\n* Active tuberculosis\n* Major surgical procedure within 3 weeks prior to initiation of study treatment. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility. Minor surgeries (e.g., tumor biopsy, placement of vascular access device) should be performed at least 10 days prior to initiation of study treatment. Patients with clinically relevant ongoing complications from prior surgery are not eligible\n* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment\n* Severe infection within 4 weeks prior to initiation of study treatment\n* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment. Administration of killed vaccines is allowed. Note: please refer to Section 5.3.2 for information on COVID-19 vaccines\n* Treatment with systemic immunostimulatory agents within 4 weeks prior to initiation of study treatment.\n* Treatment with systemic immunosuppressive medication (e.g. corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti.TNF-alfa agents) within 2 weeks prior to initiation of study treatment, with the exceptions for patients who received acute or low dose systemic immunosuppressant medication (e.g. \\>10 mg\u002Fday oral prednisone or equivalent), and patients who received corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency\n* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment\n* Prior allogeneic stem cell or solid organ transplantation\n* Any other disease that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications\n* Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority\n* Concurrent active Hepatitis B (defined as HBsAg positive and\u002For detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection or current treatment with anti-viral therapy for HBV or HCV\n* Active or history of autoimmune disease or immune deficiency (e.g. myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, vasculitis, or glomerulonephritis, multiple sclerosis, psoriatic arthritis) with the exceptions of patients with a history of autoimmune-related hypothyroidism, patients with controlled Type 1 diabetes mellitus who are on an insulin regimen, patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (are eligible provided all of following conditions are met: rash must cover \\\u003C10% of body surface area, disease is well-controlled at baseline and requires only low- potency topical corticosteroids, no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet, radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high- potency or oral corticosteroids within the previous 12 months).\n* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan\n* Malabsorption syndrome or any other condition that might affect the absorption of lenvatinib.\n* Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.\n* Uncontrolled hypertension defined as sustained blood pressure \\> 150 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment\n* Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis).\n* Stroke (including transient ischemic attack), myocardial infarction, or other symptomatic ischemic event, or thromboembolic event within 12 months before randomization, subjects with a diagnosis of incidental PE or DVT within 12 months are allowed if asymptomatic and stable at screening treated with low- molecular-weight heparins or the direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban for at least 1 week before first dose\n* Has urine protein ≥1 g\u002F24 hours. Note: Participants with proteinuria ≥2+ (≥100 mg\u002FdL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria. Note: Urine dipstick is the preferred method for testing urinary protein, however, urinalysis may be used if the use of urine dipsticks is not feasible\n* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.\n* Has a LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)\n* History of clinically significant ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities\n* History of congenital QT syndrome.\n* QT interval corrected with use of Fridericia's formula (QTcF) \\> 480 ms per ECG within 14 days before randomization\n* Significant vascular disease (e.g., aortic aneurysm or arterial dissection requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1.\n* Evidence of bleeding diathesis or significant coagulopathy.\n* Abdominal or tracheoesophageal fistula, bowel obstruction, or gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months before initiation of study treatment. Complete healing of an intra abdominal abscess must be confirmed before initiation of study treatment. Has preexisting ≥ Grade 3 gastrointestinal or non-gastrointestinal fistula\n* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)\n* Clinical signs or symptoms of GI obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding\n* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. NOTE: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage\u002Fnecrosis following lenvatinib therapy\n* Clinically significant hematuria, hematemesis, hemoptysis or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before initiation of study treatment.\n* Serious active ulcer, or untreated bone fracture\n* Prior history of hypertensive crisis or hypertensive encephalopathy\n* Known hypersensitivity to any component of the pembrolizumab formulation. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and\u002For any of its excipients. Has discontinued adjuvant Pembrolizumab due to adverse event\n* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n* Known allergy or hypersensitivity to any component of the lenvatinib formulation\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.",{"count":100,"type":21},108,"INTERVENTIONAL",[103],"PHASE2","This study is being performed as a single-arm open-label study in order to provide information on the potential benefits of the combination of pembrolizumab and lenvatinib in participants with advanced ccRCC who have progressed on Pembrolizumab as their prior therapy in the adjuvant RCC setting.",[106],"ccRCC",[108,109,110],"clear cell renal cell carcinoma","Pembrolizumab","lenvatinib","2026-03-03",{"date":113,"type":33},"2026-03-10",{"date":115,"type":21},"2026-08",{"date":117,"type":21},"2031-12",{"name":39,"class":40},{"id":120,"slug":121,"hasResults":11,"nctId":122,"briefTitle":123,"officialTitle":124,"acronym":125,"eligibilityCriteria":126,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":127,"targetDuration":4,"studyType":101,"phases":129,"briefSummary":130,"conditions":131,"keywords":133,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":135,"startDateStruct":136,"completionDateStruct":138,"leadSponsor":140,"locationsCount":141},"100628331","phase-2-maintenance-avelumab-after-second-line-platinum-based-chemotherapy-for-metastatic-urothelial-carcinoma-100628331","NCT07460245","Maintenance AVElumab After SECond Line Platinum-based Chemotherapy for Metastatic Urothelial Carcinoma","Maintenance AVElumab After SECond Line Platinum-based Chemotherapy for Metastatic Urothelial Carcinoma:AVESEC Trial - AVESEC Study","AVESEC","Inclusion Criteria:\n\n* Histologically or cytologically-confirmed diagnosis of metastatic or locally advanced unresectable urothelial carcinoma of the bladder or upper tract with predominant transitional cell carcinoma.\n* Have received first-line of therapy consisting in enfortumab vedotin plus pembrolizumab and second-line of therapy with cisplatin or carboplatin plus gemcitabine (at least 3 cycles). Adjuvant or neoadjuvant chemotherapy is allowed if completed by \\>12 months.\n* Have not progressed per RECIST v1.1 guidelines (stable disease, partial response, complete response) following completion of 3-6 cycles of second-line chemotherapy.\n* Have measurable disease by RECIST v1.1 as assessed by the investigator.\n* Estimated life expectancy of at least 3 months.\n* Willing and able to comply to study visits and procedures and be available for the duration of the study.\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1\n* Adequate organ and bone marrow function, including:\n\n  1. Absolute neutrophil count (ANC) ≥1,500\u002Fmm3 or 1.5 x 109\u002FL;\n  2. Platelets ≥100,000\u002Fmm3 or 100 x 109\u002FL;\n  3. Hemoglobin ≥9 g\u002FdL (may have been transfused);\n  4. Estimated creatinine clearance ≥30 mL\u002Fmin calculated using the Cockcroft-Gault equation;\n  5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C 2.5 x upper limit of normal (ULN);\n  6. Total bilirubin ≤1.5 x ULN. For subjects with Gilbert's disease, ≤3 mg\u002FdL.\n* Serum pregnancy test (for females of childbearing potential) negative at screening.\n* If in fertile age, must agree to use highly effective methods of contraception (licensed hormonal methods for female patients and condom for male patients) throughout the study and for at least 30 days after the last dose.\n* Male or femle ≥18 years.\n* Signed informed consent documenting that the patient has been informed on all the aspects of the study.\n* Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion\u002Fexclusion criteria.\n\nExclusion Criteria:\n\n* Patients whose disease progressed by RECIST v1.1 on second-line chemotherapy for urothelial cancer.\n* Prior grade ≥3 per National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) toxicity from an immune-checkpoint inhibitor (thyroid toxicity excluded).\n* Persisting toxicity related to prior therapy (CTCAE Grade \\> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable\n* Patients with known symptomatic central nervous system (SNC) metastases requiring steroids. Patients are eligible if treatment (radiation or surgery) for SNC metastases has been completed by at least 4 weeks before first study dose and have recovered from acute effects of treatment and are neurologically stable.\n* Has had major surgery within 4 weeks prior to first study dose. Complete wound healing must have occurred independently from the time passed.\n* Has received prior radiotherapy within 2 weeks prior to first study dose. Prior palliative radiotherapy to metastatic bone lesion(s) is permitted, provided it has been completed at least 48 hours prior to first study dose.\n* Active autoimmune disease requiring high-dose steroids or immunosuppressive treatment. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.\n* Diagnosis of any other malignancy within 5 years prior to randomization, except for radically treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6) prostate cancer on surveillance.\n* Participation in other studies involving investigational drug(s) within 4 weeks prior to randomization with the exception of observational studies.\n* Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident\u002Fstroke (\\\u003C 6 months prior to enrollment), myocardial infarction (\\\u003C 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.\n* Known prior severe hypersensitivity to study drug or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE Grade ≥3).\n* Current or prior use of immunosuppressive medication within 7 days prior to randomization, EXCEPT the following:\n\n  1. intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);\n  2. systemic corticosteroids at physiologic doses ≤ 10 mg\u002Fday of prednisone or equivalent;\n  3. steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).\n* Active and\u002For uncontrolled infection. The following exceptions apply:\n\n  1. Participants with HIV infection are eligible if they are on effective antiretroviral therapy with undetectable viral load within 6 months, provided there is no expected drug-drug interaction.\n  2. Participants with evidence of chronic HBV infection are eligible if the HBV viral load is undetectable on suppressive therapy (if indicated), and if they have ALT, AST, and total bilirubin levels \\\u003C ULN, and provided there is no expected drug-drug interaction.\n  3. Participants with a history of HCV infection are eligible if they have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load, and if they have ALT, AST, and total bilirubin levels \\\u003C ULN.\n* Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.\n* Prior organ transplantation including allogenic stem-cell transplantation;\n* Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivate vaccines (eg, inactivated influenza vaccines).\n* Pregnant or lactating female patients; male patients able to father children, and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception for the duration of the study and for at least 60 days after the last dose of study drug.",{"count":128,"type":21},144,[103],"This study represents an innovative opportunity in the treatment of metastatic urothelial carcinoma",[132],"Urothelial Carcinoma",[134],"Avelumab",{"date":113,"type":33},{"date":137,"type":21},"2026-06",{"date":139,"type":21},"2030-12",{"name":39,"class":40},19,{"id":143,"slug":144,"hasResults":11,"nctId":145,"briefTitle":146,"officialTitle":147,"acronym":148,"eligibilityCriteria":149,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":150,"targetDuration":4,"studyType":101,"phases":151,"briefSummary":152,"conditions":153,"keywords":4,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":156,"startDateStruct":158,"completionDateStruct":160,"leadSponsor":162,"locationsCount":163},"100625153","phase-2-a-multicenter-open-label-phase-ii-study-of-cemiplimab-plus-chemotherapy-selected-on-the-basis-of-baseline-cytidine-deaminase-activity-in-advanced-squamous-non-small-cell-lung-cancer-100625153","NCT07418931","A Multicenter Open-label Phase II Study of Cemiplimab Plus Chemotherapy, Selected on the Basis of Baseline Cytidine Deaminase Activity, in Advanced Squamous Non-small Cell Lung Cancer","A Multicenter Open-label Phase II Study of Cemiplimab Plus Chemotherapy, Selected on the Basis of Baseline Cytidine Deaminase Activity, in Advanced Squamous Non-small Cell Lung Cancer - CECYDE Study","CECYDE","Inclusion Criteria:\n\n* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n* Written informed consent and any locally required authorization obtained from the patient\u002Flegal representative prior to performing any protocol-related procedures, including screening evaluations.\n* Age \\> 18 years at the time of study entry.\n* Histologically or cytologically (cell blocks only; smears are not acceptable) documented pulmonary squamous carcinoma.\n* Stage IV or recurrent disease according to the AJCC 8th edition Cancer Staging Manual.\n* Body weight \\> 30 kg\n* No prior chemotherapy or treatment with another systemic anti-cancer agent for the metastatic disease.\n* Patients who have received prior neo-adjuvant, adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment- free interval of at least 6 months from enrolment since the last chemotherapy or completion of chemoradiotherapy.\n* Patients who received prior anti-PD-(L)1 as adjuvant or neoadjuvant therapy at stage 3B \u002F3C disease will be allowed if have experienced a treatment-free interval of at least 6 months from enrolment since the last immunotherapy dose.\n* Known PD-L1 tumor status as determined by an IHC assay performed by local laboratory on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening.\n* No need for concomitant chest irradiation.\n* ECOG perforance status 0-1.\n* Life expectancy ≥12 weeks.\n* At least one lesion measurable according to RECIST v 1.1 outside of the CNS, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis \\> 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.\n* Adequate hematologic function as evidenced by absolute neutrophil count (ANC) ≥1,500\u002FμL, hemoglobin ≥ 9.0 g\u002FdL (5.58 mmol\u002FL), and platelet count ≥ 100,000\u002Fμl.\n* Adequate hepatic and renal function:\n\n  * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN).\n  * ALT (SGPT), AST (SGOT) ≤ 2.5 x institutional upper limit of normal (\\\u003C 5 x ULN if the liver has tumor involvment).\n  * Serum creatinine ≤ 1.5 times the ULN or creatinine clearance ≥ 60 mL\u002Fmin, calculated according to the standard Cockcroft and Gault formula.\n* The patient has adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) (PTT\u002FaPTT) \\\u003C 1.5 x ULN.\n* Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤ 3.0.\n* Female patients must have a negative pregnancy test and not be breast feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:\n\n  * Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.\n  * Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments and with LH and FSH levels in the post- menopausal range for the institution.\n  * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation\n  * For female patients of childbearing potential, agreement (by patient and\u002For partner) to use a highly effective form of contraception that results in a low failure rate (\\\u003C 1% per year) when used consistently and correctly, and to continue its use for 6 months after the last dose of chemotherapy or at least 4 months after the last dose of cemiplimab, whichever occurs last. Such methods include: combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, and vasectomized partner (on the understanding that this is the only one partner during the whole study duration).\n* Male patients who are sexually active must be willing to use barrier contraceptives (i.e.; by use of condoms) during sex with all partners during treatment with chemotherapy and for at least 6 months after the last dose of chemotherapy or at least 4 months after the last dose of cemiplimab, whichever occurs last. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing study treatment.\n* Ability to comply with the study protocol, in the investigator's judgment.\n\nExclusion Criteria:\n\n* Patients with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene, or with anaplastic lymphoma kinase (EML4-ALK) translocations or with ROS1 proto-oncogene receptor tyrosine kinase (ROS1) translocations. EGFR mutations, ALK and ROS1 translocations will be assessed in never- smoker patients\n* Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is required within 4 weeks prior to registration) requiring immediate radiotherapy for palliation. Patients with asymptomatic CNS lesions are eligible, provided that all of the following criteria are met:\n\n  1. The patient has no history of intracranial haemorrhage, spinal cord haemorrhage or haemorrhagic intracranial lesions\n  2. At least 14 days between the end of stereotactic radiotherapy or whole brain radiotherapy and initiation of study treatment, or at least 28 days between neurosurgical resection and initiation of study treatment\n  3. The patient is on a dose of corticosteroids ≤ 10 mg of oral prednisone or equivalent; anticonvulsant therapy at a stable dose is permitted\n  4. Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla or spinal cord)\n  5. There is no evidence of interim progression between completion of CNS directed therapy (if administered) and initiation of study treatment.\n* History of leptomeningeal disease.\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Patients with indwelling catheters (e.g., Pleura-Cath) are allowed.\n* Uncontrolled or symptomatic hypercalcemia (ionized calcium \\> 1.5 mmol\u002FL, calcium \\> 12 mg\u002FdL or corrected calcium \\> ULN).\n* History of cardiac disease: congestive heart failure \\>NYHA class 2; active CAD (MI or acute coronary syndrome more than 12 months prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.\n* Transient ischemic attack or stroke within 1 year\n* Active SARS- COV-2 infection.\n* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C.\n* Participants with HBsAg positive who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are eligible. Participants with controlled infections must undergo periodic monitoring of HBV DNA. Participants must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study medication.\n* Participants with HBsAg negative but total HBcAb positive are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, initiate HBV antiviral therapy before study entry. If serum HBV DNA PCR is below the limit of detection, periodic monitoring of HBsAg must be performed.\n* Participants who are HCV Ab+ who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are eligible.\n* Known positive serology for HIV. Participants with known controlled HIV infection (undetectable viral load on HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are eligible. For these participants monitoring will be performed per local standards.\n* Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication\n* Significant traumatic injury or radiotherapy involving an extensive field within the last 4 weeks prior to first dose of study treatment or anticipation of the need for major surgery during study treatment. Palliative radiotherapy to a limited field is allowed if concluded at least 2 weeks prior enrolment.\n* Other malignancies (previous or current), except for adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, localized prostate cancer surgically treated with curative intent or ductal carcinoma in situ treated surgically treated with curative intent or if previous malignancy was more than 5 years prior and there are no signs or symptoms of recurrence.\n* Major surgery (including open biopsy) within 28 days prior to first dose of protocol therapy.\n* Prior allogeneic stem cell or solid organ transplantation.\n* Patients with any underlying medical condition that might be aggravated by treatment or which cannot be controlled i.e. patients with active serious infection, uncontrolled diabetes mellitus, pericardial effusion.\n* Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment other than those in the present study. Concurrent use of hormonal therapy for non-cancer- related conditions (e.g., hormone replacement therapy) is acceptable.\n* Treatment with any other investigational agent within 30 days prior to starting study treatment, or concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.\n* Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra- indicates the use of an investigational drug or puts the patient at high risk for treatment- related complications\n* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \\[e.g., colitis or Crohn's disease\\], diverticulitis \\[with the exception of diverticulosis\\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\\]). The following are exceptions to this criterion:\n\n  1. Patients with vitiligo or alopecia\n  2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement\n  3. Any chronic skin condition that does not require systemic therapy. Patients without active disease in the last 5 years may be included but only after consultation with the study physician\n  4. psoriasis that does not require systemic treatment.\n  5. Patients with celiac disease controlled by diet alone.\n* History or active autoimmune neurologic paraneoplastic syndrome (e.g. non infectious encephalitis, Lambert- Eaton syndrome etc.) or any other immune-mediated paraneoplastic syndrome.\n\nPatients with SIADH or ectopic ATCH production are allowed on the study.\n\n* Patient has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication\n* History of idiopathic pulmonary fibrosis, including pneumonitis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.\n* Prior therapy for metastatic disease with any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent and anti-CTL-A4 agent.\n* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \\[IL-2\\]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment.\n* Any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization. The following are exceptions to this criterion:\n\n  1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)\n  2. Systemic corticosteroids at physiologic doses not to exceed 10 mg\u002Fday of prednisone or its equivalent\n  3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).\n* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.\n* History of allergies or hypersensitivity to any study drugs or study drug components or excipient.\n* Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:\n\n  1. Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.\n  2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with carboplatin, paclitaxel, gemcitabine or cemiplimab may be included only after consultation with the Study Physician.\n* Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.\n\n  * Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 6 months after last chemotherapy dose or at least 4 months after the last dose of cemiplimab, whichever occurs last. WOCBP and men who are unwilling to practice highly effective contraception prior to the initial dose\u002Fstart of the first treatment, during the study, and for at least 4 months after the last dose. Highly effective contraceptive measures include:\n  * Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening;\n  * Intrauterine device; intrauterine hormone-releasing system;\n  * Bilateral tubal occlusion\u002Fligation;\n  * Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure); and\u002For Sexual abstinence\n* Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing study treatment.\n* Patients should not donate blood whilst on this study.",{"count":100,"type":21},[103],"This is a multicenter phase II study enrolling treatment- naïve patients with metastatic or recurrent squamous carcinoma of the lung",[154],"Advanced Squamous Non-Small Cell Lung Cancer","2026-02-11",{"date":157,"type":33},"2026-02-18",{"date":159,"type":21},"2026-05",{"date":161,"type":21},"2030-11",{"name":39,"class":40},15,{"id":165,"slug":166,"hasResults":11,"nctId":167,"briefTitle":168,"officialTitle":169,"acronym":170,"eligibilityCriteria":171,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":172,"targetDuration":4,"studyType":101,"phases":174,"briefSummary":175,"conditions":176,"keywords":178,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":187,"lastUpdatePostDateStruct":188,"startDateStruct":190,"completionDateStruct":192,"leadSponsor":194,"locationsCount":195},"100622296","phase-2-xelox-plus-dostarlimab-versus-xelox-alone-as-consolidation-treatment-after-standard-chemoradiation-in-pmmrmss-or-msi-low-locally-advanced-rectal-cancer-larc-patients-100622296","NCT07381777","XELOX Plus DoSTARlimab Versus XELOX Alone as Consolidation Treatment After Standard Chemoradiation in pMMR\u002FMSS or MSI-Low Locally Advanced Rectal Cancer (LARC) Patients","Phase II Randomized Trial of XELOX Plus DoSTARlimab Versus XELOX Alone as Consolidation Treatment After Standard Chemoradiation in pMMR\u002FMSS or MSI-Low Locally Advanced Rectal Cancer (LARC) Patients - IMMUNOSTAR Trial GOIRC-02-2024","IMMUNOSTAR","Inclusion Criteria:\n\n* Histologically proven rectal adenocarcinoma with distal extension less 16 cm from the anal verge.\n* Stage cT3-4 cN0 cM0, any cT cN+ M0 \\[N+ stage, three or more lymph nodes of diameter \\>0.5 cm measured by endorectal ultrasound, or one or more lymph nodes of diameter \\>1 cm measured by magnetic resonance (MRI)\\].\n* Proficient mismatch repair (pMMR)\u002Fmicrosatellite stable status (MSS) or microsatellite instability (MSI)-low (MSI-L)\n* ECOG-Performance Status 0-1\n* No previous treatment with chemotherapy or radiation therapy.\n* No prior exposure to immune-mediated therapy, excluding therapeutic anticancer vaccines.\n* Neutrophil count \\>1,500\u002FmL, platelet count \\>100.000\u002FmL, hemoglobin \\>9.0 g\u002FdL, serum creatinine \\\u003C1.5 3 upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase 2.5 3 ULN, total bilirubin \\\u003C1.5 3 ULN.\n* Signed written informed consent.\n\nExclusion Criteria:\n\n* Subjects with active, known, or suspected autoimmune disease requiring systemic treatment (systemic steroids or immunosuppressive agents), except for subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune conditions only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.\n* Distant metastases documented.\n* Participants have received a live vaccine within 30 days of the planned start of study therapy. COVID-19 vaccines that do not contain live viruses are allowed. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live.\n* Participants have a current active history of pneumonitis or interstitial lung disease.",{"count":173,"type":21},270,[103],"This is a phase II, multicenter, randomized (2:1) controlled, clinical trial to evaluate the preliminary efficacy and safety of consolidation chemotherapy (XELOX) plus dostarlimab after standard long-course CRT (ARM A) compared to XELOX alone (ARM B) in patients with pMMR\u002FMSS or MSI-Low LARC (cT3-4 cN0, any cT cN+) candidate to receive standard long course CRT followed by TME. After the surgery, the patients in ARM A will be randomized (1:1) to receive adjuvant dostarlimab (ARM A1) versus follow-up (ARM A2), and in ARM B only follow-up.\n\nIf clinical complete responses (cCR) are documented after consolidation treatment, the patient may choose not to proceed with surgery and pursue nonoperative management (NOM).",[177],"Locally Advanced Rectal Cancer (LARC)",[179,180,181,182,183,184,185,186],"Consolidation chemotherapy","dostarlimab","pMMR\u002FMSS","MSI-Low","LARC","phase II","clinical complete response (cCR)","safety","2026-01-26",{"date":189,"type":33},"2026-02-02",{"date":191,"type":21},"2026-01-31",{"date":193,"type":21},"2030-12-31",{"name":39,"class":40},30,{"id":197,"slug":198,"hasResults":11,"nctId":199,"briefTitle":200,"officialTitle":201,"acronym":202,"eligibilityCriteria":203,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":204,"targetDuration":4,"studyType":101,"phases":206,"briefSummary":207,"conditions":208,"keywords":210,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":213,"lastUpdatePostDateStruct":214,"startDateStruct":216,"completionDateStruct":218,"leadSponsor":220,"locationsCount":41},"100567047","phase-2-atezolizumab-and-rechallenge-chemotherapy-in-relapsed-patients-with-extensive-stage-small-cell-lung-cancer-es-sclc-100567047","NCT06663098","Atezolizumab and Rechallenge Chemotherapy in Relapsed Patients With Extensive-stage Small Cell Lung Cancer (ES-SCLC).","Continued PD-L1 Inhibition With Atezolizumab With Rechallenge Chemotherapy in Patients With Sensitive Relapse SCLC Progressing on First-line Platinum-etoposide Chemotherapy and a PD-L1 Inhibitor: CARRY-ON Study-GOIRC-01-2023","CARRY-ON","Inclusion Criteria:\n\n1. Diagnosis of small-cell lung cancer (SCLC) (according to WHO classification 2015) confirmed at pathology (histology or cytology).\n2. Male or female and ≥ 18 years of age.\n3. Life expectancy ≥ 12 weeks.\n4. Disease progression at least 60 days after the completion of first-line chemotherapy consisting of at least 4 cycles of platinum-etoposide plus either atezolizumab or durvalumab and have not received any other treatment (except for immunotherapy as maintenance treatment); the 60 day-interval is calculated from the date of the last chemotherapy administration to the date of the first radiologically documented progressive disease.\n5. No previous radiotherapy on the only one site disease progression, unless that site had subsequent evidence of progressive disease.\n6. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2.\n7. Patients with treated brain metastases (or untreated but asymptomatic) and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also eligible. Radiotherapy must have been completed a minimum of 14 days prior to registration, and patients must have recovered from AEs related to radiotherapy to \\\u003C grade 1 (except alopecia)\n8. For Females: must be postmenopausal (defined as occurring 12 months after last menstrual period) before the screening visit, or are surgically sterile. If they are of childbearing potential, a negative serum pregnancy test prior to study entry has to be documented; furthermore, they agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 5 months after the last dose of study drug,or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject.\n9. For Males: even if surgically sterilized (i.e., post-vasectomy status) agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject.\n10. Normal baseline laboratory values as specified below:\n\n    * Absolute neutrophil count (ANC) ≥1500\u002Fmm3\n    * Platelet count ≥ 100 x 109\u002FL (≥100,000\u002FμL) without transfusion\n    * Hemoglobin ≥ 90 g\u002FL (≥ 9 g\u002FdL); patients may be transfused to meet this criterion.\n    * Total bilirubin \\\u003C 1.5x the institutional upper limit of normal (ULN)\n    * Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \\\u003C 2.5x the institutional ULN (\\\u003C 5x if liver function test elevations are due to liver metastases)\n    * Creatinine \\\u003C 1.5x institutional ULN or estimated creatinine clearance using the Cockcroft-Gault formula ≥ 30 mL\u002Fminute for patients with creatinine levels above institutional limits\n    * For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 x ULN\n    * Negative HIV test at screening {with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200\u002FμL, and have an undetectable viral load}\n    * Negative hepatitis B surface antigen (HBsAg) test at screening\n    * Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following:\n\n      * Negative total hepatitis B core antibody (HBcAb)\n      * Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA testNegative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test must be performed for patients who have a positive HCV antibody test.\n11. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion\u002Fexclusion criteria.\n12. Recovered (i.e., ≤ grade 1 toxicity) from effects of prior anticancer therapy, except alopecia.\n13. Prior radiotherapy is allowed provided that it has been completed more than 2 weeks before starting protocol treatment and patients have recovered from AEs related to radiotherapy to \\\u003C grade 1\n14. Ability to comply with protocol requirements.\n15. The patient or the patient's legal representative has to be able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.\n\nExclusion Criteria:\n\n1. More than 1 line of prior treatment for ES-SCLC.\n2. First-line treatment without either atezolizumab or durvalumab.\n3. First-line chemotherapy other than platinum-etoposide.\n4. Less than 4 cycles of first-line platinum-etoposide.\n5. Presence of resistant relapse (progressive disease within 60 days from the end of first-line chemotherapy) or refractory disease (progressive disease during the first 4 cycles of first-line chemoimmunotherapy).\n6. Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is required within 4 weeks prior to randomization)requiring immediate radiotherapy for palliation. Patients with treated brain metastases (or untreated but asymptomatic) and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also eligible provided that all of the following criteria are met:\n\n   * If treated, at least 14 days between the end of stereotactic radiotherapy or whole brain radiotherapy and initiation of study treatment and recovery from AEs related to radiotherapy to ≤ grade 1 (except alopecia), or at least 28 days between neurosurgical resection and initiation of study treatment;\n   * Anticonvulsant therapy at a stable dose is permitted;\n   * Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla or spinal cord);\n   * There is no evidence of interim intracranial progression between completion of CNS directed therapy (if administered) and initiation of study treatment.\n7. Evidence of leptomeningeal disease.\n8. Any comorbid condition or unresolved toxicity that would preclude administration of second-line chemotherapy.\n9. Patient has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines and COVID vaccines that do not contain live virus are permitted. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.\n10. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \\[IL-2\\]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment except for PD-L1 inhibitor maintenance as part of first-line treatment.\n11. Any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of registration . The following are exceptions to this criterion:\n\n    * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection);\n    * Systemic corticosteroids at physiologic doses not to exceed 10 mg\u002Fday of prednisone or its equivalent;\n    * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).\n12. Diagnosed with or treated for another malignancy within 3 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present.\n13. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment other than those in the present study. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.\n14. Treatment with any other investigational agent within 30 days prior to starting study treatment, or concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.\n15. Infection requiring intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug.\n16. Prior allogeneic stem cell or solid organ transplantation.\n17. For female subjects: positive serum pregnancy test, pregnancy, or breastfeeding.\n18. Surgery within 4 weeks (or 2 weeks for a minor surgery) before study enrolment and not fully recovered to baseline or to a stable clinical status. Insertion of a vascular device is allowed.\n19. Patients who experienced medically significant or NCI CTCAE Grade 3 or higher toxicities in response to first-line immunotherapy\n20. Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel.",{"count":205,"type":21},142,[103],"The goal of this clinical trial is to learn if a combination of atezolizumab and standard chemotherapy works to treat sensitive Extensive-stage Small Cell Lung Cancer, progressing after first-line of treatment.\n\nThe main questions it aims to answer are:\n\n* Does combination of atezolizumab and standard chemotherapy increase overall survival?\n* What medical problems do participants have when taking combination of atezolizumab and standard chemotherapy?\n\nParticipants will:\n\n* take atezolizumab and standard chemotherapy every 3 weeks for 4 cycles and than atezolizumab every 3 weeks up to 18 cycles.\n* visit the clinic once every 3 weeks for checkups and tests\n* perform Radiological assessments after 6 weeks and then every 12 weeks to determine response to treatment.",[209],"Extensive Stage Small Cell Lung Cancer (ES-SCLC)",[211,212],"Extensive-stage small cell lung cancer","atezolizumab","2025-03-11",{"date":215,"type":33},"2025-03-13",{"date":217,"type":33},"2025-01-24",{"date":219,"type":21},"2029-06-01",{"name":39,"class":40},{"id":222,"slug":223,"hasResults":11,"nctId":224,"briefTitle":225,"officialTitle":226,"acronym":227,"eligibilityCriteria":228,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":229,"targetDuration":4,"studyType":101,"phases":231,"briefSummary":233,"conditions":234,"keywords":236,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":213,"lastUpdatePostDateStruct":240,"startDateStruct":241,"completionDateStruct":243,"leadSponsor":245,"locationsCount":141},"100438955","phase-3-atezolizumab-versus-placebo-for-the-adjuvant-treatment-of-malignant-pleural-mesothelioma-atezomeso-100438955","NCT04996017","Atezolizumab Versus Placebo for the Adjuvant Treatment of Malignant Pleural Mesothelioma (Atezomeso)","PHASE III STUDY WITH ATEZOLIZUMAB VERSUS PLACEBO IN MALIGNANT PLEURAL MESOTHELIOMA PATIENTS AFTER PLEURECTOMY\u002FDECORTICATION","AtezoMeso","Inclusion Criteria\n\n* Signed informed Consent Form\n* Age ≥ 18 years on day of signing informed consent\n* Histologically confirmed malignant pleural mesothelioma\n* Surgical resection (P\u002FD), without macroscopic residual. For stage I patient without visceral involvement a total pleurectomy is allowed\n* Absence of measurable or non-measurable disease assessed with CT scan after surgery\n* Patients must have received at least no 4 cycles of platinum\u002Fpemetrexed\n* perioperative chemotherapy as per local practice (neoadjuvant or adjuvant or both). Less than 4 cycles of chemotherapy are allowed for clinical decisions\n\n  \\- In patients previously treated with neoadjuvant chemotherapy, randomization\n* should occur within 50 days from surgical resection.\n\n  \\- In patients treated with adjuvant chemotherapy, randomization should occur\n* within 30 ±7 days from last dose of adjuvant treatment.\n* Performance status of 0-1 on the ECOG Performance Scale\n* Availability of a representative tumor specimen for exploratory biomarker research (see Section 4.5.6 for information on tumor specimens) A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report prior to study enrollment.\n* Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: ANC ³ 1.5 ´ 109\u002FL (1500\u002FmL) without granulocyte colony-stimulating factor support Lymphocyte count ³ 0.5 ´ 109\u002FL (500\u002FmL) Platelet count ³ 100 ´ 109\u002FL (100,000\u002FmL) without transfusion Hemoglobin 9 g\u002FdL Patients may be transfused to meet this criterion. AST, ALT, and alkaline phosphatase (ALP) £ 2.5 ´ upper limit of normal (ULN)\n\nBilirubin £ 1.5 ´ ULN with the following exception:\n\nPatients with known Gilbert disease: bilirubin level £ 3 ´ ULN. Creatinine £ 1.5 ´ ULN Albumin ³ 25 g\u002FL (2.5 g\u002FdL) For patients not receiving therapeutic anticoagulation: INR or aPTT £ 1.5 ´ ULN\n\n• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of \\\u003C 1% per year during the treatment period and for 5 months after the final dose of atezolizumab. Women must refrain from donating eggs during this same period.\n\nA woman is considered to be of childbearing potential if she is postmenarcheal, hasnot reached a postmenopausal state (³12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and\u002For uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Examples of contraceptive methods with a failure rate of \\\u003C1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.\n\nThe reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) andn withdrawal are not acceptable methods of contraception. If required per local guidelines or regulations, locally recognized acceptable methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.\n\nWomen with a positive pregnancy test at enrollment or prior to administration of study medication will be excluded.\n\nExclusion Criteria\n\n* Patient with macroscopic residual disease after surgery, evaluated with CT scan\n* after surgery or adjuvant therapy\n* Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll\n* Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy\n* Active infection requiring systemic therapy\n* Patient with positive result to Human Immunodeficiency Virus (HIV) (HIV 1\u002F2\n* antibodies) test\n* Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \\[qualitative\\] is detected) 7. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis\n* obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of\n* active pneumonitis on screening chest computed tomography (CT) scan. NOTE:\n* History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Known active tuberculosis\n* Significant cardiovascular disease (such as New York Heart Association Class II or\n* greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable\n* angina\n* Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of\n* study treatment, or anticipation of need for a major surgical procedure during the\n* study\n* Severe infection within 4 weeks prior to initiation of study treatment, including, but\n* not limited to, hospitalization for complications of infection, bacteremia, or severe\n* pneumonia\n* Prior allogeneic stem cell or solid organ transplantation\n* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications\n* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab15. Current treatment with anti-viral therapy for HBV\n* Treatment with investigational therapy within 28 days prior to initiation of study\n* treatment\n* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies\n* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \\[IL-2\\]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment\n* Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:\n\n  * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Scientific Responsible approval has been obtained\n  * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study\n* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation\n* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment\n* Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.",{"count":230,"type":21},162,[232],"PHASE3","This is a multicentric double-blind, placebo controlled, phase III trial. In this study, patients who underwent to a surgical resection of pleural mesothelioma and are without signs of macroscopic residual disease will be randomized 2:1 to receive atezolizumab or placebo. Patients will be treated for 12 months or until recurrence, unacceptable toxicity or patient\u002Fphysician decision, whichever occurs first.\n\nRandomization will be done via a centralized system and patients will be stratified histology (epithelioid vs non epithelioid) and stage (I vs\n\n\\>I). Patients will be radiologically evaluated after surgical procedure before starting therapy and then every 12 weeks for 24 months or until disease progression. At screening patients should be without macroscopic residual disease. Quality of life questionnaire will be administered to patient at baseline and every 12 weeks. During the study baseline tumor blocks will be centrally analyzed to determinate biological characteristics and gene expression.",[235],"Mesotheliomas Pleural",[237,238,239],"mesothelioma","Adjuvant therapy","immunotherapy",{"date":215,"type":33},{"date":242,"type":33},"2021-12-14",{"date":244,"type":21},"2029-06-30",{"name":39,"class":40},{"id":247,"slug":248,"hasResults":11,"nctId":249,"briefTitle":250,"officialTitle":251,"acronym":252,"eligibilityCriteria":253,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":254,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":256,"conditions":257,"keywords":259,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":263,"lastUpdatePostDateStruct":264,"startDateStruct":266,"completionDateStruct":268,"leadSponsor":270,"locationsCount":271},"100558265","retrospective-analysis-of-patients-with-metastatic-renal-cell-carcinoma-treated-with-cabozantinib-100558265","NCT06548867","Retrospective Analysis of Patients With Metastatic Renal Cell Carcinoma Treated With CABOzantinib","Retrospective Analysis of Patients With Metastatic Renal Cell Carcinoma Treated With CABOzantinib: a GENomic Signature for Describing Long-lasting Response","CABOGEN","Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Patients with histological diagnosis of predominantly clear cell carcinoma\n* Availability of the tumor tissue from the primary tumor and\u002For a metastatic site for the genomic profiling analysis not older than 5 years.\n* Evaluable disease according to RECIST criteria v 1.1\n* Treatment with cabozantinib after one or more previous therapies for mRCC\n* Patient progressed from the start to cabozantinib therapy within 3 months or after 9 months\n* Any prognosis group according to the IMDC risk score\n* Signed informed consent must be obtained for living patients. Patients who died and patient untraceable will be analyzed based on the Authorization no. 9\u002F2016 of the Italian Data Protector Supervisor.\n\nExclusion Criteria:\n\n* Non-availability of tumor tissue from the primary tumor or a metastatic site for biomarker analysis\n* Patient progressed between 3 and 9 months from the beginning of treatment with cabozantinib.\n* Non-availability of clinical information useful to evaluate the IMDC risk group at baseline.",{"count":255,"type":21},80,"CABOGEN is a Observational, retrospective, multicenter study that will enroll patients with metastatic clear cell renal carcinoma (mccRCC) treated with cabozantinib after one or more previous lines of treatment that included TKIs, immune checkpoint inhibitors or mTOR inhibitors.",[258],"Metastatic Renal Cell Carcinoma",[258,260,261,262],"Genomic signature","long lasting response","cabozantinib treatment","2024-08-08",{"date":265,"type":33},"2024-08-12",{"date":267,"type":33},"2024-05-28",{"date":269,"type":21},"2025-06-30",{"name":39,"class":40},1,{"id":273,"slug":274,"hasResults":11,"nctId":275,"briefTitle":276,"officialTitle":277,"acronym":278,"eligibilityCriteria":279,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":280,"targetDuration":4,"studyType":101,"phases":282,"briefSummary":283,"conditions":284,"keywords":286,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":289,"lastUpdatePostDateStruct":290,"startDateStruct":292,"completionDateStruct":294,"leadSponsor":296,"locationsCount":271},"100551744","phase-2-agnostic-therapy-in-a-phase-ii-single-arm-study-in-first-line-treatment-of-durvalumab-in-association-with-carboplatin-or-cisplatin-and-etoposide-in-patients-affected-by-extensive-stage---extrapulmonary-small-cell-carcinoma-100551744","NCT06464068","AGNOSTIC THERAPY IN A PHASE II SINGLE-ARM STUDY IN FIRST-LINE TREATMENT OF DURVALUMAB IN ASSOCIATION WITH CARBOPLATIN OR CISPLATIN AND ETOPOSIDE IN PATIENTS AFFECTED BY EXTENSIVE STAGE - EXTRAPULMONARY SMALL CELL CARCINOMA","AGNOSTIC THERAPY IN A PHASE II, MULTICENTER, SINGLE-ARM STUDY IN FIRST-LINE TREATMENT OF DURVALUMAB IN ASSOCIATION WITH CARBOPLATIN OR CISPLATIN AND ETOPOSIDE IN PATIENTS AFFECTED BY EXTENSIVE STAGE - EXTRAPULMONARY SMALL CELL CARCINOMA","DURVASCC","Inclusion Criteria:\n\n* 1\\. Age ≥ 18 years on day of signing informed consent. 2. Written informed consent and any locally required authorization obtained from the patient\u002Flegal representative prior to performing any protocol-related procedures, including screening evaluations.\n\n  3\\. Histologically or cytologically confirmed extensive disease extrapulmonary small cell carcinoma.\n\n  4\\. Brain metastases; must be asymptomatic or treated and stable off steroids and anti-convulsant for at least 1 month prior to study treatment. Patients with suspected brain metastases at screening should have a CT\u002FMRI of the brain prior to study entry. 5. No prior exposure to immune-mediated therapy, including durvalumab excluding therapeutic anticancer vaccines. 6. No prior exposure to chemotherapy for advance disease. 7. Performance status of 0 or 1 on the ECOG Performance Scale. 8. Life expectancy ≥12 weeks at enrollment (day 1). 9. Patients must be considered suitable to receive a platinum-based chemotherapy regimen as first-line treatment for ES-EPSCC. 10. Adequate organ and marrow function, all screening labs should be performed within 14 days of treatment initiation:\n  1. Haemoglobin ≥9.0 g\u002FdL\n  2. Absolute neutrophil count (ANC) ≥1.0 × 109 \u002FL\n  3. Platelet count ≥75 × 109\u002FL\n  4. Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). \\\u003C\\\u003CThis will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\\>\\>\n  5. AST (SGOT)\u002FALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which\n  6. case it must be ≤5x ULN 11. Measured creatinine clearance (CL) \\>40 mL\u002Fmin or Calculated creatinine CL\\>40 mL\u002Fmin by the Cockcroft- Gault formula. 12. Availability of an archived tumor tissue block at baseline. 13. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female premenopausal patients. 14. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with CT o MRI, suitable for repeated measurements as per RECIST 1.1 criteria. 15. Body weight \\>30 kg\n\n     Exclusion Criteria:\n* Subjects with active, known or suspected autoimmune disease requiring systemic treatment (systemic steroids or immunosuppressive agents) prior 14 days before the first dose of durvalumab.\n\nThe following are exceptions to this criterion:\n\n* Intranasal, inhaled, topical steroids or local steroid injections (eg, intra articular injection).\n* Systemic corticosteroids at physiologic doses not to exceed 10 mg\u002Fday of prednisone or its equivalent.\n* Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).\n* Premedication with steroids for chemotherapy is acceptable\n* Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.\n* Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.\n* Any history of radiotherapy prior to systemic therapy. Radiation therapy for palliative care (ie, bone metastasis) is allowed but must be completed before first dose of the study medication.\n* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \\[eg, colitis or Crohn's disease\\], diverticulitis with the exception of diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, and uveitis, etc\\]).\n\nThe following are exceptions to this criterion:\n\n* Patients with vitiligo or alopecia\n* Patients with hypothyroidism (eg, following Hashimoto syndrome) and stable on hormone replacement\n* Any chronic skin condition that does not require systemic therapy\n* Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician\n* Patients with celiac disease controlled by diet alone\n\n  * Major surgical procedure within 28 days prior to the first dose of investigational product. Local surgery of isolated lesions for palliative intent is acceptable.\n  * History of leptomeningeal carcinomatosis.\n  * History of Human Immunodeficiency Virus (HIV) (HIV 1\u002F2 antibodies).\n  * Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \\[qualitative\\] is detected).\n  * Receipt of live, attenuated vaccine within 30 days prior to the first dose of investigational product.\n\nPatients, if enrolled, should not receive live vaccine whilst receiving the investigational product and up to 30 days after the last dose of investigational product.\n\n* Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent\n* History of allogenic organ transplantation.\n* Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)\n* Female patients with a positive pregnancy test at enrollment or prior to administration of study medication\n* Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy (for more information, refer to paragraph 10.8) .",{"count":281,"type":21},66,[103],"This is a phase II, single-arm, multicenter study to evaluate the activity and safety of durvalumab in combination with carboplatin or cisplatin plus etoposide in patients with treated ES-EPSCC.",[285],"Extrapulmonary Small Cell Carcinoma",[287,288],"EXTRAPULMONARY SMALL CELL CARCINOMA (EPSCC)","DURVALUMAB","2024-06-12",{"date":291,"type":33},"2024-06-18",{"date":293,"type":33},"2024-01-16",{"date":295,"type":21},"2028-01-01",{"name":39,"class":40},{"id":298,"slug":299,"hasResults":11,"nctId":300,"briefTitle":301,"officialTitle":302,"acronym":303,"eligibilityCriteria":304,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":305,"targetDuration":4,"studyType":101,"phases":307,"briefSummary":308,"conditions":309,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":311,"lastUpdatePostDateStruct":312,"startDateStruct":314,"completionDateStruct":316,"leadSponsor":318,"locationsCount":163},"100548214","phase-2-durvalumab-with-carboplatin-and-etoposide-chemotherapy-in-pulmonary-large-cell-neuroendocrine-carcinoma-lcnec-100548214","NCT06418087","Durvalumab With Carboplatin and Etoposide Chemotherapy in Pulmonary Large-cell Neuroendocrine Carcinoma (LCNEC)","A Multicenter Phase II, Single Arm Study of Durvalumab (MEDI 4736) With Carboplatin Plus Etoposide for 4 Cycles Followed by Durvalumab Maintenance in Patients With Metastatic Pulmonary Large-cell Neuroendocrine Carcinoma (LCNEC)","DUPLE","Inclusion Criteria:\n\n* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n* Written informed consent and any locally required authorization obtained from the patient\u002Flegal representative prior to performing any protocol-related procedures, including screening evaluations.\n* Age ≥18 years at the time of study entry\n* Histologically or cytologically (cell blocks only; smears are not acceptable) documented pulmonary large-cell neuroendocrine carcinoma (LCNEC)\n* Stage IV disease or unresectable stage IIIB, which cannot be safely encompassed in a single RT field (e.g. supraclavicular N3, T4 by infiltration of vertebral body), according to the AJCC 8th edition Cancer Staging Manual\n* Body weight \\>30 kg\n* No prior chemotherapy or treatment with another systemic anti-cancer agent. Patients who have received prior chemoradiotherapy for locally advanced pulmonary LCNEC must have been treated with curative intent and experienced a treatment-free interval of at least 6 months from last chemotherapy, radiotherapy or chemoradiotherapy cycle to disease relapse, progression, or diagnosis of metastatic LCNEC. In this case, all toxicity from previous treatments should be resolved and no cumulative toxicity of grade \\>1 should be present (see also Section 4.2 \"Exclusion criteria\").\n* No need for concomitant chest irradiation\n* ECOG performance status 0-1\n* Life expectancy ≥ 12 weeks\n* At least one lesion measurable according to RECIST v 1.1 outside of the CNS, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements\n* Adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1500\u002FµL, hemoglobin ≥9 g\u002FdL (5.58 mmol\u002FL), and platelets ≥100,000\u002FµL.\n* Adequate hepatic and renal functions:\n* Total bilirubin \\\u003C 1.5 times the upper limits of normal \\[ULN\\]\n* AST (SGOT)\u002FALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN\n* Serum creatinine ≤1.5 times the ULN or creatinine clearance, calculated according to the formula of Cockcroft and Gault \\> 60 ml\u002Fmin\n* The patient has adequate coagulation function as defined by International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) (PTT\u002FaPTT) \\\u003C 1.5 x ULN.). Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤3.0.\n* Female patients must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:\n* Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments\n* Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution\n* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation\n* For female patients of childbearing potential, agreement (by patient and\u002For partner) to use a highly effective form of contraception that results in a low failure rate (\\\u003C 1% per year) when used consistently and correctly, and to continue its use for 6 months after the last dose of chemotherapy or 90 days after the last dose of durvalumab, whichever occurs last. Such methods include: combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, and vasectomized partner (on the understanding that this is the only one partner during the whole study duration).\n* Male patients who are sexually active must be willing to use barrier contraceptives (i.e., by use of condoms) during sex with all partners during treatment with chemotherapy and for at least 6 months after the final dose of chemotherapy or 90 days after the last dose of durvalumab, whichever occurs last, to avoid exposing the embryo. Men must refrain from donating sperm during this same period\n* Ability to comply with the study protocol, in the investigator's judgment\n\nExclusion Criteria:\n\n* Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is required within 4 weeks prior to randomization) requiring immediate radiotherapy for palliation. Patients with asymptomatic CNS lesions are eligible, provided that all of the following criteria are met:\n* The patient has no history of intracranial hemorrhage, spinal cord hemorrhage or hemorrhagic intracranial lesions\n* At least 14 days between the end of stereotactic radiotherapy or whole brain radiotherapy and initiation of study treatment, or at least 28 days between neurosurgical resection and initiation of study treatment\n* The patient is on a dose of corticosteroids ≤ 10 mg of oral prednisone or equivalent; anticonvulsant therapy at a stable dose is permitted\n* Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla or spinal cord)\n* There is no evidence of interim progression between completion of CNS directed therapy (if administered) and initiation of study treatment\n* History of leptomeningeal disease\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures\n* Patients with indwelling catheters (e.g., Pleura-Cath) are allowed.\n* Uncontrolled or symptomatic hypercalcemia (ionized calcium \\> 1.5 mmol\u002FL, calcium \\> 12 mg\u002FdL or corrected calcium \\> ULN)\n* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C\n* Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \\[anti-HBc\\] and absence of HBsAg) are eligible.\n* Patients positive for hepatitis C (HCV) antibody are eligible if polymerase chain reaction is negative for HCV RNA.\n* Significant traumatic injury or radiotherapy involving an extensive field within the last 4 weeks prior to first dose of study treatment or anticipation of the need for major surgery during study treatment. Palliative radiotherapy to a limited field is allowed if concluded at least 2 weeks prior enrolment.\n* Other malignancies (previous or current), except for adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, localized prostate cancer surgically treated with curative intent or ductal carcinoma in situ treated surgically treated with curative intent or if previous malignancy was more than 5 years prior and there are no signs or symptoms of recurrence\n* Major surgery (including open biopsy) within 28 days prior to first dose of protocol therapy, or minor surgery\u002Fsubcutaneous venous access device placement within 7 days prior to the first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial.\n* Prior allogeneic stem cell or solid organ transplantation.\n* Patients with any underlying medical condition that might be aggravated by treatment or which cannot be controlled i.e. patients with active serious infection, uncontrolled diabetes mellitus, pericardial effusion.\n* Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment other than those in the present study. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.\n* Treatment with any other investigational agent within 30 days prior to starting study treatment, or concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study\n* Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications\n* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \\[e.g., colitis or Crohn's disease\\], diverticulitis \\[with the exception of diverticulosis\\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\\]). The following are exceptions to this criterion:\n* Patients with vitiligo or alopecia\n* Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement\n* Any chronic skin condition that does not require systemic therapy\n* Patients without active disease in the last 5 years may be included but only after consultation with the study physician\n* Patients with celiac disease controlled by diet alone\n* History or active autoimmune neurologic paraneoplastic syndrome (e.g. non-infectious encephalitis, Lambert-Eaton syndrome etc.) or any other immune-mediated paraneoplastic syndrome.\n* Patients with SIADH or ectopic ATCH production are allowed on trial\n* Patient has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.\n* History of idiopathic pulmonary fibrosis, including pneumonitis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Prior therapy with any anti-PD-1, anti-PD-L1including durvalumab, or anti-PD-L2 agent and anti-CTL-A4 agent.\n* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \\[IL-2\\]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment.\n* Any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization. The following are exceptions to this criterion:\n* Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)\n* Systemic corticosteroids at physiologic doses not to exceed 10 mg\u002Fday of prednisone or its equivalent\n* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)\n* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.\n* History of allergies or hypersensitivity to any study drugs or study drug components or CHO derived products.\n* The patient is pregnant or breast-feeding\n* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria\n* Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.\n* Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with carboplatin, etoposide or durvalumab may be included only after consultation with the Study Physician.\n* Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 6 months after last chemotherapy dose or 90 days after the last dose of durvalumab, whichever occurs last. Patients should refrain from donating sperm from the start of dosing until 4 months after discontinuing study treatment.\n* Patients should not donate blood whilst on this study",{"count":306,"type":21},49,[103],"A prospective multicenter, single-arm phase II study enrolling treatment-naïve patients with metastatic pulmonary large-cell neuroendocrine carcinoma (LCNEC)",[310],"Pulmonary Large-cell Neuroendocrine Carcinoma","2024-05-13",{"date":313,"type":33},"2024-05-16",{"date":315,"type":33},"2022-05-27",{"date":317,"type":21},"2026-12-31",{"name":39,"class":40},""]