[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"large-cell-neuroendocrine-carcinoma-of-the-lung\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:large-cell-neuroendocrine-carcinoma-of-the-lung":37},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,55,92,120,144],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":27,"conditions":28,"keywords":40,"overallStatus":42,"whyStopped":4,"lastUpdateSubmitDate":43,"lastUpdatePostDateStruct":44,"startDateStruct":47,"completionDateStruct":49,"leadSponsor":51,"locationsCount":54},"100578684","phase-1-radiation-combined-with-bispecific-t-cell-engager-in-dll3-expressing-tumors-100578684",false,"NCT06814496","Radiation Combined With BIspecific T-Cell Engager in DLL3 Expressing Tumors","RAdiation comBined With BIspecific T-Cell Engager in DLL3 Expressing Tumors (RABBIT) Study: A Phase I\u002FII Study of AMG757 \u002F Tarlatamab and Concurrent Radiation Therapy in Tumors With High Prevalence of DLL3","RABBIT","Inclusion Criteria:\n\n1. Subject has provided informed consent\u002Fassent prior to initiation of any study specific activities\u002Fprocedures.\n2. Subjects ≥ 18 years of age at the time of signing the informed consent.\n3. Histologically or cytologically confirmed relapsed\u002Frefractory:\n\n   1. SCLC\n   2. Other tumors of small cell histology\n   3. High grade \u002F poorly differentiated neuroendocrine histology tumor histologies with high prevalence of DLL3 (≥50% prevalence of ≥1% positivity), including but not limited to: melanoma, medullary thyroid cancer, esthesioneuroblastoma, bladder cancer, testicular cancer, glioblastoma multiforme, cervical cancer; large cell neuroendocrine tumor of lung, non-small cell lung cancers with mixed neuroendocrine features, and Merkel cell carcinoma OR\n   4. DLL3+ (≥1% by IHC) Note: If patients are DLL3 negative per IHC but have a DLL3 prevelant tumor type, they will be allowed to enroll on the study.\n4. Subjects who progressed or recurred after at least one line of therapy and are considered treatment refractory per standard of care.\n5. Subjects willing to provide archived tumor tissue samples (formalin fixed, paraffin embedded \\[FFPE\\] sample). If no archived tumor tissue is available, we request to undergo pretreatment tumor biopsy. Subjects who do not have archived tumor tissue available and are unable or unwilling to undergo a pretreatment tumor biopsy due to extenuating circumstances (i.e., cannot be performed safely or inaccessible, as determined by the investigator) may be allowed to enroll without a tumor biopsy upon agreement with sponsor.\n6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n7. Minimum life expectancy of 12 weeks.\n8. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.\n9. Measurable lesions as defined per RECIST 1.1 within 28 days prior to the first dose of tarlatamab.\n10. Eligible for external beam radiation therapy to a previously unirradiated, measurable lesion as per standard of care.\n\n    1. For the concurrent \u002F sequential cohort of extracranial RT sites:\n\n    i. A minimum of 10 subjects with thoracic lesions (lung, mediastinum, thoracic spine, rib, or other thoracic sites) will be treated ii. Subjects with treated brain metastases are eligible (untreated brain metastases are ineligible) provided they meet the following criteria:\n\n\u003C!-- -->\n\n1. Definitive therapy was completed at least 2 weeks prior to the first dose of tarlatamab.\n2. There is no evidence of radiographic central nervous system (CNS) progression following therapy and by the time of study screening.\n3. Patients manifesting progression in lesions previously treated with stereotactic radiosurgery may still be eligible if pseudoprogression can be demonstrated by appropriate means.\n4. Any CNS disease is asymptomatic for at least 7 days (unless symptoms are deemed irreversible by the investigator), the patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the subject is off or on stable doses of anti-epileptic drugs for malignant CNS disease for at least 7 days.\n\n   b. For the concurrent\u002Fsequential cohort of cranial RT sites: i. Previously untreated brain lesions \u002F metastases are eligible ii. Subjects with previously irradiated brain lesions are eligible provided they meet one of the following criteria:\n\n\u003C!-- -->\n\n1. Prior PCI or whole brain radiation therapy per standard of care with new and\u002For recurrent brain metastases to be treated with SRS or hfSRT\n2. Prior course(s) of SRS or hfSRT or other localized therapy with new lesion(s) to be treated with whole brain radiation therapy iii. Whole brain re-irradiation will be ineligible iv. Re-irradiation with SRS or hfSRT of previously irradiated lesion with SRS or hfSRT will be ineligible v. Craniospinal irradiation will not be allowed c. For the tarlatamab monotherapy cohort: i. Patient must have at least one measurable lesion, however that lesion does not need to be amenable to RT\n\n1\\. Patients with previously irradiated lesions that have recurred or progressed are eligible 11. Adequate organ function, defined as follows:\n\na. Hematological function: i. Absolute neutrophil count ≥ 1.5 x 109\u002FL ii. Platelet count ≥ 100 x 109\u002FL iii. Hemoglobin \\> 9 g\u002FdL (90 g\u002FL) b. Coagulation function: i. Prothrombin time (PT)\u002Finternational normalized ratio (INR) and partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) ≤ 1.5 x institutional upper limit of normal (ULN). Subjects on chronic anticoagulation therapy who do not meet the criteria above may be eligible to enroll after discussion with the medical monitor.\n\nc. Renal function: i. Estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculation \\> 30 mL\u002Fmin\u002F1.73 m2 d. hepatic function: i. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) \\\u003C 3 x ULN (or \\\u003C 5 x ULN for subjects with liver involvement) ii. Total bilirubin \\\u003C 1.5 x ULN (or \\\u003C 2 x ULN for subjects with liver metastases) e. Pulmonary function: i. No clinically significant pleural effusion ii. Baseline oxygen saturation \\> 90% on room air f. cardiac function (if obtained as part of standard of care): i. Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no clinically significant electrocardiogram (ECG) findings\n\nExclusion Criteria:\n\nRe-irradiation, unless it is SRS\u002FhfSRT after whole-brain radiation therapy (WBRT) or PCI or WBRT after SRS\u002FhfSRT; re-irradiation of same lesion, unless verified with the Principal Investigator; patients with lesions not amenable to RT (including previously irradiated) will be only allowable on the tarlatamab monotherapy cohort.\n\nDisease Related\n\n1. Subjects are excluded from the study if any of the following criteria apply:\n\n   1. No lesion(s)\u002Fsite(s) amenable to radiation therapy (only eligible for tarlatamab monotherapy if open)\n   2. Planned re-irradiation of a previously irradiated site\n   3. Leptomeningeal disease requiring craniospinal irradiation\n2. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.\n3. Subjects who experienced recurrent pneumonitis (grade 2 or higher) or severe, life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.\n4. Unresolved toxicity from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1, or to levels dictated in the eligibility criteria with the exception of alopecia or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for \\> 21 days) which may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and Amgen.\n\nOther Medical Conditions\n\n1. Myocardial infarction and\u002For symptomatic congestive heart failure (New York Heart Association \\> class II) within 12 months of first dose of tarlatamab.\n2. History of arterial thrombosis (i.e., stroke or transient ischemic attack) within 12 months of first dose of tarlatamab.\n3. Subject with symptoms and\u002For clinical signs and\u002For radiographic signs that indicate an acute and\u002For uncontrolled active systemic infection within 7 days prior to the first dose of tarlatamab.\n\n   NOTE: Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. Subjects requiring oral antibiotics who have been afebrile \\> 24 hours, have no leukocytosis and have no clinical signs of infection are eligible. Subjects who meet these criteria and who were previously on IV antimicrobials should have been off IV antimicrobials for \\> 48 hours.\n4. History of hypophysitis or pituitary dysfunction.\n5. Exclusion of hepatitis infection based on the following results and\u002For criteria:\n\n   a. Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B).\n\n   b. Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.\n\n   c. Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.\n6. Major surgery requiring hospitalization for more than 3 days within 28 days of first dose of tarlatamab.\n7. Evidence of interstitial lung disease or active, non-infectious pneumonitis.\n8. Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study.\n9. Human immunodeficiency virus (HIV) infection.\n\n   1. Subjects with HIV infection on antiviral therapy and undetectable viral load are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on study per local or institutional guidelines.\n\nPrior\u002FConcomitant Therapy\n\n1. Subject received prior therapy with tarlatamab.\n2. Prior anti-cancer therapy within 30 days prior to first dose of tarlatamab.\n\n   Exceptions:\n\n   a. Subjects who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to grade ≤ 1.\n3. Has a diagnosis of immunodeficiency (i.e., positive\u002Fnon-negative test for human immunodeficiency virus) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of tarlatamab.\n4. The following vaccines (live and live-attenuated vaccines) are excluded during the following study periods:\n\n   1. Screening and during study treatment: Live and live-attenuated vaccines are prohibited within 28 days prior to the first dose of tarlatamab and for the duration of the study.\n   2. Live viral non-replicating vaccine (i.e., Jynneos) for Monkeypox infection is allowed during the study (except during cycle 1) in accordance with local standard of care (SOC) and institutional guidelines.\n   3. End of study treatment: Live and live-attenuated vaccines can be used when at least 60 days (5 x half-life of tarlatamab) have passed after the last dose of tarlatamab.\n\nOther Exclusions\n\n1\\. Female subjects of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 60 days after the last dose of tarlatamab. Contraception methods for female subjects include:\n\n1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)\n2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, and implantable)\n3. Intrauterine device\n4. Intrauterine hormonal-releasing system\n5. Bilateral tubal ligation\u002Focclusion\n6. Vasectomized partner (provided that partner is the sole sexual partner of the female subject of childbearing potential and that the vasectomized partner has received medical assessment of the surgical success)\n7. Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments; the reliability of sexual abstinence must be evaluated in relation to the duration of the trial and the preferred and usual lifestyle of the subject) 2. Female subjects who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of tarlatamab.\n\n   3\\. Female subjects planning to become pregnant while on study through 60 days after the last dose of tarlatamab.\n\n   4\\. Female subjects of childbearing potential with a positive pregnancy test assessed at screening and\u002For day 1 by a highly sensitive urine or serum pregnancy test.\n\n   5\\. Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception (use a condom) during treatment and for an additional 60 days after the last dose of tarlatamab.\n\n   6\\. Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 60 days after the last dose of tarlatamab.\n\n   7\\. Male subjects unwilling to abstain from donating sperm during treatment and for an 60 days after the last dose of tarlatamab.\n\n   8\\. Subject has known sensitivity to any of the products or components to be administered during dosing.\n\n   9\\. Subject likely to not be available to complete all protocol-required study visits or procedures, and\u002For to comply with all required study procedures (i.e., Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.\n\n   10\\. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.","ALL","18 Years","99 Years",{"count":21,"type":22},30,"ESTIMATED","INTERVENTIONAL",[25,26],"PHASE1","PHASE2","Phase I study to examine safety of the addition of concurrent tarlatamab with standard palliative and consolidative RT regimens , with a main cohort of N=20-24 patients with extracranial anatomic radiation sites.\n\nI) After lead in of 10 patients demonstrating safety of treatment, allow for expansion to cranial sites of disease (N=6-10) with continued enrollment in main cohort II) If toxicity criteria is not met in concurrent RT tarlatamab cohort, we will continue with sequential RT, either A) delivered within 7 days prior to cycle 1 day 1, or B) delivered during cycle 1 -2 but with pre- and post-RT washout of 7 days with no drug during RT, to examine safety in a temporally spaced setting.\n\nIII) If sequential tarlatamab and radiation is not deemed safe, we would allow for continued enrollment to assess efficacy of drug sans radiation treatment, enriching for tumors not of small cell lung cancer histology and allowing for patients without sites amenable to RT.\n\nA nested phase II study will attempt to assess for ORR and safety of study intervention amongst tumors not of small cell lung cancer histology.",[29,30,31,32,33,34,35,36,37,38,39],"Melanoma","Medullary Thyroid Cancer","Sinonasal Undifferentiated Carcinoma","Esthesioneuroblastoma","Bladder Cancer","Testicular Cancer","Glioblastoma Multiforme","Cervical Cancer","Large Cell Neuroendocrine Carcinoma of the Lung","Non Small Cell Lung Cancer","Merkel Cell Carcinoma",[41],"DLL3 Expressing tumors","RECRUITING","2026-05-19",{"date":45,"type":46},"2026-05-20","ACTUAL",{"date":48,"type":46},"2025-09-08",{"date":50,"type":22},"2030-05",{"name":52,"class":53},"University of Arizona","OTHER",2,{"id":56,"slug":57,"hasResults":11,"nctId":58,"briefTitle":59,"officialTitle":60,"acronym":4,"eligibilityCriteria":61,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":62,"enrollmentInfo":63,"targetDuration":4,"studyType":23,"phases":65,"briefSummary":66,"conditions":67,"keywords":71,"overallStatus":42,"whyStopped":4,"lastUpdateSubmitDate":81,"lastUpdatePostDateStruct":82,"startDateStruct":84,"completionDateStruct":86,"leadSponsor":88,"locationsCount":91},"100593460","phase-1-phase-i-study-of-225acac-etn029-in-patients-with-advanced-dll3-expressing-solid-tumors-100593460","NCT07006727","Phase I Study of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors","A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors","Inclusion Criteria:\n\n* Age ≥ 18 years old\n* Patients with one of the following indications:\n* Locally advanced, unresectable, or metastatic SCLC with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy, unless patient was ineligible to receive such therapy. Prior DLL3-targeted therapy is allowed. For dose expansion, patients should have received no more than 2 prior lines of systemic therapy.\n* Dose escalation only: LCNEC of the lung with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy, unless patient was ineligible to receive such therapy.\n* Dose expansion only: Locally advanced, unresectable, or metastatic de novo or castration-resistant, treatment-emergent NEPC with neuroendocrine differentiation confirmed by local histology and NEPC marker expression (e.g., chromogranin, synaptophysin) confirmed by local IHC. Prior PSMA-targeted, Lu-177-based RLT is allowed. Patients must have at least one measurable lesion (per RECIST 1.1) that shows 111In-ETN029 uptake higher than surrounding tissues on SPECT\u002FCT as assessed by the Investigator.\n* Dose expansion only: Locally advanced, unresectable, or metastatic GEP-NEC with disease progression following, or intolerance to, at least 1 line of systemic therapy, including platinum-containing chemotherapy, unless patient was ineligible to receive such therapy. Patients must have at least one measurable lesion (per RECIST 1.1) that shows 111In-ETN029 uptake higher than surrounding tissues on SPECT\u002FCT as assessed by the Investigator.\n\nExclusion Criteria:\n\n* Absolute neutrophil count (ANC) \\\u003C 1.0 x 109\u002FL, hemoglobin \\\u003C 9 g\u002FdL, or platelet count \\\u003C 75 x 109\u002FL\n* QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec\n* eGFR \\\u003C 60 mL\u002Fmin (\\\u003C0.835 mL\u002Fs), calculated using the CKD-EPI 2021 formula or measured\n* Unmanageable urinary tract obstruction or urinary incontinence\n* Presence of leptomeningeal disease, of symptomatic CNS metastases or of CNS metastases that require local CNS-directed therapy\n* History of or current interstitial lung disease or pneumonitis ≥ Grade 2\n* Any prior DLL3-targeted therapy (except for SCLC) and any prior RLT (except for NEPC)\n\nOther protocol-defined inclusion\u002Fexclusion criteria may apply.","100 Years",{"count":64,"type":22},116,[25],"The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \\[225Ac\\]Ac-ETN029 and the safety and imaging properties of \\[111In\\]In-ETN029 in patients aged ≥ 18 years with locally advanced or metastatic DLL3 positive cancers.",[68,37,69,70],"Small Cell Lung Carcinoma","Neuroendocrine Prostate Cancer","Gastroenteropancreatic Neuroendocrine Carcinoma",[72,73,74,75,76,77,78,79,80],"Small Cell Lung Carcinoma (SCLC)","Large Cell Neuroendocrine Carcinoma of the Lung (LCNEC)","Neuroendocrine Prostate Cancer (NEPC)","Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC)","DLL3","Neuroendocrine neoplasms","Radioligand therapy (RLT)","[225Ac]Ac-ETN029","[111In]In-ETN029","2026-05-04",{"date":83,"type":46},"2026-05-05",{"date":85,"type":46},"2025-10-16",{"date":87,"type":22},"2031-08-29",{"name":89,"class":90},"Novartis Pharmaceuticals","INDUSTRY",6,{"id":93,"slug":94,"hasResults":11,"nctId":95,"briefTitle":96,"officialTitle":97,"acronym":98,"eligibilityCriteria":99,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":100,"targetDuration":4,"studyType":23,"phases":102,"briefSummary":103,"conditions":104,"keywords":105,"overallStatus":110,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"locationsCount":4},"100636127","phase-2-a-trial-for-the-treatment-of-advanced-large-cell-neuroendocrine-cancer-of-the-lung-100636127","NCT07561645","A Trial for the Treatment of Advanced Large-Cell Neuroendocrine Cancer of the Lung","A Phase II, Single-arm Trial on the Addition of the DLL3xCD3 Bispecific T-cell Engager Obrixtamig (BI 764532) to Standard-of-care Platinum-based First-line Treatment of Advanced Large-cell Neuroendocrine Carcinoma of the Lung","ALPINE 2","Inclusion Criteria: (main criteria)\n\n1. Patient has provided written informed consent and is able to consent\n2. Patients with pulmonary large-cell neuroendocrine carcinoma (LCNEC) defined by local histology and immunohistochemistry; patients with mixed histology are eligible if LCNEC is the predominant histology, i.e. ≥50%\n3. Patients with locally advanced or metastatic disease without curative treatment options\n4. All patients must have received one, but not more than one, cycle of platinum\u002Fetoposide chemotherapy with or without immune checkpoint inhibitor (standard-of-care; SoC). Other than that, patients must be previously untreated with systemic therapy.\n5. Measurable disease according to RECIST v1.11\n\nExclusion Criteria: (main criteria)\n\n1. Symptomatic brain metastases (Patients with asymptomatic brain metastases are allowed provided they are clinically stable, receiving no or a stable dose of anticonvulsants without steroid treatment for at least 3 weeks.)\n2. Known leptomeningeal disease\n3. Any prior systemic treatment for metastatic disease, except for one cycle of SoC as described under inclusion criteria\n4. Previous treatment with obrixtamig or any anti-DLL3 compound including T-cell engagers and antibody-drug conjugates",{"count":101,"type":22},75,[26],"This phase II clinical trial evaluates the efficacy, safety and tolerability of Obrixtamig in addition to standard of care chemotherapy (Platinum\u002FEtoposide) in LCNEC.",[37],[106,107,108,109],"lung cancer","LCNEC","lung carcinoma","neuroendocrine carcinoma","NOT_YET_RECRUITING","2026-04-27",{"date":113,"type":46},"2026-05-01",{"date":115,"type":22},"2026-07",{"date":117,"type":22},"2032-04",{"name":119,"class":53},"Technische Universität Dresden",{"id":121,"slug":122,"hasResults":11,"nctId":123,"briefTitle":124,"officialTitle":125,"acronym":4,"eligibilityCriteria":126,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":127,"enrollmentInfo":128,"targetDuration":4,"studyType":23,"phases":130,"briefSummary":131,"conditions":132,"keywords":4,"overallStatus":110,"whyStopped":4,"lastUpdateSubmitDate":135,"lastUpdatePostDateStruct":136,"startDateStruct":138,"completionDateStruct":139,"leadSponsor":141,"locationsCount":143},"100632200","phase-2-a-phase-ii-study-of-benmelstobart--anlotinib--chemotherapy-as-first-line-treatment-for-lcnec-and-ep-nec-100632200","NCT07510594","A Phase II Study of Benmelstobart + Anlotinib + Chemotherapy as First-Line Treatment for LCNEC and EP-NEC","A Single-Center, Single-Arm, Phase II Study of Benmelstobart Combined With Anlotinib and Chemotherapy as First-Line Treatment for Large-Cell Neuroendocrine Carcinoma of the Lung and Extrapulmonary Neuroendocrine Carcinoma","Inclusion Criteria:\n\n1. Histologically or cytologically confirmed metastatic LCNEC or EP-NEC (per AJCC 9th Edition);\n2. No prior systemic treatment for locally advanced or metastatic LCNEC or EP-NEC; For patients who have received adjuvant chemo\u002Fradiotherapy, neoadjuvant chemo\u002Fradiotherapy for non-metastatic disease with curative intent, or definitive chemoradiotherapy for locally advanced disease, the interval from the end of chemotherapy, radiotherapy, or chemoradiotherapy to the diagnosis of metastatic NEC must be at least 6 months (calculated from the end date of the last chemotherapy cycle or the end date of the last radiotherapy);\n3. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; Lesions that have received prior radiotherapy can be considered measurable only if there is clear progression after radiotherapy and they are not the only lesion;\n4. Aged 18-75 years;\n5. ECOG Performance Status 0-1;\n6. Life expectancy ≥3 months;\n7. Sufficient hematological and organ function, meeting the following criteria:\n\n   1. Hematology (no blood transfusion or blood products within 14 days, no correction with G-CSF or other hematopoietic stimulants): Absolute Neutrophil Count (ANC) ≥1.5×10⁹\u002FL; Platelet Count (PLT) ≥100×10⁹\u002FL; White Blood Cell (WBC) Count ≥3×10⁹\u002FL;\n   2. Biochemical tests:\n\n      Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5×Upper Limit of Normal (ULN), or ≤5×ULN in patients with liver metastasis; Total Bilirubin (TBIL) ≤1.5×ULN, or ≤3×ULN in patients with Gilbert's syndrome; Creatinine (Cr) ≤1.5×ULN or Creatinine Clearance (CCr) ≥50mL\u002Fmin;\n   3. Coagulation function:\n\n      Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR), or Prothrombin Time (PT) ≤1.5×ULN;\n   4. Doppler ultrasound assessment:\n\n   Left Ventricular Ejection Fraction (LVEF) ≥50%;\n8. Women and men of childbearing potential must agree to use contraceptive measures (e.g., intrauterine device \\[IUD\\], contraceptive pills, or condoms) during the study treatment period and within 6 months after the last dose of study medication; Women must have a negative serum pregnancy test within 7 days before study randomization and must not be breastfeeding;\n9. Subjects voluntarily participate in this study, sign the informed consent form, have good compliance, and cooperate with follow-up.\n\nExclusion Criteria:\n\n1. Patients with brain metastasis and\u002For carcinomatous meningitis (excluding asymptomatic patients or patients with stable condition who have no imaging evidence of new\u002Fenlarged central nervous system metastasis for at least 2 weeks after brain metastasis treatment and have discontinued steroids or anticonvulsants for at least 14 days before the study; If active or new untreated asymptomatic central nervous system metastasis is detected during the screening phase, subjects must receive radiotherapy, or have no imaging evidence of new\u002Fenlarged brain metastasis for at least 2 weeks without treatment);\n2. Prior use of anti-angiogenic drugs such as Anlotinib, Apatinib, Bevacizumab, or immunotherapeutic drugs targeting PD-1, PD-L1, etc.;\n3. History of other malignant tumors within 5 years (except cured carcinoma in situ of the cervix or basal cell carcinoma of the skin);\n4. Factors affecting oral drug administration (dysphagia, post-gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.);\n5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;\n6. Spinal cord compression not cured or relieved by surgery and\u002For radiotherapy, or no clinical evidence of stable condition for ≥1 week after treatment of previously diagnosed spinal cord compression before randomization;\n7. Imaging (Computed Tomography \\[CT\\]\u002FMagnetic Resonance Imaging \\[MRI\\]) showing tumor invasion of large blood vessels or unclear boundary with large blood vessels;\n8. Patients with imaging evidence of tumor invasion around major blood vessels, or judged by the investigator to have a high risk of tumor invading major blood vessels leading to fatal massive hemorrhage during the subsequent study period;\n9. History of severe bleeding tendency or coagulation dysfunction, including but not limited to: clinically significant hemoptysis (hemoptysis \\>1 tablespoon per day) within 3 months before enrollment; or bleeding symptoms or bleeding tendency of significant clinical significance within 4 weeks before randomization, such as gastrointestinal bleeding, hemorrhagic gastric ulcer (including gastrointestinal perforation and\u002For fistula, except for patients with gastrointestinal perforation or fistula who have undergone surgical resection and are eligible for enrollment), unhealed wounds, ulcers, or fractures;\n10. Unresolved treatment-related toxicity (\\>Grade 1) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (except alopecia);\n11. Major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days before randomization;\n12. Arterial\u002Fvenous thromboembolic events (such as cerebrovascular accident \\[including transient ischemic attack\\], deep vein thrombosis, and pulmonary embolism) within 6 months before randomization;\n13. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years before the first dose;\n14. Vaccination with prophylactic or attenuated vaccines within 28 days before the first dose;\n15. Severe allergic reaction to other monoclonal antibodies;\n16. History of psychotropic drug abuse that cannot be abstained from, or mental disorders;\n17. Any severe and\u002For uncontrolled disease:\n\n    1. Poorly controlled blood pressure (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg);\n    2. Grade II or above myocardial ischemia or myocardial infarction, arrhythmia (including corrected QT interval \\[QTc\\] ≥450ms in men and QTc ≥470ms in women); congestive heart failure with New York Heart Association (NYHA) Functional Class II-IV;\n    3. Active or uncontrolled severe infection (≥Grade 2);\n    4. Liver cirrhosis, active hepatitis (hepatitis B: positive hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid \\>ULN; hepatitis C: positive hepatitis C antibody and hepatitis C virus titer \\>ULN);\n    5. Human Immunodeficiency Virus (HIV) positive;\n    6. Poorly controlled diabetes (fasting blood glucose \\>10mmol\u002FL);\n    7. Urinary protein ≥++, and confirmed 24-hour urinary protein \\>1.0g;\n18. Participation in other clinical trials within 28 days before the study;\n19. Other conditions that increase the risk related to study participation or study drugs and are deemed by the investigator to make the patient unsuitable for enrollment.","75 Years",{"count":129,"type":22},48,[26],"To explore the Objective Response Rate (ORR) of Benmelstobart combined with Anlotinib and chemotherapy as first-line treatment for large-cell neuroendocrine carcinoma of the lung (LCNEC) and extrapulmonary neuroendocrine carcinoma (EP-NEC)",[133,134],"Large-Cell Neuroendocrine Carcinoma of the Lung","Extrapulmonary Neuroendocrine Carcinoma","2026-04-01",{"date":137,"type":46},"2026-04-03",{"date":113,"type":22},{"date":140,"type":22},"2027-12-31",{"name":142,"class":53},"Tianjin Medical University Cancer Institute and Hospital",1,{"id":145,"slug":146,"hasResults":11,"nctId":147,"briefTitle":148,"officialTitle":149,"acronym":150,"eligibilityCriteria":151,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":152,"targetDuration":4,"studyType":23,"phases":154,"briefSummary":155,"conditions":156,"keywords":157,"overallStatus":42,"whyStopped":4,"lastUpdateSubmitDate":161,"lastUpdatePostDateStruct":162,"startDateStruct":164,"completionDateStruct":166,"leadSponsor":168,"locationsCount":170},"100546352","phase-2-first-nec-gfpc-01-2022---combination-of-durvalumab-with-etoposide-and-platinum-100546352","NCT06393816","FIRST-NEC (GFPC 01-2022) - Combination of Durvalumab With Etoposide and Platinum","A Multicenter Phase II Study Evaluating the Efficacy and Safety of the Combination of Durvalumab With Etoposide and Platinum as First Line Treatment in Patients With Large-cell Neuroendocrine Carcinomas (LCNECs) of the Lung","FIRST-NEC","Inclusion Criteria:\n\n1. Age ≥ 18 years at the time of study entry;\n2. Locally documented histological diagnosis of Large-Cell NeuroEndocrine Carcinoma of the lung (2021 WHO classification of Lung Tumors );\n3. Patient must have sufficient material to achieve central histological confirmation and exploratory analyses (1 representative FFPE block or at least 10 unstained slides);\n4. Setting of the disease: locally advanced (Stage III) not eligible for loco-regional therapy or metastatic (Stage IV) in first line treatment (8th TNM classification).\n\n   Nota Bene: patients with recurrence of local or locally advanced LCNEC are eligible to the trial provided that recurrence occurs beyond 3 months after the last chemotherapy administration.\n\n   For relapsing patients, tumor material collected at diagnosis can be used for the FIRST-NEC trial if relapse occurs within two years of initial management and if initial histologic tumor material is available.\n5. Measurable disease as per the RECIST 1.1;\n6. Performance Status (PS) of the Eastern Cooperative Oncology Group (ECOG): 0 or 1 ;\n7. Body weight \\> 30Kg;\n8. Must have a life expectancy of at least 12 weeks;\n9. Adequate normal organ and marrow function as defined below:\n\n   * Haemoglobin ≥8.0 g\u002FdL (with or without transfusion)\n   * Absolute neutrophil count (ANC) ≥1.5 × 109 \u002FL\n   * Platelet count ≥100 × 109\u002FL\n   * Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)), or ≤3.0xULN in case of liver metastases.\n\n   Note: this 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   * 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   * For patients undergoing a treatment by cisplatin: measured creatinine clearance (CrCl) ≥60 mL\u002Fmin or Calculated creatinine CrCl ≥60 mL\u002Fmin by the CKD-EPI equation or by 24-hour urine collection for determination of creatinine clearance (CrCl).\n\n   Nota Bene: if creatinine clearance is \\\u003C60 ml\u002Fmin, patients must be treated with carboplatin rather than cisplatin.\n10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:\n\n    * Women \\\u003C50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).\n    * Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation induced menopause with last menses \\>1 year ago, had chemotherapy-induced menopause with last menses \\>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).\n11. Patient (male or female) using a highly effective contraception as defined in during the treatment period and at least up to 6 months after the last administration of chemotherapy or 90 days after the last administration of durvalumab, whichever is longer. Prior to dispensing study drugs, the investigator must confirm and document the patient's (and his\u002Fher partner) use of highly effective contraceptive methods, dates of negative pregnancy tests, and confirm the patient's understanding of the teratogenic potential of study drugs;\n12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n13. Affiliation to a social security system;\n14. 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. Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.\n\nExclusion Criteria:\n\n1. 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 (wash-out period of 28 days);\n2. Patient previously treated for a LCNEC in a metastatic setting;\n3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab;\n4. Any concurrent chemotherapy, Investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable;\n5. Major surgical procedure (as defined by the Investigator) within 21 days prior to the first dose of study drugs; Note: Local surgery or radiotherapy of isolated lesions for palliative intent is acceptable.\n6. History of allogenic organ transplantation;\n7. 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).\n\n   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\n8. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia, interstitial lung disease, peripheral neuropathy \\> grade II, 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;\n9. History of another primary malignancy except for:\n\n   * Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence\n   * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease\n   * Adequately treated carcinoma in situ without evidence of disease, or Gleason ≤6 prostate cancer.\n10. Central Nervous System metastases, unless asymptomatic (including patients treated with anticonvulsants) or previously treated (surgery or radiation therapy combined with corticosteroids ≤10 mg per day) and stable at the time of randomization for at least 15 days;\n11. Carcinomatous meningitis;\n12. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms;\n13. History of active primary immunodeficiency;\n14. Active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA;\n15. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1\u002F2 antibodies) or active tuberculosis infection;\n16. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 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)\n17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.\n\n    Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab.\n18. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients;\n19. Pregnant or breast-feeding woman",{"count":153,"type":22},80,[26],"The primary objective is to determine the efficacy (Progression-Free Rate at 12 months) of durvalumab combined with etoposide and platinum (either cisplatin or carboplatin) for the first-line treatment of patients with advanced LCNEC confirmed by centralized expert-pathologist review",[37],[158,159,160],"Advanced","Large Cell Neuroendocrine Carcinoma","Lung Cancer","2024-08-01",{"date":163,"type":46},"2024-08-02",{"date":165,"type":46},"2024-06-13",{"date":167,"type":22},"2029-09",{"name":169,"class":53},"Centre Leon Berard",31]