[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"leptomeningeal-metastasis\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:leptomeningeal-metastasis":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,25,0,[8,44,72,98,125,150,174,202,230,253,283,305,332,366,391,414,437,459,483,505,526,549,572,593,616],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100549259","phase-1-safety-and-efficacy-of-whole-brain-ldrticiintrathecal-chemotherapy-in-refractory-meningeal-metastasis-of-lung-cancer-100549259",false,"NCT06431685","Safety and Efficacy of Whole Brain LDRT+ICI+Intrathecal Chemotherapy in Refractory Meningeal Metastasis of Lung Cancer","Phase I Study of Whole Brain Low Dose Radiotherapy Combined With ICI and Intrathecal Chemotherapy for Treatment of Refractory Meningeal Metastasis of Lung Cancer","Inclusion Criteria:\n\n1. ≥ 18 years old and ≤ 75 years old;\n2. Patients with a definite diagnosis of leptomeningeal metastasis by cerebrospinal fluid cytology, or patients with clinical diagnosis combined with tumor history, neuroimaging, clinical manifestations, cerebrospinal fluid examination, etc.;\n3. Patients with a clear history of lung carcinoma, including histopathological diagnosis or a combination of cytopathology and imaging, and failure of standard treatment;\n4. Efficacy of extracranial lesions SD;\n5. Patients with no contraindications to craniocranial radiotherapy were judged by radiotherapy doctors. Subjects who agree to receive immunotherapy, Lumbar puncture, intrathecal chemotherapy, and radiotherapy;\n6. Expected survival ≥3 months, PS score ≤3;\n7. Agree to provide cerebrospinal fluid, blood and tissue samples for biomarker testing;\n8. The main organs function normally, no serious blood, heart, lung, liver, kidney, bone marrow and other functional abnormalities and immune deficiency diseases;\n9. One week before enrollment, bone marrow and liver and kidney function met the following criteria:\n\n   ① Hemoglobin ≥80 g\u002FL, neutrophils ≥1.5×10\\^9\u002FL and platelets ≥70×10\\^9\u002FL;\n\n   ② Renal function: Cr≤ULN (upper limit of normal) × 1.5, endogenous creatinine clearance (Ccr)≥55 ml\u002Fmin; Liver function: total bilirubin ≤ULN × 1.5; ALT, AST≤ULN × 2.5; (In case of liver metastasis, total bilirubin should not be higher than 3 times the upper normal limit, and transaminase should not be higher than 5 times the upper normal limit);\n10. The fertile women agreed to use contraception during the study period and for 6 months after the study ended; Patients who tested negative for a serum or urine pregnancy test within 7 days prior to joining the study and were not breastfed; Men who agreed to use contraception during the study period and for 6 months after the study ended\n\nExclusion Criteria:\n\n1. Active autoimmune disease or history of autoimmune diseases;\n2. Congenital or acquired immunodeficiency;\n3. Uncontrolled cardiac clinical symptoms or diseases;\n4. Severe infection or severe comorbidities, such as bleeding peptic ulcer, ileus, heart failure, renal failure, or poorly controlled diabetes;\n5. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;\n6. Other systemic malignancies within the last 5 years;\n7. Allergy to any test drug;\n8. Uncontrolled epilepsy, neurological failure, or severe treatment-related neurological impairment, uncontrollable psychosis, and other conditions deemed unsuitable for inclusion by the investigator;\n9. Pregnant and lactating women, subjects with reproductive capacity are unwilling to take effective contraceptive measures.","ALL","18 Years","75 Years",{"count":20,"type":21},10,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","This phase I study aims to investigate the safety and efficacy of whole brain low dose radiotherapy (WB-LDRT) combined with ICI and intrathecal chemotherapy for treatment of refractory meningeal metastasis of lung cancer.",[27,28,29,30],"NSCLC","Low Dose Radiotherapy","PD-1 Inhibitor","Leptomeningeal Metastasis","RECRUITING","2026-05-04",{"date":34,"type":35},"2026-05-08","ACTUAL",{"date":37,"type":35},"2024-04-25",{"date":39,"type":21},"2026-12-31",{"name":41,"class":42},"Sichuan University","OTHER",1,{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":4,"eligibilityCriteria":50,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":51,"targetDuration":4,"studyType":22,"phases":53,"briefSummary":55,"conditions":56,"keywords":60,"overallStatus":62,"whyStopped":4,"lastUpdateSubmitDate":63,"lastUpdatePostDateStruct":64,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":43},"100635340","phase-2-zorifertinib-plus-intra-ommaya-csf-chemotherapy-for-leptomeningeal-progression-in-nsclc-after-third-generation-egfr-tki-100635340","NCT07551414","Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI","A Prospective Study of Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI Therapy","Inclusion Criteria:\n\n* 1\\. Have fully understood the study and voluntarily signed the Informed Consent Form (ICF).\n\n  2\\. Subjects must be 18-75 years old before signing the Informed Consent Form (ICF).\n\n  3\\. During the screening phase, subjects must be diagnosed with non-small cell lung cancer (NSCLC) and test positive for EGFR-sensitive mutations (L858R and\u002For Exon 19Del).\n\n  4\\. Subjects who developed leptomeningeal progression after treatment with third-generation EGFR-TKIs and have no extracranial progression. The original third-generation EGFR-TKIs may be continued at the original dose or reduced dose.\n\n  5\\. Subjects diagnosed with leptomeningeal metastasis must have positive cerebrospinal fluid (CSF) cytology results. Subjects with negative CSF cytology but clinically diagnosed leptomeningeal metastasis based on symptoms, brain or spinal MRI imaging are also eligible for enrollment.\n\n  6\\. Subjects with both leptomeningeal progression and brain parenchymal progression are allowed to enroll.\n\n  7\\. Have undergone Ommaya reservoir implantation, with confirmation of no surgery-related complications and normal function of the Ommaya reservoir.\n\n  8\\. If accompanied by neurological symptoms, the following conditions must be met: able to take oral medication and swallow drugs; no need to increase hormone dosage to control central nervous system symptoms for at least 1 week prior to study treatment (i.e., symptom stability).\n\n  9\\. All anti-tumor therapy-related toxicities must have recovered to ≤ Grade 1 per CTCAE 5.0 criteria prior to starting study treatment (neurotoxicity related to platinum-based therapy may recover to ≤ Grade 2 per CTCAE 5.0 criteria); alopecia of any grade is allowed for enrollment.\n\n  10\\. Screening period test results must meet the following criteria:\n* Neutrophil count ≥ 1.5 × 10⁹\u002FL\n* Platelet count ≥ 100 × 10⁹\u002FL\n* Hemoglobin ≥ 90 g\u002FL\n* Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (calculated via Cockcroft-Gault formula) ≥ 50 mL\u002Fmin\n* Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN allowed for patients with Gilbert syndrome or liver metastasis)\n* Aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN allowed for patients with liver metastasis)\n* Alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN allowed for patients with liver metastasis) 11. Estimated survival duration ≥ 3 months. 12. Karnofsky Performance Status (KPS) score ≥ 60.\n\nExclusion Criteria:\n\n* 1\\. Subjects with a history of cranial or spinal radiotherapy within 6 months prior to study drug administration are ineligible for enrollment. Radiotherapy for bone metastases within 3 months prior to study drug administration is also not permitted.\n\n  2\\. Subjects who have undergone major surgical procedures (e.g., intrathoracic, intra-abdominal, or pelvic surgery) within 4 weeks prior to the first dose of study treatment, or who have not yet recovered from side effects related to such surgeries, are ineligible for enrollment.\n\n  3\\. Subjects with any other currently active malignant tumor besides NSCLC are excluded.\n\n  4\\. Subjects with clinically significant, uncontrolled cardiac disease and\u002For cardiac events occurring within the past 6 months, such as:\n  1. Myocardial infarction within 6 months prior to screening;\n  2. Documented history of heart failure (NYHA Class III-IV);\n  3. Uncontrolled hypertension: systolic blood pressure ≥160 mmHg and\u002For diastolic blood pressure ≥100 mmHg, regardless of antihypertensive medication use (adjustment of antihypertensive drugs prior to screening is permitted);\n  4. Drug-refractory arrhythmias;\n  5. Screening QTcF \\>470 ms;\n  6. Left ventricular ejection fraction (LVEF) \\\u003C50%. 5. Subjects with gastrointestinal diseases or severe impairment of gastrointestinal function that may significantly affect drug absorption (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).\n\n  6\\. Subjects unable to discontinue the following medications within 1 week prior to study drug administration and during the study period:\n  1. Strong inducers or strong inhibitors of CYP3A4;\n  2. Drugs that may prolong the QT interval or induce torsades de pointes. 7. Subjects with prior or current HIV infection are excluded. HCV antibody-positive subjects may be enrolled if HCV RNA is undetectable (with the lower limit of detection defined per each center's standards) and there is no concurrent hepatitis B virus (HBV) infection. HBV-infected subjects may be enrolled if they meet the following conditions:\n\n  \u003C!-- -->\n\n  1. For active hepatitis B patients: at least 6 weeks of antiviral therapy prior to starting study treatment, with HBV DNA \\\u003C100 IU\u002FmL and ALT\u002FAST levels \\\u003CULN;\n  2. For resolved or chronic hepatitis B patients: at least 2 weeks of prophylactic antiviral therapy prior to starting study treatment, with HBV DNA below 100 IU\u002FmL (e.g., inactive carriers) and ALT\u002FAST levels \\\u003CULN.\n\n  8\\. Pregnant or breastfeeding women; women of childbearing potential must agree to use highly effective contraception during the treatment period and for 3 months after the last dose; fertile men must also use highly effective contraception during the treatment period and for 6 months after the last dose.\n\n  9\\. Subjects with a prior history of interstitial lung disease, including clinically significant radiation pneumonitis (e.g., affecting daily life or requiring therapeutic intervention).\n\n  10\\. Subjects who have previously received zorifertinib or its active pharmaceutical ingredient.\n\n  11\\. Known hypersensitivity to zorifertinib's active ingredients, excipients, or drugs with similar chemical structures or classes.\n\n  12\\. Subjects with other comorbid diseases or factors that, in the investigator's judgment, would pose excessive risk to the subject upon participation in the clinical trial.",{"count":52,"type":21},38,[54],"PHASE2","A Prospective Study of Zorifertinib Combined with Intra-Ommaya Reservoir Cerebrospinal Fluid Chemotherapy for Leptomeningeal Progression in NSCLC Patients After Third-Generation EGFR-TKI Therapy",[57,30,58,59],"NSCLC (Non-small Cell Lung Carcinoma)","EGFR-TKI Sensitizing Mutation","Zorifertinib",[30,27,61,58],"zorifertinib","NOT_YET_RECRUITING","2026-04-22",{"date":65,"type":35},"2026-04-24",{"date":67,"type":21},"2026-05-30",{"date":69,"type":21},"2028-05-30",{"name":71,"class":42},"Cancer Institute and Hospital, Chinese Academy of Medical Sciences",{"id":73,"slug":74,"hasResults":11,"nctId":75,"briefTitle":76,"officialTitle":77,"acronym":4,"eligibilityCriteria":78,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":79,"enrollmentInfo":80,"targetDuration":4,"studyType":22,"phases":82,"briefSummary":84,"conditions":85,"keywords":87,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":89,"lastUpdatePostDateStruct":90,"startDateStruct":92,"completionDateStruct":94,"leadSponsor":96,"locationsCount":43},"100623589","double-dose-third-generation-egfr-tki-plus-bevacizumab-and-intrathecal-chemotherapy-for-refractory-leptomeningeal-metastatic-nsclc-a-phase-ii-study-100623589","NCT07398599","Double-Dose Third-Generation EGFR-TKI Plus Bevacizumab and Intrathecal Chemotherapy for Refractory Leptomeningeal Metastatic NSCLC: A Phase II Study","To Explore the Efficacy and Safety of Double-dose Third-generation EGFR-TKI Combined With Bevacizumab and Intrathecal Chemotherapy in Advanced NSCLC Patients With Progressive Leptomeningeal Metastasis After Prior Standard-dose Third-generation EGFR-TKI Treatment.","Inclusion Criteria\n\n* Aged ≥ 18 years at the time of signing the informed consent form, regardless of gender.\n* Histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), staged as IV according to the 8th edition of the IASLC TNM classification (2015).\n* Presence of EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation).\n* Leptomeningeal metastasis (LM) progression after standard-dose first-, second-, or third-generation EGFR-TKI treatment.\n* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.\n* Adequate major organ function, defined as: hemoglobin (Hb) ≥ 90 g\u002FL, absolute neutrophil count (ANC) ≥ 1.5 × 10\\^9\u002FL, platelet count (PLT) ≥ 100 × 10\\^9\u002FL, white blood cell count (WBC) ≥ 3.0 × 10\\^9\u002FL and ≤ 10.0 × 10\\^9\u002FL; total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 × ULN; creatinine clearance ≥ 50 ml\u002Fmin (for patients with liver metastases, TBIL ≤ 3.0 × ULN, ALT and AST ≤ 5.0 × ULN); activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT) ≤ 1.5 × ULN.\n* At least 21 days since the last radiotherapy (including whole-brain radiotherapy or local radiotherapy for brain metastases).\n* Expected survival ≥ 3 months.\n* Ability to swallow oral medications (or receive crushed medications via gastrostomy tube if unable to swallow).\n* For women: Agreement to use effective contraception (e.g., surgical sterilization or protocol contraception) within 14 days prior to enrollment, during the study, and for 3 months after the last study drug administration.\n* For men: Agreement to use effective contraception (e.g., surgical sterilization or protocol contraception) during the study and for 3 months after the last study drug administration.\n* Voluntary participation, signed informed consent, and willingness to comply with study procedures and protocols.\n\nExclusion Criteria\n\n* Major surgery within 4 weeks prior to the start of study treatment, or need for major surgery during the study.\n* Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).\n* Active bacterial\u002Ffungal\u002Fviral infections requiring intravenous antibiotic therapy.\n* Drug-induced pneumonitis or interstitial lung disease, or evidence of clinically significant active pulmonary disease.\n* Severe cardiovascular events within 6 months prior to enrollment, including cerebrovascular accident, deep vein thrombosis, or pulmonary embolism.\n* Significant cardiovascular disease, such as New York Heart Association (NYHA) class II or higher congestive heart failure, unstable angina, symptomatic arrhythmias requiring treatment, or corrected QT interval (QTcF) \\> 470 ms on consecutive electrocardiograms.\n* History of other systemic malignant tumors within the past 5 years (except for cured basal cell carcinoma, carcinoma in situ of the cervix, and ovarian cancer).\n* Use of drugs or supplements known to be strong inducers of CYP3A4.\n* Known severe allergy to any study drug or its excipients.\n* Pregnancy, lactation, or refusal of effective contraception by patients of childbearing potential.\n* History of definite neurological or psychiatric disorders (including epilepsy and dementia).\n* Other conditions deemed unsuitable for enrollment by the investigator.","99 Years",{"count":81,"type":21},30,[83],"NA","The goal of this clinical trial is to explore the efficacy and safety of double-dose third-generation EGFR-TKI combined with bevacizumab and intrathecal chemotherapy in treating advanced non-small cell lung cancer (NSCLC) patients with leptomeningeal metastasis that progressed after prior standard-dose third-generation EGFR-TKI treatment. It also aims to investigate the correlation between cerebrospinal fluid genetic characteristics and prognosis as well as subsequent efficacy prediction in patients with leptomeningeal metastasis after resistance to standard-dose third-generation EGFR-TKI. The main questions it intends to answer are:\n\nDoes this combined treatment regimen improve leptomeningeal metastasis response rate (LM-ORR) evaluated by RANO-LM? What adverse events occur in patients during the treatment with this combined regimen? Researchers will conduct a single-arm phase II prospective study to assess the effectiveness and safety of the combined treatment, without a control group comparison.\n\nParticipants will:\n\nReceive double-dose third-generation EGFR-TKI (osimertinib 160mg qd, furmonertinib 160mg qd, or almonertinib 220mg qd) + intrathecal pemetrexed (induction phase: 10mg twice a week for 4 weeks; maintenance phase: 10mg once a week for 4 weeks; consolidation phase: 30mg every 4 weeks until disease progression or intolerable toxicity) + bevacizumab 7.5mg\u002Fkg.\n\nUndergo screening assessments within 28 days before enrollment, including tumor imaging, laboratory tests, and cerebrospinal fluid examination.\n\nDuring the treatment period, conduct regular checkups and tests (such as blood routine, blood biochemistry, electrocardiogram, and imaging examinations) according to the protocol (once every 4 weeks in the first two treatment cycles, then once every 8 weeks).\n\nComplete quality of life assessment using the QLQ-C30 scale every 4 weeks and record changes in neurological symptoms and ECOG scores.",[30,86],"Lung Neoplasms, Non-Small Cell Lung Cancer",[30,88],"non-small cell lung cancer","2026-04-21",{"date":91,"type":35},"2026-04-23",{"date":93,"type":35},"2026-02-15",{"date":95,"type":21},"2027-12-30",{"name":97,"class":42},"Second Affiliated Hospital of Nanchang University",{"id":99,"slug":100,"hasResults":11,"nctId":101,"briefTitle":102,"officialTitle":102,"acronym":4,"eligibilityCriteria":103,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":104,"targetDuration":4,"studyType":22,"phases":106,"briefSummary":107,"conditions":108,"keywords":112,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":116,"lastUpdatePostDateStruct":117,"startDateStruct":119,"completionDateStruct":121,"leadSponsor":123,"locationsCount":43},"100619772","pulsatile-high-dose-furmonertinib-in-egfr-mutant-nsclc-with-leptomeningeal-metastasis-100619772","NCT07348965","Pulsatile High-dose Furmonertinib in EGFR-mutant NSCLC With Leptomeningeal Metastasis","Inclusion Criteria:\n\n1. Patients with non-small cell lung cancer (NSCLC) confirmed by histopathological or cytopathological examination\n2. Patients with EGFR exon 19 deletion or exon 21 L858R mutation\n3. Patients with leptomeningeal metastasis (LMD) confirmed by positive cerebrospinal fluid (CSF) cytology (within 28 days prior to the first dose administration) and with at least 1 LMD lesion that can be repeatedly evaluated by magnetic resonance imaging (MRI)\n4. Patients with disease progression after first-line tyrosine kinase inhibitor (TKI) treatment\n5. Aged ≥18 years and ≤85 years, with no gender restrictions.\n6. Sufficient organ function, defined as: absolute neutrophil count ≥ 1.5×10⁹\u002FL, platelet count ≥ 75×10⁹\u002FL, hemoglobin ≥ 90g\u002FL total bilirubin ≤ 1.5×upper limit of normal (ULN) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (for patients with liver metastasis, total bilirubin can be relaxed to ≤ 3×ULN, and ALT\u002FAST can be relaxed to ≤ 5×ULN) serum creatinine ≤ 1.5×ULN or creatinine clearance ≥ 50 mL\u002Fmin (calculated by the Cockcroft-Gault formula)\n7. For patients enrolled in the pharmacokinetic study: no prior treatment with furmonertinib (either in combination or as monotherapy)\n8. Patients who have signed the informed consent form, are willing to receive treatment under this protocol, can adhere to medication administration, and have good compliance.\n\nExclusion Criteria:\n\n1. Unable to complete the baseline assessment form\n2. Complicated with severe or uncontrolled systemic diseases, including active infection, electrolyte disturbance, bleeding tendency, etc.\n3. Pregnant or lactating women, or those with planned pregnancy during the study or within 6 months after the study ends\n4. Presence of central nervous system complications requiring emergency neurosurgical intervention\n5. Suffering from other malignant tumors or having a history of other malignant tumors\n6. Complicated with severe brain diseases or mental illnesses that affect the patient's ability to report symptoms by themselves\n7. Individuals without legal capacity, or those for whom medical or ethical reasons affect the continuation of the study\n8. Other circumstances deemed unsuitable for participation in this study by the researcher.\n9. Patients with a severe allergic diathesis, especially those who have experienced severe drug allergies or other serious adverse reactions during previous treatment with tyrosine kinase inhibitors (TKIs).",{"count":105,"type":21},42,[83],"The goal of this clinical trial is to clarify the efficacy and safety of the high-dose alternate-day furmonertinib in NSCLC with leptomeningeal metastasis. It will also explore the mechanism by which the high-dose alternate-day administration regimen enhances efficacy from a pharmacokinetic perspective, and investigate the impact of co-occurring mutations on the efficacy and prognosis of furmonertinib in the treatment of EGFR-mutant NSCLC with leptomeningeal metastasis. The main questions it aims to answer are:\n\nDoes the high-dose alternate-day administration regimen have definite efficacy? Does the high-dose alternate-day administration regimen have favorable safety? Does the high-dose alternate-day administration regimen improve efficacy by increasing the cerebrospinal fluid (CSF) concentration and CSF penetration rate of the drug? Which co-occurring mutations may affect the efficacy and prognosis of patients with EGFR-mutant NSCLC and leptomeningeal metastasis? Participants will enter Cohort A (320mg qod po) or Cohort B (160mg qd po) to receive furmonertinib based on their own willingness and the clinician's decision, until disease, progression or uncontrollable adverse reactions occur. All patients in Cohort A will undergo efficacy and safety evaluation, with some also participating in pharmacokinetic study; patients in Cohort B will only undergo pharmacokinetic study.\n\nEfficacy and safety evaluation will be conducted through imaging examinations, neurological function assessment scales, quality of life self-assessment scales, and adverse event records. Pharmacokinetic study will be carried out by detecting the plasma concentrations and CSF concentrations of furmonertinib and its active metabolites, and calculating the CSF penetration rate for evaluation.",[109,30,110,111],"NSCLC (Advanced Non-small Cell Lung Cancer)","Furmonertinib","EGFR Activating Mutation",[27,113,114,115],"furmonertinib","leptomeningeal metastasis","cerebrospinal fluid","2026-03-31",{"date":118,"type":35},"2026-04-02",{"date":120,"type":35},"2026-03-01",{"date":122,"type":21},"2028-12-31",{"name":124,"class":42},"Guangzhou University of Traditional Chinese Medicine",{"id":126,"slug":127,"hasResults":11,"nctId":128,"briefTitle":129,"officialTitle":130,"acronym":4,"eligibilityCriteria":131,"healthyVolunteers":11,"sex":16,"minAge":132,"maxAge":4,"enrollmentInfo":133,"targetDuration":4,"studyType":22,"phases":135,"briefSummary":136,"conditions":137,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":140,"lastUpdatePostDateStruct":141,"startDateStruct":143,"completionDateStruct":145,"leadSponsor":147,"locationsCount":43},"100501159","phase-2-intrathecal-pemetrexed-for-leptomeningeal-metastasis-in-egfr-mutant-nsclc-100501159","NCT05805631","Intrathecal Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC","Efficacy of Intrathecal Pemetrexed Combined With Tyrosine Kinase Inhibitor for Treating Leptomeningeal Metastasis in EGFR-Mutant NSCLC After Failure of Osimertinib","Inclusion criteria\n\n* At least 20 years of age.\n* Patients with metastatic non-squamous NSCLC harboring known EGFR activating mutation and with a diagnosis of probable or confirmed LM by the European Association of Neuro-Oncology-European Society for Medical Oncology (EANO-ESMO) guideline. \\[5\\] EGFR activating mutations include exon19 deletion, T790M, L858R, G719X, L861Q, or S768I.\n* Intracranial disease progression after osimertinib use, proved by contrast-enhanced MRI\n* Stable extra-cranial disease status, judged by investigators.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-3 and a minimum life expectancy of 12 weeks\n* Normal bone marrow and organ function as defined below:\n\n  * Marrow: Hemoglobin ≥9gm\u002FdL, ANC ≥1500\u002Fmm3 platelets ≥100,000\u002Fmm3\n  * Hepatic: Serum total bilirubin ≤1.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) ≤3 x ULN.\n  * Renal: Creatinine clearance (Ccr) ≥45 mL\u002Fmin.\n* For female patients of childbearing potential, agreement (by patient and\u002For partner) to use a highly effective form(s) of contraception that results in a low failure rate (\\\u003C 1% per year) when used consistently and correctly, and to continue its use for 5 months after the last dose of IP. 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, vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.\n* Ability to understand and willingness to sign an IRB approved written informed consent document.\n* Willing to provide CSF and plasma samples for ctDNA analysis.\n\nExclusion criteria\n\n* Uncontrolled extra-CNS disease which needs other systemic treatment than EGFR-TKI.\n* Uncontrolled tumor-related pain\n* Uncontrolled or symptomatic hypercalcemia (\\> 1.5 mmol\u002FL ionized calcium or Ca \\> 12 mg\u002FdL or corrected serum calcium \\> ULN). Patients who are receiving denosumab prior to study enrollment must be willing and eligible to receive a bisphosphonate instead while in the study.\n* Malignancies other than NSCLC within 5 years prior to study enrollment, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS \\> 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)\n* On chronic systemic steroid therapy more than 20 mg prednisolone per day (or equivalent) or on any other form of immunosuppressive medication\n* Has received a live-virus vaccination within 30 days of planned treatment start\n* Systemic cytotoxic chemotherapy or major surgery within 2 weeks of the first dose of study medication\n* Active infection requiring therapy\n* History of Human Immunodeficiency Virus (HIV) infection.\n* Hepatitis B carrier: Patients with HBV infection were required to be receiving effective antiviral therapy and have a viral load less than 100 IU\u002FmL at screening\n* Active Hepatitis C\n* Has received intrathecal chemotherapy within 2 weeks before the start of IP\n* Has received whole-brain radiotherapy (WBRT) within 2 weeks before the start of IP\n* Uncontrolled epilepsy\n* History of allergic reaction to intravenous pemetrexed.\n* Severe coagulation abnormality (INR \\> 2).\n* Severe symptomatic hydrocephalus that requires other treatment modalities other than IP\n* Bulky intra-cranial lesion that requires other treatment modalities other than IP","20 Years",{"count":134,"type":21},23,[54],"Leptomeningeal metastasis (LM) is a complication of advanced non-small cell lung cancer (NSCLC). The incidence of LM in NSCLC patients is around 3-5 %, reaching 9.4 % of those with an epidermal growth factor receptor (EGFR) mutation. Generally, the efficacy of systemic treatment for LM is limited due to the blood-brain barrier. Osimertinib has a high central nervous system penetration rate, making it the preferred first-line treatment for EGFR-mutant NSCLC. Previous studies indicated that osimertinib had shown promising efficacy in pretreated patients harboring EGFR mutations and LM. However, intracranial disease progression eventually develops, and the prognosis of patients with LM progression after osimertinib is poor. Recently, intrathecal chemotherapy with pemetrexed (IP) was reported to be an alternative treatment in patients with NSCLC and LM. The results from a phase I\u002FII trial examining the efficacy and safety of IP in patients with EGFR-mutant NSCLC after the failure of previous TKI, and 83% of study enrollees received osimertinib before IP. The clinical response rate was 84.6%, and the median overall survival was 9.0 months. Despite initial promising efficacy, further trials are needed to verify these results. Therefore, the investigators plan to conduct a prospective study to examine the safety and effectiveness of IP combined with EGFR-TKI for patients with EGFR mutant NSCLC after osimertinib failure.",[138,139,30],"Carcinoma, Non-Small-Cell Lung","Epidermal Growth Factor Receptor","2026-03-23",{"date":142,"type":35},"2026-03-24",{"date":144,"type":35},"2024-08-01",{"date":146,"type":21},"2027-12-31",{"name":148,"class":149},"Taipei Veterans General Hospital, Taiwan","OTHER_GOV",{"id":151,"slug":152,"hasResults":11,"nctId":153,"briefTitle":154,"officialTitle":155,"acronym":4,"eligibilityCriteria":156,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":157,"targetDuration":4,"studyType":22,"phases":159,"briefSummary":160,"conditions":161,"keywords":163,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":166,"lastUpdatePostDateStruct":167,"startDateStruct":169,"completionDateStruct":171,"leadSponsor":172,"locationsCount":43},"100567063","phase-1-intrathecal-injection-pemetrexed-and-bevacizumab-in-patients-with-leptomeningeal-metastases-in-nsclc-100567063","NCT06663306","Intrathecal Injection Pemetrexed And Bevacizumab in Patients With Leptomeningeal Metastases in NSCLC","Efficacy and Safety of Pemetrexed Combined With Bevacizumab Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC","Inclusion Criteria:\n\n* Age ≥ 18 years;\n* ECOG PS score 0-3. ECOG PS score 2 or 3 should be due to leptomeningeal metastases.\n* Patients with pathologically diagnosed non-small cell lung cancer with cerebrospinal fluid and\u002For MRI diagnosis of leptomeningeal metastasis(LM);\n* Unsatisfactory efficacy of LM,which defined as disease progression in LM,or LM-related neurological progression, while patients received standard systemic anti-tumor treatment;\n* Expected survival time ≥ 1 month;\n* The laboratory test results meet the following criteria:Hemoglobin ≥ 90 g\u002FL, neutrophil count ≥ 1.5 × 10\\^9\u002FL, platelet count ≥ 100 × 10\\^9\u002FL; Total bilirubin ≤ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN ; Creatinine≤ 2.0 × ULN,or Creatinine clearance rate (CrCl) ≥ 50 mL\u002Fmin;\n* Females of child-bearing potential agree to use contraception during the study period and for 6 months after the completion of the study; patients who have had a negative serum or urine pregnancy test within seven days prior to enrollment in the study and who are not breastfeeding; and males agreeing to use contraception during the study period and for 6 months after the completion of the study;\n* Understand and sign the informed consent form.\n\nExclusion Criteria:\n\n* Positive for human immunodeficiency virus (HIV) ;\n* History of allergy to pemetrexed or bevacizumab;\n* History of pemetrexed and\u002For bevacizumab intrathecal Injection;\n* Presence of contraindication of bevacizumab:\n\n  1. Uncontrolled hypertension(systolic pressure≥150mmHg，or diastolic pressure≥100mmHg；History of hypertensive crisis or hypertensive encephalopathy;\n  2. Urine protein≥2+,or 24-hour urine protein≥2g；\n  3. Unstable angina pectoris, symptomatic congestive heart failure,myocardial infarction within 6 months before enrollment, severe vascular disease, severe uncontrolled arrhythmia;\n  4. Major hemoptysis within the past 1 month; History of coagulation disorders;\n  5. Presence of serious non-healing wounds, ulcers, or bone fractures\n  6. Presence of abdominal fistula, gastrointestinal perforation, or gastrointestinal tract obstruction;\n  7. Presence of macrovascular invasion；\n  8. Some neurological disorders unrelated to tumors，such as intracranial infection,cerebral hemorrhage,cerebral infarction,encephalitis;\n* Brain\u002Fspinal cord radiation therapy within 1 week before enrollment;\n* Pregnant and lactating female;\n* Refuse to use contraception during the study period;\n* Individuals considered by the investigator to be unsuitable for enrollment.",{"count":158,"type":21},19,[24],"This is a prospective, single-arm, phase Ia clinical study, which was designed to evaluate the efficacy and safety of Pemetrexed Combined With Bevacizumab Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC.",[162,30],"Lung Cancer (NSCLC)",[164,27,165],"Leptomeningeal Metastases","Intrathecal Injection","2026-02-26",{"date":168,"type":35},"2026-03-02",{"date":170,"type":35},"2024-12-09",{"date":95,"type":21},{"name":173,"class":42},"Shanghai Chest Hospital",{"id":175,"slug":176,"hasResults":11,"nctId":177,"briefTitle":178,"officialTitle":179,"acronym":4,"eligibilityCriteria":180,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":181,"targetDuration":4,"studyType":22,"phases":182,"briefSummary":183,"conditions":184,"keywords":189,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":194,"lastUpdatePostDateStruct":195,"startDateStruct":197,"completionDateStruct":199,"leadSponsor":201,"locationsCount":43},"100520624","phase-2-trastuzumab-deruxtecan-t-dxd-for-people-with-brain-cancer-100520624","NCT06058988","Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer","Window of Opportunity Assessment of [Fam-]Trastuzumab DERuxtecan-nxki (T-DXd) Brain Tumor Penetration and Efficacy (WOnDER-BT)","Inclusion Criteria:\n\n* Adult patients ≥ 18 years of age with one or more brain tumors planned for neurosurgical resection\u002Fbiopsy\n* Pathologically-documented glioblastoma; or\n* Metastatic cancer that:\n\n  o Has a history of Her2 expression or activating Her2-mutation\n* Her2+ defined as 3+ on IHC\n* Her2-low defined as IHC1+ or 2+ and ISH- according to ASCO-CAP 2018 Her2 testing guidelines52\n* Her2 mutations must be described to be activating, occur at a known hotspot (e.g. exon 20 insertions, S310, G660, R678, L755, D769, L777), or involve the transmembrane, juxtamembrane or tyrosine kinase domains\n* Other untreated brain tumors (and prior radiation, including whole-brain and\u002For stereotactic radiation) are allowed\n* Patients with concomitant leptomeningeal metastasis are eligible provided they have parenchymal brain neoplastic disease requiring resection\u002Fbiopsy\n* Prior treatments:\n\n  * Cohort A: Brain parenchymal metastases in patients with Her2-expressing\u002FERBB2- activating-mutant cancer with no prior T-DXd exposure (T-DXd naïve)\n  * Cohort B: Brain parenchymal metastases in patients with Her2-expressing\u002FERBB2- activating-mutant cancer with prior T-DXd exposure\n  * Cohort C: Recurrent glioblastoma\n  * For all cohorts: no limit on prior CNS radiation or systemic therapy, including Her2- targeting antibody therapy (including trastuzumab, pertuzumab, trastuzumab emtansine)\n* KPS ≥ 60 Or ECOG \\\u003C 2\n* Life expectancy \\>12 weeks\n* Left ventricular ejection fraction ≥50%\n* Adequate bone marrow, renal, hepatic, and coagulation parameters (obtained ≤7 days prior to the first day of study treatment):\n\n  * Absolute neutrophil count (ANC) ≥1.5 × 103\u002FμL (granulocyte-colony stimulating factor administration is not allowed within 1 week prior to C1D1)\n  * Platelet count ≥10.0x104\u002FμL. Note: Participants requiring ongoing transfusions or growth factor support to maintain platelet count ≥10.0x104\u002FμL are not eligible. (Platelet transfusion is not allowed within 1 week prior to C1D1)\n  * Hemoglobin ≥ 8.0 g\u002FdL. Note: Participants requiring ongoing transfusions or growth factor support to maintain hemoglobin ≥8.0 g\u002FdL are not eligible (\\> 8 g\u002FdL in gastric cancer \u002F gastroesophageal cancer indications). (Red blood cell transfusion is not allowed within 1 week prior to C1D1)\n  * Serum albumin ≥ 2.5 g\u002FdL\n  * Creatinine clearance ≥30 mL\u002Fmin, as calculated using the Cockcroft-Gault equation\n  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN) (\\\u003C5x ULN in participants with liver metastases)\n  * Total bilirubin ≤1.5 × ULN) if no liver metastases or \\\u003C3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline\n  * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.0xULN unless on medication known to reversibly alter INR and\u002For aPTT\n* Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU\u002FmL) must be available within 7 days of the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of T-DXd.\n* Women of childbearing potential are defined as those who are not surgically sterile (i.e.\n\nunderwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy). Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.\n\n* Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, presented in Table 1 from the time of screening and must agree to continue using such precautions for 7 months after the last dose of T-DXd. Note: estrogen\u002Fprogesterone is contraindicated in ER+ breast cancer, and in other cancers could increase the risk of DVT. Female patients must refrain from breastfeeding while on study and for 7 months after the last dose of T-DXd.\n* Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose ofT-DXd. Complete heterosexual abstinence for the drug washout period is an acceptable contraceptive method if it is in line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. It is strongly recommended for the female partners of a male patient to also use ≥1 highly effective method of contraception throughout this period, as described in Table 1. In addition, male patients should refrain from fathering a child, or freezing or donating sperm from the time of enrollment until 4 months after the last dose of T-DXd; sperm preservation should be considered prior to enrollment in this study.\n* Female subjects must not donate, or retrieve for their own use, ova from the time of enrollment through at least 7 months after the final study drug administration. Preservation of ova may be considered prior to enrollment in this study.\n* Adequate treatment washout period from prior therapies to allow recovery from any prior treatment-related toxicities before enrollment in the judgment of the Investigator.\n\nTable 1: Highly effective methods of contraception (\\\u003C1% failure rate) Non-Hormonal Methods\n\n* Total heterosexual abstinence (evaluate in relation to the duration of the clinical study and the preferred and usual lifestyle choice of the participant)\n* Vasectomised sexual partner (if partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success)\n* Bilateral tubal occlusion\n* Intrauterine device (provided coils are copper banded)\n\nHormonal Methods\n\n* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (noting relevant contraindications in ER+ breast cancer, and risk of DVT in other cancers)\n* oral\n* intravaginal\n* transdermal\n* Progestogen-only hormonal contraception associated with inhibition of ovulation\n* oral\n* injectable\n* implantable\n* Intrauterine hormone-releasing system (IUS)\n\nExclusion Criteria:\n\n* Contraindication or history of allergic reaction to T-DXd\n* Significant comorbidities as per investigator evaluation\n* Inability to comply with protocol and\u002For unwilling or not available for follow up assessments or any condition which in the investigator's opinion makes the patient unsuitable for study participation\n* Ferrous or other contraindication to MR imaging\n* History of myocardial infarction within 6 months before enrollment\n* History of symptomatic congestive heart failure (New York Heart Association Class II to IV)\n* Corrected QT interval (QTc) prolongation to \\>470 ms (females) or \\>450 ms (male) based on12-lead electrocardiogram (ECG)\n* Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI\n* History of (noninfectious) interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, has current ILD\u002Fpneumonitis, or where suspected ILD\u002Fpneumonitis can not be ruled out by baseline chest CT at Screening.\n* Lung criteria:\n\n  1. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.)\n  2. Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening.\n  3. Prior pneumonectomy (complete)\n* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals\n* Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.\n* Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of T-DXd.\n* Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \\>Grade 2 for at least 3 months prior to \\[randomization\u002Fenrollment\u002FCycle 1 Day 1\\] and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, such as:\n\n  1. Chemotherapy-induced neuropathy\n  2. Fatigue\n  3. Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathies which may include:\n\n  i. Hypothyroidism\u002Fhyperthyroidism ii. Type 1 diabetes iii. Hyperglycemia iv. Adrenal insufficiency v. Adrenalitis vi. Skin hypopigmentation (vitiligo)\n* Known allergy or hypersensitivity to study treatment or any of the study drug excipients. For patients who are allergic to gadolinium-based agents may receive premedication as per institutional protocol or imaged without contrast at the discretion of the Principal Investigator; reactions will be managed per standard institutional protocol\n* History of severe hypersensitivity reactions to other monoclonal antibodies\n* Pregnant or breastfeeding female patients, or patients who are planning to become pregnant.\n* Patients with substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.\n* Multiple primary malignancies within 3 years, with the exception of:\n\n  1. adequately resected non-melanoma skin cancer\n  2. carcinoma in situ of the cervix\n  3. Smoldering pre-malignant or malignant conditions with minimal concern for CNS or extracranial progression during treatment such as CLL or MGUS based on the assessment of the treating provider\n  4. curatively treated in-situ disease\n  5. other solid tumors curatively treated\n  6. contralateral breast cancer \\[patients with metastatic breast cancer\\].\n* A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART)",{"count":81,"type":21},[54],"The purpose of this study is to find out how much tratuzumab deruxtecan (T-DXd) can penetrate the tumor when injected into the body, and whether T-DXd may be an effective treatment for brain cancers that express the HER2 protein.",[185,186,187,30,188],"Brain Cancer","Glioblastoma","Metastatic Cancer","Recurrent Glioblastoma",[185,186,187,30,188,190,191,192,193],"Trastuzumab Deruxtecan","T-DXd","22-208","Memorial Sloan Kettering Cancer Center","2026-02-19",{"date":196,"type":35},"2026-02-23",{"date":198,"type":35},"2023-09-22",{"date":200,"type":21},"2027-09-22",{"name":193,"class":42},{"id":203,"slug":204,"hasResults":11,"nctId":205,"briefTitle":206,"officialTitle":207,"acronym":4,"eligibilityCriteria":208,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":209,"targetDuration":4,"studyType":22,"phases":211,"briefSummary":212,"conditions":213,"keywords":214,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":221,"lastUpdatePostDateStruct":222,"startDateStruct":224,"completionDateStruct":226,"leadSponsor":228,"locationsCount":43},"100538892","phase-2-intrathecal-pemetrexed-for-leptomeningeal-metastasis-from-lung-adenocarcinoma-that-progressed-after-osimertinib-100538892","NCT06296745","Intrathecal Pemetrexed for Leptomeningeal Metastasis From Lung Adenocarcinoma That Progressed After Osimertinib.","An Open-label, Single-arm, Phase II Trial of Intrathecal Pemetrexed for Leptomeningeal Metastasis From Lung Adenocarcinoma That Progressed After a Double Dose of Third-generation TKIs, Including Osimertinib","Inclusion Criteria:\n\n1. Male or female aged between 18 and 75 years.\n2. Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del).\n3. Confirmed diagnosis of leptomeningeal metastasis according to ESMO\u002F EANO guidelines.\n4. Progression after previous double doses of third-generation TKIs such as Osimertinib.\n5. Normal liver and kidney function; WBC≥4000\u002Fmm3, Plt≥100000\u002Fmm3.\n6. No history of severe nervous system disease.\n7. No severe dyscrasia.\n\nExclusion Criteria:\n\n1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.\n2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.\n3. Patients with poor compliance or other reasons that were unsuitable for this study",{"count":210,"type":21},36,[54],"Pemetrexed is one of the first-line chemotherapeutic agents for non-squamous non-small cell lung cancer (NSCLC). Since 2017, intrathecal pemetrexed has shown good efficacy for patients with leptomeningeal metastases from NSCLC. It has been recommended as the preferred drug for intrathecal chemotherapy by the Chinese Society of Clinical Oncology (CSCO) guidelines. Tyrosine kinase inhibitors (TKIs) play a promising role in treating non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. An international multi-center clinical study published in 2019 confirmed that double dose of osimertinib showed significant improvement in leptomeningeal metastases from NSCLC with EGFR exon 19 deletion or exon 21 L858R\u002FT790M mutation. It makes TKIs the mainstay of treatment for patients with EGFR-mutant NSCLC with leptomeningeal metastases. However, the choice of treatment after resistance to targeted therapy is a hot topic in clinical practice, with 78% of patients in the study above who responded to double-dose osimertinib still showing progression at the time of follow-up. The purpose of this study was to observe the safety and efficacy of intrathecal pemetrexed for leptomeningeal metastasis from lung adenocarcinoma that progressed after a double dose of a third-generation TKI such as osimertinib.",[30],[215,216,217,218,219,220],"Leptomeningeal metastasis","Intrathecal chemotherapy","Pemetrexed","Osimertinib","Epidermal growth factor receptor mutation","Non-small-cell lung cancer","2026-01-28",{"date":223,"type":35},"2026-01-30",{"date":225,"type":35},"2025-09-01",{"date":227,"type":21},"2027-03-20",{"name":229,"class":42},"Guangzhou Medical University",{"id":231,"slug":232,"hasResults":11,"nctId":233,"briefTitle":234,"officialTitle":235,"acronym":4,"eligibilityCriteria":236,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":237,"targetDuration":4,"studyType":22,"phases":239,"briefSummary":241,"conditions":242,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":244,"lastUpdatePostDateStruct":245,"startDateStruct":247,"completionDateStruct":249,"leadSponsor":251,"locationsCount":43},"100533764","phase-4-intrathecal-chemotherapy-through-ommaya-reservoir-upon-her-2-negative-breast-cancer-with-leptomeningeal-metastasis-100533764","NCT06230055","Intrathecal Chemotherapy Through Ommaya Reservoir Upon Her-2 Negative Breast Cancer With Leptomeningeal Metastasis","Clinical Outcome and Quality of Life of Intrathecal Chemotherapy Through Ommaya Reservoir in Combination With Systematic Chemotherapy Versus Systematic Chemotherapy Upon Her-2 Negative Breast Cancer With Leptomeningeal Metastasis (CONQUER)","Inclusion Criteria:\n\n1. Male or female aged 18 years or above;\n2. Can understand the purpose of clinical trials and the benefits and risks, voluntarily participate in and sign the informed consent\n3. The physical status score of the Eastern Oncology Consortium (ECOG) was ≤3;\n4. HER2-metastatic breast cancer confirmed histologically or cytologically (HER2- is defined as either a standard immunohistochemical (IHC) test result of 0 or 1+, or an IHC test result of 2+ and a negative ISH test result);\n5. Failure of standard treatment, or intolerance to standard treatment;\n6. pial metastasis is present, which is defined as meningeal metastasis confirmed by malignant tumor cells found in cerebrospinal fluid cytology; Or clinical symptoms\u002Fsigns suggest meningeal metastasis, and brain MRI suggests pia enhancement;\n7. The function of major organs was good, which was confirmed by the following laboratory tests during the screening period:\n\n   Platelet count ≥80\\*10\\^9\u002FL\n\n   Hemoglobin ≥8g\u002FL\n\n   Neutrophil count ≥1.5\\*10\\^9\u002FL\n\n   Serum creatinine ≤1.5\\*ULN\n\n   ALT and AST≤ 3\\*ULN (if liver metastases are present, ALT and AST≤5\\*ULN)\n\n   Serum total bilirubin ≤1.5\\*ULN\n\n   International Standardized ratio (INR) and Activated partial thromboplastin time (APTT) ≤1.5\\*ULN\n8. NYHA cardiac function grade ≤II, no obvious abnormality in ECG, or no clinical significance according to the investigators;\n9. Voluntary compliance with the trial protocol during the study period and regular follow-up;\n10. For all women of childbearing age, fertile men or their spouses who did not plan to have children or donate sperm during the entire trial period until 6 months after the last dose, or who voluntarily took effective contraception, the blood\u002Furine pregnancy test results of female patients of childbearing age within 7 days before enrollment were negative.\n11. Subjects who have recovered from non-hematological toxicity from the last treatment (CTCAE≤ class 1, except for special conditions such as \"alopecia\") before first administration, and who the investigator determines that the corresponding AE does not pose a safety risk.\n\nExclusion Criteria:\n\n1. Pregnant or lactating women;\n2. Patients with acute and chronic infections, or with other serious diseases at the same time, were judged not suitable for this study;\n3. Other malignant tumors within 5 years (except the following cases: cured skin basal cell carcinoma, cervical carcinoma in situ, thyroid papillary carcinoma; A second primary cancer that has been eradicated and has not recurred within five years; Both primary cancers are expected to benefit from this study. Investigators have identified the primary tumor source of the metastases);\n4. Mental illness or mental disorder, poor compliance can not cooperate with and describe treatment response;\n5. There are serious organic diseases or major organ failure, such as decompensated heart and lung failure, which can not tolerate treatment;\n6. Patients with bleeding tendency;\n7. Patients who have received organ transplants;\n8. Patients taking adrenal corticosteroids or immunosuppressants for a long time;\n9. Intracranial hemorrhage unrelated to tumor disease;\n10. Patients with central nervous system complications requiring urgent treatment;\n11. Test group: subjects who could not collect CSF;\n12. The subject has a history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases;\n13. Active viral hepatitis B (HBsAg positive with HBV DNA≥500 IU\u002FmL) or hepatitis C. Among hepatitis C antibody positive subjects, only those whose polymerase chain reaction showed negative HCV RNA were eligible for enrollment (chronic hepatitis B or chronic hepatitis C patients with stable disease receiving standard antiviral therapy were eligible for enrollment);\n14. The subject has a serious cardiovascular clinical disease or symptom, including:\n\n    Congestive heart failure\n\n    History of unstable angina;\n\n    myocardial infarction within the past six months;\n\n    Clinically significant malignant arrhythmias (except atrial fibrillation and paroxysmal supraventricular tachycardia);\n\n    Subjects had clinically significant prolonged QTcF\n\n    High blood pressure that is not well controlled;\n15. The researcher believes that the patient has other conditions that are not suitable for participating in this study.",{"count":238,"type":21},37,[240],"PHASE4","This is a prospective, multicenter, randomized controlled, open-label investigator-initiated clinical study to evaluate the clinical efficacy and quality of life of intrathecal chemotherapy through Ommaya reservoir in combination with systematic chemotherapy versus systemic chemotherapy alone in patients with Her-2 negative breast cancer with leptomeningeal metastasis.",[243,30],"HER2-negative Breast Cancer","2025-11-20",{"date":246,"type":35},"2025-11-25",{"date":248,"type":35},"2024-01-05",{"date":250,"type":21},"2027-01-01",{"name":252,"class":42},"Fudan University",{"id":254,"slug":255,"hasResults":11,"nctId":256,"briefTitle":257,"officialTitle":258,"acronym":259,"eligibilityCriteria":260,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":261,"targetDuration":4,"studyType":22,"phases":262,"briefSummary":263,"conditions":264,"keywords":267,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":273,"lastUpdatePostDateStruct":274,"startDateStruct":276,"completionDateStruct":278,"leadSponsor":280,"locationsCount":282},"100500747","phase-2-capecitabine-tucatinib-and-intrathecal-trastuzumab-for-breast-cancer-patients-with-leptomeningeal-disease-100500747","NCT05800275","Capecitabine, Tucatinib, and Intrathecal Trastuzumab for Breast Cancer Patients With Leptomeningeal Disease","Multicentric Single Arm Phase II Study Evaluating the Efficacy of Association of Tucatinib, Capecitabine and Intra-CSF Trastuzumab in HER2 Amplified Breast Cancer Patients With Leptomeningeal Metastases","ETIC-LM","Inclusion Criteria:\n\n1. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;\n2. Patients ≥18 years old;\n3. Histologically confirmed metastatic breast cancer;\n4. Histologically confirmed HER2 positive breast cancer, with HER2 positive defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology; Note: HER2 testing should be performed preferably metastatic site; any estrogen and progesterone (ER\u002FPR) status is allowed;\n5. Proven leptomeningeal progression defined by linear leptomeningeal metastases on magnetic resonance imaging (MRI) or the presence of breast cancer cells in CSF (obtained within 28 days before inclusion );\n6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2;\n7. Life expectancy ≥2 months;\n8. Stable dose of steroids for at least 5 days prior to registration;\n9. If symptomatic brain or leptomeningeal metastasis, local treatment (surgery, radiation therapy) is allowed until 2 weeks before inclusion but should have been completed no more than 8 weeks before inclusion and with no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator;\n10. Adequate hematological function within 14 days before inclusion: Absolute neutrophil count (ANC) ≥1.5 x 10⁹\u002FL; platelets count ≥100 x 10⁹\u002FL; and hemoglobin ≥9.0 g\u002FdL;\n11. Adequate liver function within 14 days before inclusion: total bilirubin ≤1.5 ULN (unless documented Gilbert's syndrome); AST and ALT ≤2.5 ULN (≤5 ULN in the presence of liver metastases);\n12. Normal renal function within 14 days before inclusion: estimated creatinine clearance ≥60 mL\u002Fmin according to the Cockcroft-Gault formula;\n13. Adequate cardiac function:\n\n    * 12 Lead electrocardiograms (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention\n    * QT\u002FQTc interval ≤470 msec for woman and ≤450 msec for men (mean of replicate values, correction per institutional standard) on the ECG at the screening visit and a normal kaliemia\n    * Left ventricular ejection fraction (LVEF) ≥55%\n    * No history of Torsades de Pointes or other symptomatic QTc abnormality\n14. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National cancer institute-Common terminology criteria for adverse events (NCI-CTCAE) version 5.0 grade 1 or 0 to baseline (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion);\n15. Women of childbearing potential must have a negative pregnancy test (blood or urine test) within 14 days prior to inclusion;\n16. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 7 months after completing treatment\u002Ftherapy. Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive;\n17. Patients affiliated to the social security system (or equivalent);\n18. Patient must be willing and able to comply with the protocol for the duration of the trial including scheduled visits, treatment plan, laboratory tests, and examinations including follow-up.\n\nExclusion Criteria:\n\n1. Used of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment. Use of sensitive CYP3A substrates should be avoided one week before enrollment and during study treatment;\n2. Previous treatment with Tucatinib or Capecitabine;\n3. Severe leukopenia, neutropenia, or thrombocytopena, severe hepatic impairment, severe renal impairment (creatinine clearance below 30mL\u002Fmin)\n4. Recent or concomitant treatment with brivudine ;\n5. Any antiplatelet or curative anticoagulant treatment for blood coagulation disorders;\n6. Severe pre-existing cerebrovascular dysfunction or pathology such as stroke and intra-cerebral hematoma or uncontrolled intracerebral hypertension induced by brain metastasis;\n7. Ventriculoperitoneal or atrial shunt, except if the valve is equipped with an on-off device and that the patient's condition allows for to remain in the off position for 6 hours after each injection of trastuzumab;\n8. Known history of testing positive for HIV or known acquired immunodeficiency syndrome;\n9. Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease;\n10. Uncontrolled hypertension;\n11. Uncontrolled infection;\n12. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy;\n13. Pregnant or breast-feeding women;\n14. Known prior severe hypersensitivity to tucatinib or compounds chemically or\u002Fand biologically similar or any component in its formulation;\n15. Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients in its formulation;\n16. Known prior severe hypersensitivity to capecitabine or to any of the excipients or fluorouracil;\n17. Known complete dihydropyrimidine dehydrogenase (DPD) deficiency (if applicable);\n18. Inability to swallow tablets or significant gastrointestinal disease which would preclude the adequate oral absorption of medications;\n19. Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 5 years;\n20. Person deprived of their liberty or under protective custody or guardianship;\n21. Participation in another therapeutic trial within the 30 days prior to treatment initiation;\n22. Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment, are not eligible. Patients unwilling or unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.",{"count":81,"type":21},[54],"The goal of this clinical trial is to evaluate the efficacy of tucatinib and capecitabine in combination with intrathecal trastuzumab on overall survival rate at 12 months in HER2-positive metastatic breast cancer (MBC) patients with proven leptomeningeal evolution and requiring intrathecal therapy.",[30,265,266],"Leptomeningeal Disease","HER2-positive Metastatic Breast Cancer",[268,265,269,30,270,271,272,266],"Intrathecal injection","Breast Cancer Metastatic","Intrathecal trastuzumab","Capecitabine","Tucatinib","2025-11-14",{"date":275,"type":35},"2025-11-18",{"date":277,"type":35},"2023-12-18",{"date":279,"type":21},"2027-06",{"name":281,"class":42},"UNICANCER",11,{"id":284,"slug":285,"hasResults":11,"nctId":286,"briefTitle":287,"officialTitle":288,"acronym":4,"eligibilityCriteria":289,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":290,"targetDuration":4,"studyType":22,"phases":292,"briefSummary":293,"conditions":294,"keywords":295,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":297,"lastUpdatePostDateStruct":298,"startDateStruct":300,"completionDateStruct":302,"leadSponsor":304,"locationsCount":43},"100539484","intra-pemetrexed-plus-third-generation-small-molecule-tki-drugs-eg-osimertinib-versus-third-generation-small-molecule-tki-drugs-alone-for-leptomeningeal-metastasis-from-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-100539484","NCT06304441","Intra-pemetrexed Plus Third-generation Small Molecule TKI Drugs (e.g. 'Osimertinib') Versus Third-generation Small Molecule TKI Drugs Alone for Leptomeningeal Metastasis From Epidermal Growth Factor Receptor Mutation-Positive Non-Small-cell Lung Cancer","A Clinical Trial of Intra-pemetrexed Plus Third-generation Small Molecule TKI Drugs (e.g. 'Osimertinib') Versus Third-generation Small Molecule TKI Drugs Alone for Leptomeningeal Metastasis From Epidermal Growth Factor Receptor Mutation-Positive Non-Small-cell Lung Cancer","Inclusion Criteria:\n\n1. Male or female aged between 18 and 75 years.\n2. Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del).\n3. Confirmed diagnosis of leptomeningeal metastasis according to ESMO\u002FEANO guidelines.\n4. Normal liver and kidney function; WBC≥4000\u002Fmm3, Plt≥100000\u002Fmm3.\n5. No history of severe nervous system disease.\n6. No severe dyscrasia.\n\nExclusion Criteria:\n\n1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.\n2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.\n3. Patients with poor compliance or other reasons that were unsuitable for this study.",{"count":291,"type":21},100,[83],"Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases. Pemetrexed is one of the first-line chemotherapeutic agents for non-squamous non-small cell lung cancer (NSCLC). Since 2017, intrathecal pemetrexed has shown good efficacy for patients with leptomeningeal metastases from NSCLC. It has been recommended as the preferred drug for intrathecal chemotherapy by the Chinese Society of Clinical Oncology (CSCO) guidelines. Tyrosine kinase inhibitors (TKIs) play a promising role in the treatment of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. Due to its small molecule properties, it can effectively penetrate the central nervous system barrier and deliver an effective antitumor effect. An international multi-center clinical study published in 2019 confirmed that double-dose of osimertinib showed significant improvement in leptomeningeal metastases from NSCLC with EGFR exon 19 deletion or exon 21 L858R\u002FT790M mutation. It makes TKIs the mainstay of treatment for patients with EGFR-mutant NSCLC with leptomeningeal metastases. However, whether third-generation small molecule TKI drugs (e.g. 'osimertinib') combined with intrathecal pemetrexed could benefit patients with LM from EGFR- mutant NSCLC remains undetermined.",[30],[215,216,217,296,218,219],"Third-generation small molecule TKI drugs","2025-09-24",{"date":299,"type":35},"2025-09-29",{"date":301,"type":35},"2024-04-18",{"date":303,"type":21},"2026-09",{"name":229,"class":42},{"id":306,"slug":307,"hasResults":11,"nctId":308,"briefTitle":309,"officialTitle":310,"acronym":4,"eligibilityCriteria":311,"healthyVolunteers":11,"sex":312,"minAge":17,"maxAge":18,"enrollmentInfo":313,"targetDuration":4,"studyType":22,"phases":315,"briefSummary":316,"conditions":317,"keywords":320,"overallStatus":62,"whyStopped":4,"lastUpdateSubmitDate":323,"lastUpdatePostDateStruct":324,"startDateStruct":326,"completionDateStruct":328,"leadSponsor":330,"locationsCount":4},"100606622","phase-1-a-two-cohort-study-of-shr-a1811-in-the-treatment-of-her2-positive-breast-cancer-with-brain-metastases-100606622","NCT07177950","A Two-cohort Study of SHR-A1811 in the Treatment of HER2-positive Breast Cancer With Brain Metastases","A Two-cohort Study of SHR-A1811 in the Treatment of HER2-positive Breast Cancer With Brain Metastases, With or Without Leptomeningeal Metastases.","Inclusion Criteria:\n\n1. Women aged 18-75 years (inclusive).\n2. Histologically or cytologically confirmed HER2-positive advanced breast cancer (IHC 3+, or IHC 2+ with ISH amplification).\n3. Radiologically documented brain metastases, with or without baseline leptomeningeal disease:\n\n   * Cohort A (leptomeningeal metastasis cohort): leptomeningeal involvement demonstrated by contrast-enhanced MRI or positive cerebrospinal fluid (CSF) cytology.\n   * Cohort B (no leptomeningeal metastasis cohort): ≥1 measurable intracranial lesion; either CNS-naïve or progressive after prior local therapy.\n4. Anticipated life expectancy \\>12 weeks.\n5. ECOG performance status 0-2.\n6. Adequate organ function as defined by the following laboratory criteria:\n\n   1. Hematologic: absolute neutrophil count (ANC) ≥1.5 × 10⁹\u002FL, platelet count (PLT) ≥100 × 10⁹\u002FL, hemoglobin (HGB) ≥90 g\u002FL.\n   2. Hepatic: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN) (≤5 × ULN in patients with liver metastases); total serum bilirubin (TBIL) ≤1.5 × ULN; serum albumin ≥30 g\u002FL.\n   3. Renal: serum creatinine (Cr) ≤1.5 × ULN or calculated creatinine clearance ≥50 mL\u002Fmin using the Cockcroft-Gault formula.\n   4. Coagulation: prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5 × ULN.\n   5. Cardiac: left ventricular ejection fraction (LVEF) ≥50%.\n7. Negative serum pregnancy test; women of childbearing potential must use a highly effective contraceptive method from study initiation until at least 6 months after the last dose of study medication.\n8. Voluntary participation with written informed consent obtained prior to any study-related procedures.\n\nExclusion Criteria:\n\n1. Cohort A participants must be excluded if any of the following apply:\n\n   1. Cerebrospinal fluid (CSF) circulation obstruction that cannot be adequately controlled by therapeutic measures.\n   2. MRI evidence of nodular leptomeningeal (LM) disease in the setting of negative CSF cytology.\n   3. Active central nervous system (CNS) infection.\n   4. Clinically significant coagulopathy.\n2. Cohort B participants must be excluded if leptomeningeal metastasis is documented, defined as either: radiographic evidence of leptomeningeal involvement, or positive CSF cytology, or unequivocal clinical signs or symptoms attributable to leptomeningeal disease.\n3. Presence of clinically significant third-space fluid accumulation (e.g., massive pleural or peritoneal effusion) that cannot be adequately controlled by drainage or other interventions.\n4. Known hypersensitivity to any study drug or its excipients, or to any prior humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab).\n5. Prior or current exposure to antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, including but not limited to fam-trastuzumab deruxtecan (DS-8201a).\n6. Clinically significant cardiovascular disease, including but not limited to: severe or unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association class ≥ II), clinically relevant supraventricular or ventricular arrhythmias requiring therapy or intervention, myocardial infarction within 6 months prior to first study dose, or cerebrovascular accident (including transient ischemic attack).\n7. Participants known or suspected to interstitial lung disease.\n8. Concurrent participation in any other interventional drug clinical trial.\n9. Refusal to comply with protocol-mandated follow-up.\n10. Presence of any additional severe physical or psychiatric disorder, or any laboratory abnormality that, in the investigator's judgment, could increase the subject's risk, confound study results, or render the patient unsuitable for enrollment.","FEMALE",{"count":314,"type":21},51,[24,54],"This is a multi-center, open-label, two-cohort study. The purpose of this study is to evaluate the safety, tolerability and efficacy of SHR-A1811 in the treatment of HER2-positive breast cancer with brain and leptomeningeal metastases, and the efficacy and safety of SHR-A1811 in the treatment of HER2-positive breast cancer with brain but without leptomeningeal metastases.",[318,319,30],"Breast Cancer","Brain Metastases",[321,322],"HER2-positive breast cancer","SHR-A1811","2025-09-10",{"date":325,"type":35},"2025-09-17",{"date":327,"type":21},"2025-09-30",{"date":329,"type":21},"2029-09-30",{"name":331,"class":42},"Peking University Cancer Hospital & Institute",{"id":333,"slug":334,"hasResults":11,"nctId":335,"briefTitle":336,"officialTitle":337,"acronym":338,"eligibilityCriteria":339,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":340,"targetDuration":4,"studyType":22,"phases":342,"briefSummary":343,"conditions":344,"keywords":345,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":356,"lastUpdatePostDateStruct":357,"startDateStruct":359,"completionDateStruct":361,"leadSponsor":363,"locationsCount":43},"100600539","phase-1-multiple-dose-intraventricular-administration-of-rhenium-186-nanoliposome-for-leptomeningeal-metastases-100600539","NCT07098806","Multiple Dose Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases","A Multicenter Phase 1 Study to Determine the Safety and Efficacy of Multiple Doses at Defined Intervals of Rhenium (186Re) Obisbemeda (Rhenium-186 NanoLiposome, 186RNL) Administered Via Intraventricular Catheter for Any Primary Solid Tumor Cancer With Leptomeningeal Metastases","CA2024-LM-001","Inclusion Criteria:\n\n1. At least 18 years of age.\n2. Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.\n3. Documented LM from any primary solid tumor cancer per EANO-ESMO Clinical Practice Guidelines (Types I or IIA-C).\n4. Karnofsky performance status of 70 to 100.\n5. Acceptable liver function:\n\n   1. Bilirubin ≤ 1.5 times the upper limit of normal.\n   2. AST (SGOT) and ALT (SGPT) ≤ 3.0 times the upper limit of normal for subjects with normal liver.\n   3. AST (SGOT) and ALT (SGPT) ≤ 5.0 times the upper limit of normal for subjects with liver metastasis.\n6. Acceptable renal function:\n\n   a. Creatinine clearance greater than or equal to 60 mL\u002Fmin (using the Cockcroft-Gault Equation).\n7. Acceptable hematologic functioning (without hematologic support):\n\n   1. ANC ≥ 1000 cells μL.\n   2. Platelet count ≥ 75,000\u002FμL.\n   3. Hemoglobin ≥ 9.0 g\u002FdL.\n8. All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.\n9. Normal CSF flow and distribution by an accepted CSF flow study (e.g., 111Indium-DTPA or acceptable substitute) before first treatment with the study drug, based on study imaging interpretation and clinical correlation.\n10. Corticosteroids are permitted as clinically indicated.\n\nExclusion Criteria:\n\n1. The subject has not recovered to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade ≤1 from adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study, at time of study registration.\n\n   a. Prior AEs due to alopecia, anemia, neutropenia, and lymphopenia are not required to be recovered to Grade ≤1 prior to study registration, assuming other inclusion criteria are satisfied.\n2. Contraindications to the placement of an intraventricular catheter (i.e., Ommaya reservoir.)\n3. Presence of or need for a Ventriculo-peritoneal or ventriculo-atrial shunt.\n4. Females of childbearing potential who are pregnant, breastfeeding, or may possibly be pregnant, without a negative serum pregnancy test (see inclusion criteria).\n5. Serious intercurrent illnesses, which could interfere with the planned treatment schedule.\n6. Patients who had any therapeutic radiation dose to the whole brain regardless of when the radiation treatment was delivered, except:\n\n   1. Prior radiation dose to the spinal cord and\u002For cauda equina is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to the spinal cord and\u002For cauda equina using α\u002Fβ ratio of 3 and if prior radiotherapy has been \\> 14 days and ≤ 6 months, or was ≤45 Gy to the spinal cord and\u002For cauda equina using α\u002Fβ ratio of 3 and if prior radiotherapy has been \\> 6 months.\n   2. Prior stereotactic radiosurgery (SRS) to the brain or partial brain radiotherapy is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to brainstem and\u002For optic structures (optic nerves, optic chiasm) using α\u002Fβ ratio of 3 and if prior radiotherapy has been \\> 14 days and ≤ 6 months, or was ≤ 45 Gy to the brainstem and\u002For optic structures (optic nerves, optic chiasm) using α\u002Fβ ratio of 3 and if prior radiotherapy has been \\> 6 months.\n7. Prior or concurrent therapy:\n\n   a. Intrathecally delivered therapy: i. Concurrent: Concurrent intrathecal therapy. ii. Prior: Intrathecal therapy given less than 14 days before study registration.\n\n   b. Systemically delivered therapy: i. Concurrent: Systemically delivered therapy UNLESS LM develops while on systemically delivered therapy AND the systemically delivered therapy is NOT associated with more than grade 1 myelosuppression.\n\n   ii. Prior: Systemically delivered therapy given less than 28 days before study registration.\n8. Projected survival of less than 60 days.",{"count":341,"type":21},24,[24],"This is an open-label, multicenter, Phase 1 study to determine the safety and efficacy of multiple doses at defined intervals of rhenium (186Re) obisbemeda (rhenium-186 nanoliposome, 186RNL) administered via intraventricular catheter for any primary solid tumor cancer with leptomeningeal metastases to identify an MTD\u002FMFD for a given dose, interval duration, and number of doses.",[30],[346,347,348,349,350,351,352,353,354,355],"Neoplastic Processes Neoplasms","Neoplasms","Pathologic Processes","Meningeal Neoplasms","Central Nervous System Neoplasms","Nervous System Neoplasms","Neoplasms by Site","Nervous System Diseases","Neoplasm Metastasis","Meningeal Carcinomatosis","2025-07-29",{"date":358,"type":35},"2025-08-01",{"date":360,"type":35},"2025-07-02",{"date":362,"type":21},"2031-10-02",{"name":364,"class":365},"Plus Therapeutics","INDUSTRY",{"id":367,"slug":368,"hasResults":11,"nctId":369,"briefTitle":370,"officialTitle":371,"acronym":4,"eligibilityCriteria":372,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":373,"targetDuration":4,"studyType":22,"phases":375,"briefSummary":376,"conditions":377,"keywords":380,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":383,"lastUpdatePostDateStruct":384,"startDateStruct":385,"completionDateStruct":387,"leadSponsor":389,"locationsCount":43},"100600031","phase-4-firmonertinib-combined-with-intrathecal-injection-for-the-treatment-of-egfr-mutant-nsclc-with-leptomeningeal-metastases-100600031","NCT07092202","Firmonertinib Combined With Intrathecal Injection for the Treatment of EGFR Mutant NSCLC With Leptomeningeal Metastases","Exploratory Clinical Study on Dynamic Monitoring of cfDNA in Cerebrospinal Fluid and Peripheral Blood Using High-dose Firmonertinib Combined With Intrathecal Injection of Pemetrexed for the Treatment of EGFR Mutant NSCLC With Leptomeningeal Metastases","Inclusion Criteria:\n\n* Obtain an informed consent form signed by the patient or their legal representative;\n* Age greater than or equal to 18 years old;\n* According to the 9th edition TNM staging of lung cancer by the International Association for the Study of Lung Cancer and the Joint Committee on Cancer Staging in the United States, metastatic (stage IV) NSCLC with histological or cytological confirmation;\n* Confirmed by histological or cytological specimens tested in the central laboratory to have EGFR exon 19 deletion mutation (19DEL) or exon 21 L858R point mutation (L858R), which can exist alone or in combination;\n* ECOG physical condition score is 0-3 points, with an expected life expectancy of ≥ 12 weeks;\n* According to the criteria for evaluating the efficacy of solid tumors (RECIST 1.1), there should be at least one measurable lesion;\n* According to the \"EANO-ESMO\" diagnostic criteria for meningeal metastasis (Type I: positive cerebrospinal fluid cytology or biopsy; Type II: limited to typical clinical symptoms and neuroimaging findings), for clinical judgment. Patients with leptomeningeal metastases who can be included in the study are type I patients and type II patients with EGFR mutations in cerebrospinal fluid ctDNA; merged brain parenchymal metastases can also be included in the study;\n* Progress in first-line treatment with first and second-generation EGFR-TKI;\n* Progress in first-line conventional dose treatment with third-generation EGFR-TKI;\n* The subject must accept and be able to cooperate with the lumbar puncture procedure, and confirm that there are no contraindications to chemotherapy or lumbar puncture;\n* At least 4 weeks before treatment, all extracranial symptoms must be stable, and there must be no CNS complications requiring emergency neurosurgical intervention.\n\nExclusion Criteria:\n\n* Squamous cell carcinoma of the lung;\n* Known history of hypersensitivity reactions to drugs with or without active excipients or similar structures or categories to the investigational drug for famotinib\u002Fpemetrexed;\n* Confirmed EGFR exon 20 insertion mutation;\n* At the beginning of drug treatment, if the toxicity associated with previous anti-tumor therapy has not recovered to ≤ CTCAE Grade 1, except for peripheral neurotoxicity caused by hair loss or chemotherapy ≤ CTCAE Grade 2;\n* Excluding skin basal cell carcinoma, cervical carcinoma in situ, and ductal carcinoma of the breast that have been effectively controlled and have been diagnosed with other malignant tumors or have a history of other malignant tumors in the past 5 years;\n* Patients who are deemed ineligible by researchers to participate in this study, such as those who are highly likely to be unable to comply with the study protocol, constraints, and requirements, or other situations determined by the researcher at their discretion;\n* Pregnancy or lactation.",{"count":374,"type":21},40,[240],"Leptomeningeal metastases (LM) are a relatively rare site of metastasis in advanced non-small cell lung cancer (NSCLC), and LM patients have a poor prognosis. Numerous retrospective studies have reported that high-dose Firmonertinib can also effectively increase patient prognosis and have tolerable side effects, but there is a lack of prospective studies to confirm this. In addition, there are currently no good biomarkers for monitoring the efficacy of LM treatment. cfDNA testing can be used for early cancer screening, monitoring tumor progression, evaluating treatment response, and discovering drug resistance mechanisms. Due to the influence of the blood-brain barrier, the level of cfDNA in the plasma of LM patients is often very low, and the detection of cfDNA in cerebrospinal fluid (CSF) is more advantageous. Therefore, exploring the dynamic monitoring of LM treatment efficacy using CSF cfDNA is of great significance for improving patient prognosis. Based on this, the applicant intends to conduct a prospective, multicenter, single-arm, post-market exploratory clinical trial on the treatment methods and efficacy monitoring of NSCLC-LM patients. The aim was to explore whether cfDNA has the potential to become a biomarker for LM efficacy monitoring and to validate the efficacy and safety of high-dose fumatinib combined with intrathecal injection in the treatment of NSCLC-LM patients.",[30,27,378,379],"Intrathecal Chemotherapy","Tyrosine Kinase Inhibitor",[215,27,378,381,379,382],"Firmonertinib","cfDNA","2025-07-27",{"date":356,"type":35},{"date":386,"type":35},"2025-04-15",{"date":388,"type":21},"2027-11-01",{"name":390,"class":42},"Union Hospital, Tongji Medical College, Huazhong University of Science and Technology",{"id":392,"slug":393,"hasResults":11,"nctId":394,"briefTitle":395,"officialTitle":396,"acronym":4,"eligibilityCriteria":397,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":398,"targetDuration":400,"studyType":401,"phases":4,"briefSummary":402,"conditions":403,"keywords":4,"overallStatus":62,"whyStopped":4,"lastUpdateSubmitDate":405,"lastUpdatePostDateStruct":406,"startDateStruct":408,"completionDateStruct":410,"leadSponsor":411,"locationsCount":413},"100593388","ai-based-ultrasound-prediction-model-for-intracranial-pressure-and-prognosis-in-lung-cancer-patients-with-leptomeningeal-metastasis-a-dual-center-study-100593388","NCT07005791","AI-Based Ultrasound Prediction Model for Intracranial Pressure and Prognosis in Lung Cancer Patients With Leptomeningeal Metastasis: A Dual-Center Study","基于人工智能的视神经鞘超声视频构建肺癌软脑膜转移患者颅内压预测模型及多模态临床预后模型的双中心临床研究","Inclusion Criteria:\n\n1- Age: Participants must be aged 18 years or older. 2、Diagnosis: Patients must have a histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) with clinically or pathologically confirmed leptomeningeal metastases (LM), and at least one measurable lesion.\n\n3、Lumbar Puncture and Intrathecal Chemotherapy: Patients must have undergone lumbar puncture and intrathecal chemotherapy in the study center.\n\n4、ECOG Performance Status: Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3.\n\n5、Blood Tests: Neutrophil count ≥ 1.5 × 10⁹\u002FL. Hemoglobin ≥ 9 g\u002FdL. Platelet count ≥ 100 × 10⁹\u002FL. 6、Biochemical Tests: Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). AST (aspartate aminotransferase) and ALT (alanine aminotransferase) \\< 1.5 times ULN.\n\nCreatinine clearance ≥ 60 ml\u002Fmin. 7、No Significant Bleeding or Thrombosis: Patients must not have significant bleeding symptoms, bleeding disorders, or active thrombosis.\n\n8、Reproductive Health: Women of childbearing age must use appropriate contraception and have a negative pregnancy test prior to enrollment.\n\n9、Informed Consent: All patients must have signed the informed consent form and be willing to comply with the study procedures and follow-up schedule.\n\nExclusion Criteria:\n\n* 1、Histological Type: Patients with squamous cell carcinoma or small cell lung cancer are excluded.\n\n  2、Recent Radiotherapy: Patients who have received local radiotherapy for intracranial lesions within the past two weeks are excluded.\n\n  3、ECOG Performance Status: Patients with an ECOG performance score greater than 3 are excluded.\n\n  4、Uncontrolled Seizures: Patients with uncontrolled seizures are excluded. 5、Other Tumor History: Patients with a current or past history of other tumors are excluded.\n\n  6、Bleeding or Thrombotic Disorders: Patients with known hereditary or acquired bleeding or thrombotic tendencies (e.g., hemophilia, coagulation disorders, thrombocytopenia) or with abnormal coagulation function (INR \\> 2.0, PT \\> 16s) are excluded. Those on thrombolytic or anticoagulant therapy are also excluded, except for patients on preventive doses of low-dose aspirin or low-molecular-weight heparin.\n\n  7、Recent Trauma or Surgery: Patients with a history of severe trauma or surgery within the last month, or significant bleeding events within the past three months, are excluded.\n\n  8、Severe Organ Dysfunction: Patients with severe hepatic or renal dysfunction, HIV infection, HCV infection, asthma, or uncontrolled cerebrovascular disease are excluded.\n\n  9、Pregnancy and Breastfeeding: Pregnant or breastfeeding women are excluded. Women of childbearing age must test negative for pregnancy within seven days prior to enrollment.\n\n  10、Thrombotic Events: Patients with arterial or venous thrombotic events (e.g., stroke, transient ischemic attack, brain hemorrhage, deep vein thrombosis, or pulmonary embolism) within the past six months are excluded.\n\n  11、Safety Concerns: Any other conditions or factors that the investigator deems unsuitable for inclusion, including issues that might compromise the patient\\'s safety or compliance, will result in exclusion.",{"count":399,"type":21},142,"2 Years","OBSERVATIONAL","This study focuses on developing an innovative, artificial intelligence-based model using optic nerve sheath ultrasound videos to predict intracranial pressure in lung cancer patients with leptomeningeal metastasis. The study also aims to create a multimodal clinical prognosis model that can help improve patient outcomes. By analyzing ultrasound data from patients at two major medical centres, the research seeks to provide more accurate and early predictions of complications related to elevated intracranial pressure, ultimately improving treatment and management strategies for these patients.",[162,30,404],"Intracranial Pressure","2025-06-03",{"date":407,"type":35},"2025-06-05",{"date":409,"type":21},"2025-07-01",{"date":95,"type":21},{"name":412,"class":42},"The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School",2,{"id":415,"slug":416,"hasResults":11,"nctId":417,"briefTitle":418,"officialTitle":419,"acronym":4,"eligibilityCriteria":420,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":421,"targetDuration":4,"studyType":22,"phases":422,"briefSummary":423,"conditions":424,"keywords":425,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":429,"lastUpdatePostDateStruct":430,"startDateStruct":432,"completionDateStruct":434,"leadSponsor":436,"locationsCount":43},"100574653","phase-1-intrathecal-combination-of-programmed-death-1-pd-1cytotoxic-t-lymphocyte-associated-protein-4-ctla-4-bispecific-antibody-and-pemetrexed-for-leptomeningeal-metastasis-100574653","NCT06762080","Intrathecal Combination of Programmed Death-1 (PD-1)\u002FCytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Bispecific Antibody and Pemetrexed for Leptomeningeal Metastasis","Intrathecal Administration of PD-1\u002FCTLA-4 Bispecific Antibody Plus Pemetrexed in Patients With Leptomeningeal Metastasis From Solid Tumors: A Phase I\u002FII Study","Inclusion Criteria:\n\n1. Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.\n2. Male or female aged between 18 and 75 years; Normal liver and kidney function; WBC≥4000\u002Fmm3, Plt≥100000\u002Fmm3.\n3. No history of severe nervous system disease; No severe dyscrasia.\n\nExclusion Criteria:\n\n1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.\n2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.\n3. A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing \\>Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.\n4. The first month to treatment, as well as during induction and consolidation therapy, new drugs effective against leptomeningeal metastases were used, excluding those previously administered. These primarily included small molecule targeted therapies, such as EGFR-TKI\u002FALK-TKI drugs like Osimertinib and Lorlatinib.\n5. Patients with poor compliance or other reasons that were unsuitable for this study.",{"count":210,"type":21},[24,54],"Leptomeningeal metastasis, characterized by tumor cells infiltrating and proliferating in the subarachnoid space, represents a distinct pattern of central nervous system involvement and is a fatal complication of malignant tumors. This phase I\u002FII study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal Programmed Death-1 (PD-1)\u002FCytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) bispecific antibodies combined with pemetrexed in patients with leptomeningeal metastasis.",[30],[426,427,217,428,30],"Cadonilimab","PD-1\u002FCTLA-4","Intrathecal","2025-05-15",{"date":431,"type":35},"2025-05-20",{"date":433,"type":35},"2025-03-07",{"date":435,"type":21},"2026-06-01",{"name":229,"class":42},{"id":438,"slug":439,"hasResults":11,"nctId":440,"briefTitle":441,"officialTitle":442,"acronym":4,"eligibilityCriteria":443,"healthyVolunteers":11,"sex":16,"minAge":444,"maxAge":18,"enrollmentInfo":445,"targetDuration":4,"studyType":22,"phases":447,"briefSummary":448,"conditions":449,"keywords":451,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":429,"lastUpdatePostDateStruct":453,"startDateStruct":454,"completionDateStruct":456,"leadSponsor":458,"locationsCount":43},"100578301","phase-1-intrathecal-pd-1vegf-bispecific-antibody-plus-pemetrexed-for-leptomeningeal-metastasis-100578301","NCT06809517","Intrathecal PD-1\u002FVEGF Bispecific Antibody Plus Pemetrexed for Leptomeningeal Metastasis","A Phase I\u002FII Clinical Study of Intrathecal Combination Therapy With the PD-1\u002FVEGF Bispecific Antibody and Pemetrexed for Leptomeningeal Metastasis","Inclusion Criteria:\n\n1. Histologically or cytologically confirmed diagnosis of solid tumors;Cerebrospinal fluid cytopathology is positive.\n2. Male or female aged between 21 and 75 years; Normal liver and kidney function; WBC≥4000\u002Fmm3, Plt≥100000\u002Fmm3.\n3. No history of severe nervous system disease; No severe dyscrasia.\n\nExclusion Criteria:\n\n1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.\n2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.\n3. Obvious bleeding tendency; Patients with hemorrhage (NCI-CTCAE v5.0 greater than grade 2), coagulation disorder, hypertensive crisis, and severe arterial thrombosis.\n4. A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing \\>Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.\n5. The first month to treatment, as well as during induction and consolidation therapy, new drugs effective against leptomeningeal metastases were used, excluding those previously administered. These primarily included small molecule targeted therapies, such as EGFR-TKI\u002FALK-TKI drugs like Osimertinib and Lorlatinib.\n6. Patients with poor compliance or other reasons that were unsuitable for this study.","21 Years",{"count":446,"type":21},34,[24,54],"Leptomeningeal metastasis, characterized by tumor cells infiltrating and proliferating in the subarachnoid space, represents a distinct pattern of central nervous system involvement and is a fatal complication of malignant tumors.\n\nThis phase I\u002FII study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal PD-1\u002FVEGF bispecific antibody plus pemetrexed in patients with leptomeningeal metastasis.",[30,450],"Intrathecal Drug Delivery",[215,452,217],"PD-1\u002FVEGF Bispecific Antibody",{"date":431,"type":35},{"date":455,"type":35},"2025-03-18",{"date":457,"type":21},"2026-05-01",{"name":229,"class":42},{"id":460,"slug":461,"hasResults":11,"nctId":462,"briefTitle":463,"officialTitle":464,"acronym":4,"eligibilityCriteria":465,"healthyVolunteers":11,"sex":16,"minAge":444,"maxAge":18,"enrollmentInfo":466,"targetDuration":4,"studyType":22,"phases":467,"briefSummary":468,"conditions":469,"keywords":472,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":475,"lastUpdatePostDateStruct":476,"startDateStruct":478,"completionDateStruct":480,"leadSponsor":482,"locationsCount":413},"100578302","phase-1-intrathecal-dual-checkpoint-inhibitor-pd-1-and-ctla-4-in-combination-with-pemetrexed-for-leptomeningeal-metastasis-100578302","NCT06809530","Intrathecal Dual Checkpoint Inhibitor (PD-1 and CTLA-4) in Combination With Pemetrexed for Leptomeningeal Metastasis","Intrathecal Administration of Dual Checkpoint Inhibitor in Combination With Pemetrexed in Patients With Leptomeningeal Metastasis: a Phase I\u002FII Study","Inclusion Criteria:\n\n1. Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive.\n2. Male or female aged between 21 and 75 years; Normal liver and kidney function; WBC≥4000\u002Fmm3, Plt≥100000\u002Fmm3.\n3. No history of severe nervous system disease; No severe dyscrasia.\n\nExclusion Criteria:\n\n1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.\n2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.\n3. A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing \\>Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.\n4. Patients with poor compliance or other reasons that were unsuitable for this study.",{"count":446,"type":21},[24,54],"This phase I\u002FII study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal dual checkpoint inhibitor (targeting PD-1 and CTLA-4 with QL1706) in combination with pemetrexed in patients with leptomeningeal metastasis.",[30,217,29,470,471],"CTLA4","Solid Tumors",[215,473,474],"dual checkpoint inhibitor","pemetrexed","2025-05-14",{"date":477,"type":35},"2025-05-18",{"date":479,"type":35},"2025-03-17",{"date":481,"type":21},"2026-07-01",{"name":229,"class":42},{"id":484,"slug":485,"hasResults":11,"nctId":486,"briefTitle":487,"officialTitle":488,"acronym":489,"eligibilityCriteria":490,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":491,"targetDuration":4,"studyType":22,"phases":493,"briefSummary":494,"conditions":495,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":496,"lastUpdatePostDateStruct":497,"startDateStruct":499,"completionDateStruct":501,"leadSponsor":503,"locationsCount":413},"100496632","proton-cranio-spinal-irradiation-for-leptomeningeal-metastasis-100496632","NCT05746754","Proton Cranio-spinal Irradiation for Leptomeningeal Metastasis","Phase II Study of Proton Cranio-spinal Irradiation for Leptomeningeal Metastasis","CSI ProLong","Inclusion Criteria:\n\n* Metastasis to the leptomeningeal space (LM) surrounding the brain and\u002F or spinal cord\n* Metastasis verified by MRI or CSF cytology\n* Karnofsky \\>=60 (requiring some help, can take care of most personal requirements)\n* Adequate bone marrow function\n\n  * Haemoglobin \\> 5 mmol\u002Fl\n  * Absolute neutrophil count \\>1 10\\^9\u002Fl\n  * Platelet count \\> 100 10\\^9\u002Fl\n* Patient consent\n* Female subjects must either be of non-reproductive potential ( ≥ 60 years old, or with no menses for \\>1 year without an alternative medical cause\\], OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a pregnancy test within 2 weeks prior to starting treatment.\n* Patient at reproductive potential must agree to practice an effective contraceptive method.\n\nExclusion Criteria:\n\n* • Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances (Yang)\n\n  * Patient with multiple, serious major neurologic deficits per physician\u002Finvestigator assessment including encephalopathy\n  * Patient with extensive systemic disease and without reasonable systemic treatment options\n  * Patient who is unable to undergo MRI brain and spine with gadolinium contrast\n  * Pregnant or lactating women.",{"count":492,"type":21},50,[83],"Leptomeningeal metastasis is a rare but serious complication to cancer, with a grave prognosis. No efficient treatment exists.\n\nRecent data suggest that craniospinal radiotherapy lead to superior survival and CNS control compared to focal photon radiotherapy. We want to offer Danish patients the new treatment, but within a protocol, as this is new data with an new treatment principle",[30],"2025-04-02",{"date":498,"type":35},"2025-04-06",{"date":500,"type":35},"2023-11-01",{"date":502,"type":21},"2031-04-01",{"name":504,"class":42},"University of Aarhus",{"id":506,"slug":507,"hasResults":11,"nctId":508,"briefTitle":509,"officialTitle":510,"acronym":4,"eligibilityCriteria":511,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":512,"targetDuration":4,"studyType":22,"phases":514,"briefSummary":515,"conditions":516,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":517,"lastUpdatePostDateStruct":518,"startDateStruct":520,"completionDateStruct":522,"leadSponsor":524,"locationsCount":43},"100585396","phase-2-a-study-of-the-safety-and-efficacy-of-pemetrexed-combined-with-nivolumab-via-intraventricular-injection-for-the-treatment-of-refractory-non-squamous-non-small-cell-lung-cancer-with-leptomeningeal-metastases-100585396","NCT06901817","A Study of the Safety and Efficacy of Pemetrexed Combined with Nivolumab Via Intraventricular Injection for the Treatment of Refractory Non-squamous Non-small Cell Lung Cancer with Leptomeningeal Metastases","A Multicenter, Prospective, Phase II Study on Intraventricular Injection of Pemetrexed Combined with Nivolumab Via an Ommaya Reservoir for the Treatment of Refractory Non-squamous Non-small Cell Lung Cancer (NSCLC) with Leptomeningeal Metastases in Previously Treated Patients","Inclusion Criteria:\n\n* Patients who sign the informed consent form and are willing to complete the study according to the protocol;\n* Patients must have radiographic and\u002For cerebrospinal fluid cytology evidence of leptomeningeal disease (LMD). The diagnosis of non-small cell lung cancer must be confirmed, based on histological and\u002For cytological diagnosis.\n* Patients must have an ECOG performance status score of ≤ 2.\n* Patients may use steroids to control symptoms related to the central nervous system, but the dose must be ≤ 4 mg of dexamethasone (or equivalent dose) within 24 hours. The patient's neurological symptoms should remain stable for at least 7 days, or they are reducing the dose of steroids. Physiological replacement doses for adrenal insufficiency are allowed.\n* Patients who have received brain and\u002For spinal radiotherapy, including whole-brain radiation, stereotactic radiosurgery, or SBRT, can be enrolled, but must have completed radiation therapy at least 7 days before starting treatment.\n* Patients who have received approved systemic treatments may continue the systemic treatment chosen by the researcher. Concurrent use of other drugs for intrathecal treatment is not allowed. For patients who have received other systemic treatments, the minimum washout periods are as follows:\n\n  1. Patients who have received intrathecal treatment must have had their last treatment at least 7 days before starting the study treatment.\n  2. Patients who have received systemic chemotherapy must have had their last treatment at least 14 days before starting the study treatment.\n  3. Patients who have received approved systemic immunotherapy (such as anti-PD-1, anti-CTLA4) must have had their last treatment at least 2 weeks before starting the study treatment.\n  4. Patients who have received any other investigational drugs must have had their last treatment at least 14 days before starting the study treatment.\n* Age ≥ 18 years.\n* Able to provide written informed consent, including compliance with the requirements and restrictions listed in the consent form.\n* Patients must have the organ and bone marrow function defined in Table 1 below.\n* No contraindications to the installation of an Ommaya reservoir.\n* Criteria for refractory leptomeningeal metastasis:\n\n  1. Failed first- or second-generation TKI treatment, T790M mutation-negative;\n  2. Failed third-generation TKI treatment;\n  3. EGFR gene mutation-negative, failed first-line treatment.\n\nExclusion Criteria:\n\n* Patients who require a VP shunt due to increased intracranial pressure.\n* Patients must not have active autoimmune diseases requiring systemic treatment in the past two years (i.e., using disease-modifying agents, corticosteroids, or immunosuppressive drugs). Alternative therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered forms of systemic treatment.\n* Subjects who need systemic treatment within 14 days prior to administration of the study drug, including the use of corticosteroids (\\>4 mg daily dexamethasone equivalent dose) or other immunosuppressive drugs. Inhaled or topical steroids and adrenal replacement therapy at a daily replacement dose \\>10 mg prednisone equivalent are allowed in the absence of active autoimmune diseases.\n* Patients who have previously received PD-1 and\u002For anti-CTLA-4 therapy are eligible, unless they are experiencing \\> grade 2 side effects from such treatments. Ongoing physiological replacement doses for adrenal and thyroid insufficiency are allowed in the protocol.\n* Patients currently receiving experimental anti-cancer drugs (co-treatment with approved targeted therapies is permitted).\n* Patients with a history of other malignancies are eligible if they have appropriately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancers with no evidence of disease for more than 5 years.\n* Participation in another clinical trial within 30 days prior to randomization, receiving investigational drugs and any concomitant treatments containing investigational drugs.\n* Immunodeficiency, HIV infection;\n* Severe dysfunction of the heart, lungs, liver, or kidneys;\n* Uncontrolled infection or active infection;\n* Pregnant or breastfeeding women.",{"count":513,"type":21},97,[54],"The goal of this clinical trial is to learn if the intraventricular injection of Pemetrexed and Nivolumab works to treat refractory non-squamous non-small cell lung cancer with leptomeningeal metastases. The main questions to answer are:\n\n* Is the combination of Pemetrexed and Nivolumab safe to inject?\n* How effective is the combination in disease control?\n\nParticipants will：\n\n* Intrathecal injection of 30 mg pemetrexed via Ommaya reservoir, once every 4 weeks until disease progression;\n* Intrathecal injection of 40 mg nivolumab via Ommaya reservoir, once every 4 weeks until disease progression;\n* Before each intrathecal administration, a preliminary intrathecal injection of dexamethasone, 5 mg\u002F2 mL, is given.",[30],"2025-03-24",{"date":519,"type":35},"2025-03-30",{"date":521,"type":35},"2025-03-01",{"date":523,"type":21},"2027-12",{"name":525,"class":42},"Shanghai Cancer Hospital, China",{"id":527,"slug":528,"hasResults":11,"nctId":529,"briefTitle":530,"officialTitle":531,"acronym":4,"eligibilityCriteria":532,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":533,"targetDuration":4,"studyType":22,"phases":535,"briefSummary":536,"conditions":537,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":540,"lastUpdatePostDateStruct":541,"startDateStruct":543,"completionDateStruct":545,"leadSponsor":547,"locationsCount":413},"100565501","evaluating-high-dose-furmonertinib-with-bevacizumab-and-pemetrexed-for-egfrm-nsclc-with-leptomeningeal-metastasis-100565501","NCT06643000","Evaluating High-dose Furmonertinib with Bevacizumab and Pemetrexed for EGFRm NSCLC with Leptomeningeal Metastasis","A Single-center, Real-world Study Aimed At Evaluating the Efficacy and Safety of 240 Mg\u002Fd Furmonertinib Combined with Bevacizumab and Pemetrexed in the Treatment of Advanced NSCLC with EGFRm and Leptomeningeal Metastasis.","Inclusion Criteria:\n\n1. Have obtained written informed consent from the patient or his or her legal representative;\n2. The patient is ≥18 years old, male or female;\n3. Non-small cell lung cancer confirmed by histological or cytological pathology;\n4. Genetic testing confirming positive for classical or non-classical EGFR mutations;\n5. After comprehensive clinical evaluation according to the \"EANO-ESMO\" meningeal metastasis diagnostic criteria, the comprehensive clinical evaluation of patients with definite meningeal metastasis included symptom evaluation, imaging evaluation, and\u002For cerebrospinal fluid pathology evaluation;\n6. Patients with newly diagnosed leptomeningeal metastases and those with disease progression after previous antineoplastic therapy were eligible;\n7. ECOG Performance Status 0-3;\n8. Prior treatment with radiation or surgery targeting the central nervous system is permitted;\n9. Admit patients with CNS symptoms or signs, but those symptoms or signs are not life threatening;\n10. Fertile men or women with the possibility of becoming pregnant must use a highly effective method of contraception (such as oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicides) during the course of the trial and continue contraception for 12 months after the end of treatment.\n\nExclusion Criteria:\n\n* 1)Patients currently have tumors other than NSCLC; 2)Have had or have a history of other malignancies within the last 5 years, other than basal cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast that have been effectively controlled; 3)Serious digestive tract diseases that affect drug use and absorption, including but not limited to peptic ulcer, inflammatory bowel disease, etc.\n\n  4)Evidence of any severe or uncontrolled systemic disease, including uncontrolled hypertension, diabetes, and active bleeding, any that the investigator deems to be detrimental to the patient's participation in the study or to adherence to the protocol, or active infections including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV); 5)A history of interstitial lung disease, drug-induced interstitial lung disease, prior history of radiation pneumonia requiring steroid treatment, or any evidence of active interstitial lung disease; 6)The presence of significant arrhythmias (such as prolonged QT interval \\> 500ms) or heart failure (left ventricular ejection fraction \\\u003C 50%) 7)Pregnant or lactating women; 8)Patients who received a live vaccine within 4 weeks before treatment began; 9)Patients who are or have been involved in another clinical study within 4 weeks; 10)Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that, in the investigator's opinion, may increase the risks associated with participating in the study or may interfere with the interpretation of the study results; Or subjects who may not be able to complete the study or comply with the requirements of the study (for administrative or other reasons).",{"count":534,"type":21},60,[83],"The primary objective of this clinical study is to evaluate the efficacy of high-dose furmonertinib combined with bevacizumab and pemetrexed (triple therapy) in the treatment of non-small cell lung cancer (NSCLC) with leptomeningeal metastasis and epidermal growth factor receptor mutation (EGFRm) through overall survival (OS). The secondary objectives are to further assess the efficacy of the triple therapy in patients with EGFRm and leptomeningeal metastasis, including time to treatment failure (TTF), leptomeningeal objective response rate (ORR-LM), and clinical response rate.The study will also evaluate the impact of the triple therapy on quality of life using the EORTC QLQ-C30 scale and assess the safety of the therapy in EGFRm NSCLC patients with leptomeningeal metastasis, focusing primarily on adverse events and their severity (graded according to CTCAE v5.0), as well as their frequency.The exploratory objectives are to assess changes in intracranial pressure and the improvement rate of cerebrospinal fluid (CSF) before and after the triple therapy treatment. Additionally, the study will compare the genomic and epigenomic profile changes in circulating tumor DNA (ctDNA) from peripheral blood and cell-free DNA (cfDNA) from cerebrospinal fluid before and after treatment, and analyze their correlation with clinical outcomes, drug efficacy, and other clinical indicators.\n\nThe primary endpoint of this study is overall survival (OS). The secondary endpoints include time to treatment failure (TTF), leptomeningeal objective response rate (ORR-LM), clinical response rate, and quality of life assessment (EORTC QLQ-C30).The safety endpoints are adverse events and their severity (graded according to CTCAE v5.0), as well as the frequency of occurrence.\n\nA total of 60 patients are planned to be enrolled, targeting eligible advanced NSCLC patients with EGFR mutations and leptomeningeal metastasis.\n\nThe intervention consists of furmonertinib (240 mg\u002Fd, po) combined with bevacizumab (15 mg\u002Fkg, every 3 weeks, ivgtt) and pemetrexed (50 mg) intrathecal chemotherapy \u002F pemetrexed (500 mg\u002Fm²) intravenous chemotherapy, administered every 3 weeks.",[538,30,539],"Non-small Cell Lung Cancer","EGFR Gene Mutation","2025-03-03",{"date":542,"type":35},"2025-03-06",{"date":544,"type":35},"2024-12-20",{"date":546,"type":21},"2025-05-30",{"name":548,"class":149},"Henan Cancer Hospital",{"id":550,"slug":551,"hasResults":11,"nctId":552,"briefTitle":553,"officialTitle":554,"acronym":4,"eligibilityCriteria":555,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":556,"targetDuration":4,"studyType":22,"phases":557,"briefSummary":558,"conditions":559,"keywords":561,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":564,"lastUpdatePostDateStruct":565,"startDateStruct":567,"completionDateStruct":569,"leadSponsor":570,"locationsCount":43},"100459080","csf-analysis-in-egfr-mutant-non-small-cell-lung-cancer-with-leptomeningeal-disease-100459080","NCT05257967","CSF Analysis in EGFR Mutant Non-Small Cell Lung Cancer With Leptomeningeal Disease","CSF Liquid Biopsy Based Characterization of Leptomeningeal Disease in EGFR Mutant Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Subject age is greater than or equal to 18 years at the time of signature of informed consent.\n* Histologically or cytologically confirmed metastatic EGFR mutant NSCLC.\n* Leptomeningeal disease based on brain MRI or CSF cytology.\n* ECOG 0-3.\n* Life expectancy of at least 8 weeks.\n* Adequate hematologic and end organ function for testing.\n* Ability to give informed consent for the study procedures defined in this protocol.\n\nExclusion Criteria:\n\n* Inability to undergo a lumbar puncture due to thrombocytopenia, bleeding disorders, as well as inability to cooperate or consent to procedure.\n* Subjects who are otherwise felt by the treating clinician to be unfit to proceed with this protocol.\n* MRI spine demonstrating spinal leptomeningeal disease preventing a safe lumbar puncture.",{"count":20,"type":21},[83],"Leptomeningeal disease is malignant seeding of the leptomeninges and presents with a variety of symptoms frequently impacting quality of life. With improvement in treatment options, rates of leptomeningeal disease are increasing and currently found in up to 9% of EGFR mutant NSCLC.\n\nSystemic therapy may be more effective if it can target the correct molecular aberration. The molecular characterization of central nervous system disease may differ from disease outside of the central nervous system. The aim of this pilot trial is to evaluate for molecular differences between cerebral spinal fluid (CSF) and blood circulating tumor DNA (ctDNA) through the use of ddPCR and BC Cancer NGS panel molecular testing.",[111,30,560],"Non Small Cell Lung Cancer",[88,562,563],"EGFR","leptomeningeal disease","2025-02-08",{"date":566,"type":35},"2025-02-11",{"date":568,"type":35},"2022-07-18",{"date":39,"type":21},{"name":571,"class":42},"British Columbia Cancer Agency",{"id":573,"slug":574,"hasResults":11,"nctId":575,"briefTitle":576,"officialTitle":577,"acronym":4,"eligibilityCriteria":578,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":579,"targetDuration":4,"studyType":22,"phases":581,"briefSummary":582,"conditions":583,"keywords":4,"overallStatus":62,"whyStopped":4,"lastUpdateSubmitDate":584,"lastUpdatePostDateStruct":585,"startDateStruct":587,"completionDateStruct":589,"leadSponsor":591,"locationsCount":43},"100549975","phase-2-double-dose-of-third-generation-egfr-tki-plus-intrathecal-pemetrexed-versus-double-dose-of-third-generation-egfr-tki-in-patients-with-lm-progression-following-the-treatment-of-routine-dose-of-third-generation-egfr-tki-100549975","NCT06441045","Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus Double Dose of Third-generation EGFR-TKI in Patients With LM Progression Following the Treatment of Routine Dose of Third-generation EGFR-TKI","Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus Double Dose of Third-generation EGFR-TKI in NSCLC Patients With Leptomeningeal Progression Following the Treatment of Routine Dose of Third-generation EGFR-TKI: a Phase II Randomized, Multicenter Study","Inclusion Criteria:\n\n* Age 18 years at the time of signing informed consent, both sexes;\n* advanced or metastatic NSCLC, TNM stage IV according to the eighth edition of IASLC 2015;\n* with EGFR sensitive mutation (exon 19 deletion or L858R mutation), LM progression after conventional doses of three generation EGFR targeted agents (after 1 + 3,2 + 3 or direct 3-generation targeted therapy). There is no limit on the number of chemotherapy lines. The enrolled patients required brain parenchyma and extracranial lesion stable\n* ECOG PS score: 0-3\n* Normal main organ function, That is, the following criteria are met:\n\n  1. routine blood examination (no blood transfusion within 14 days, no hematopoietic stimulating factor drugs are corrected state): hemoglobin (Hb) 90g \u002F L; Absolute neutrophil count (ANC) 1.5109 \u002F L; Platelet (PLT) 100109 \u002F L; White blood cell count (WBC) 3.0109 \u002F L;\n  2. Biochemical examination: alanine transaminotransferase (ALT) and alanine transaminotransferase (AST) 2.5 upper limit of normal (ULN); Serum total bilirubin (TBIL) 1.5 ULN; Serum creatinine (Cr) of 1.5 ULN or creatinine clearance of 50 ml\u002Fmin; If any liver metastasis, Then, the total bilirubin 3 ULN, ALT and AST 5 ULN; C) Coagulation function: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time 12 (PT) 1.5 ULN;\n\n  d) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) 50%;\n* If previously treated with chemotherapy, A washout period of at least 21 days between the last chemotherapy dose and enrollment (if the patient does not receive radiotherapy) is required; Patients who treated brain parenchymal metastases with local radiotherapy or surgery before enrollment, Must be completed and fully recovered from the acute toxicity of radiotherapy \u002F surgery. A minimum 14-day washout period is required between the end of radiotherapy and enrollment. A minimum 30-day washout period is required between the end of surgery and enrollment.\n* Expected survival of not less than 3 months\n* patients can swallow oral medication (if not oral, can be ground by gastric tube)\n* Women of childbearing age must have negative pregnancy test (serum or urine) within 14 days before observation period and 3 months after the last administration; for men, they should undergo surgical sterilization or agree to use appropriate contraception during the observation period and 3 months after the last administration of study drug\n* patients voluntarily participate and sign an informed consent (or legal agent), expected to have good compliance and able to cooperate with the study according to the protocol requirements.\n\nExclusion Criteria:\n\n* Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the study program;\n* Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS)\n* patient with active bacterial infection, fungal infection (intravenous antibiotics required at initiation of study treatment);\n* past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid therapy, Or any signs of clinically active interstitial lung disease;\n* arterial \u002F venous thrombosis events within 6 months prior to enrollment, Such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;\n* congestive heart failure (NYHA grade\\> 2); unstable angina pectoris; a myocardial infarction within 3 months prior to signing an ICF; any 12 supraventricular or ventricular arrhythmia requiring treatment or intervention; Mean QTcF\\> 470ms from 3 ECG recordings\n* other systemic malignancies in the last 5 years, (Except for cured skin basal cell carcinoma and cervical situ carcinoma and ovarian carcinoma);\n* Use drugs or supplements known to be the main cause of CYP3A4.\n* Persons known to be allergic to any test drug or its excipients;\n* pregnant, lactating, reproductive patients unwilling to use effective contraception; ●a clear prior history of neurological or psychiatric disorders, including epilepsy and dementia;\n* other conditions considered inappropriate by the investigator.",{"count":580,"type":21},112,[54],"We aim to compare the efficacy and safety of double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus double Dose of Third-generation EGFR-TKI in patients with leptomeningeal progression following the treatment of routine dose of EGFR-TKI,",[30],"2024-06-03",{"date":586,"type":35},"2024-06-04",{"date":588,"type":21},"2024-10-01",{"date":590,"type":21},"2028-10-01",{"name":592,"class":149},"Fujian Cancer Hospital",{"id":594,"slug":595,"hasResults":11,"nctId":596,"briefTitle":597,"officialTitle":597,"acronym":598,"eligibilityCriteria":599,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":600,"targetDuration":4,"studyType":401,"phases":4,"briefSummary":602,"conditions":603,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":606,"lastUpdatePostDateStruct":607,"startDateStruct":609,"completionDateStruct":611,"leadSponsor":613,"locationsCount":615},"100548185","standardized-clinical-assessment-of-patients-with-leptomeningeal-metastasis-100548185","NCT06417710","Standardized Clinical Assessment of Patients With Leptomeningeal Metastasis","NANO-LM","Inclusion Criteria:\n\n* Adult patients (18 years or more), female or male\n* Histologically confirmed diagnosis of extra-CNS primary solid cancer\n* Diagnosis of leptomeningeal metastases confirmed or probable per EANO ESMO criteria\n* Performance status compatible with enrolment into clinical trials\n* Ability to consent\n* Signed informed consent form from patient\n* Participation in a parallel clinical trial is allowed in this non-interventional study\n\nExclusion Criteria:\n\n* Inability to give informed consent\n* Inability to adhere to recommended follow-up according to the treating physician\n\nVulnerable participants will not be included.",{"count":601,"type":21},200,"The goal of this project is to develop and validate a reproducible scorecard for the neurological assessment of patients with leptomeningeal metastases that can be used in clinical trials including such patients, as well as in clinical practice.",[30,265,604,605],"Leptomeningeal Neoplasms","Leptomeningeal Cancer","2024-05-12",{"date":608,"type":35},"2024-05-16",{"date":610,"type":35},"2022-01-30",{"date":612,"type":21},"2026-12",{"name":614,"class":42},"University of Zurich",3,{"id":617,"slug":618,"hasResults":11,"nctId":619,"briefTitle":620,"officialTitle":621,"acronym":4,"eligibilityCriteria":622,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":623,"targetDuration":4,"studyType":401,"phases":4,"briefSummary":625,"conditions":626,"keywords":628,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":630,"lastUpdatePostDateStruct":631,"startDateStruct":633,"completionDateStruct":635,"leadSponsor":637,"locationsCount":43},"100546820","efficacy-and-safety-of-intraventricule-pemetrexed-disodium-administered-via-ommaya-reservoir-100546820","NCT06399926","Efficacy and Safety of Intraventricule Pemetrexed Disodium Administered Via Ommaya Reservoir","A Open-label, Random, Multi-central Prospective Cohort of Observation Study on the Efficacy and Safety of Intraventricule Pemetrexed Disodium Via Ommaya Reservoir","Inclusion Criteria:\n\n1. confirmed pathologic diagnosis (histologic type of non-squamous non-small cell lung cancer in the primary lesion or metastatic lesion) with definitely genetic testing results (EGFR\u002FALK\u002FROS1);\n2. In accordance with the CSCO Guidelines for the Diagnosis and Management of Central Nervous System Tumors, and the EANO-ESMO diagnostic criteria: a diagnosis of type I meningeal metastatic carcinoma is made when cerebrospinal fluid cytology testing reveals anisocytosis (3 consecutive tests are required if the cerebrospinal fluid cytology testing is initially negative for the patient) (one study showed that the specificity of anisocytosis in diagnosing meningeal metastases in patients with solid tumors was 100%) or meningeal lesions Biopsy confirms the diagnosis. (Type IIA-C meningeal metastases: negative or atypical cerebrospinal fluid cytology, MRI showing linear or\u002Fand nodular meningeal enhancement\\^ with typical clinical symptoms\\*).\n\n   * MRI: at least 1.5T; demonstrates sulcal, smear, or linear ventricular enhancement, cranial nerve root enhancement or nodular meningeal enhancement, or cauda equina spinal enhancement; control enhancement T1-weighted sequences and Flair sequences; nodularity is defined as foci of ≥ 5x10mm enhancement; sequences of choice: cranial planar enhancement + T2Flair (enhancement) or and total spinal planar enhancement (when suspicion of spinal involvement); 3D T1 enhancement (involved cranial nerves - optional); cerebrospinal fluid flow imaging (functional or anatomic).\n\n     * Typical clinical manifestations: headache, nausea, vomiting; epilepsy; mental changes, gait difficulties; cranial nerve damage (diplopia, visual abnormalities, hearing abnormalities, facial nerve palsy, difficulty chewing, difficulty swallowing, choking, etc.); neurogenic signs (cauda equina symptoms, mainly perineal numbness, tingling, defecation and urination disturbances, weakness or incomplete paralysis of both lower limbs); sensorimotor defects of the limbs; cervical back Radicular pain; be careful to differentiate from signs and symptoms of brain parenchymal metastases, extracranial disease, treatment-related adverse effects, and non-tumor comorbidities.\n\n       3\\. Based on the guideline-driven first-line choice of TKI agents for gene-positive patients, enrolment would therefore require: failure of at least three generations of EGFR-TKIs for patients with EGFR mutations; failure of at least second-generation ALK inhibitors for ALK mutations; and failure of at least one ROS1 inhibitor for ROS1 mutations.\n\n       4\\. No contraindication to Ommaya capsule implantation. 5. Female subjects who are capable of becoming pregnant must agree to use reliable contraception throughout the trial; male subjects whose female partner is capable of becoming pregnant must agree to use reliable contraception throughout the trial.\n\n       6\\. patients must sign an informed consent form and must be willing and able to comply with visits, treatment regimens, laboratory tests and other requirements as specified in the study protocol\n\nExclusion Criteria:\n\n1. HBsAg-positive patients may be enrolled, but patients with higher than normal viral copy number or HBcAb-positive patients should receive effective anti-HBV treatment until 6 months after the end of the trial. HCV RNA carriers may be enrolled, but need to receive effective anti-HCV treatment throughout the trial, and continue to receive effective anti-HCV treatment until 6 months after the end of the trial.\n2. human immunodeficiency virus (HIV) infection.\n3. significant extracranial lesion progression or extensive extracranial lesions causing severe symptoms that cannot be effectively treated.\n4. patients with extreme emaciation or cachexia.\n5. Extensive parenchymal brain lesions with severe symptoms that cannot be effectively treated.\n6. patients with other malignant tumors that are currently undergoing treatment.\n7. have received or will receive a live vaccine within 30 days prior to signing the informed consent form.\n8. other conditions that, in the judgment of the investigator, may affect subject safety or trial compliance, including symptomatic heart failure, unstable angina, myocardial infarction, active infections (including tuberculosis infections) requiring systemic therapy; or severe organ dysfunction, with creatinine clearance \\\u003C45 ml\u002Fmin calculated from glomerular filtration rate by the Cockcroft-Gault formula or by the Tc99m-DPTA serum clearance method; an absolute neutrophil count \\\u003C0.5 x 109\u002FL; a platelet count \\\u003C25 x 109\u002FL, or in patients with severe active visceral bleeding; or severe Abnormal liver function (bilirubin greater than 3.0 times upper limit of normal; AST and ALT greater than 5.0 times upper limit of normal).\n9. patients with known hypersensitivity to pemetrexed with a history of serious adverse reactions, and patients with potentially life-threatening conditions for reuse.\n10. pregnant or lactating women.",{"count":624,"type":21},64,"This is a open-label, multi-center prospective observation study for the efficacy and safety of intraventricle pemetrexed disodium via ommaya reservoir in the treatment of leptomeningeal metastasis with lung cancer who have failed at least one targeted therapy. In detail: At least the treatment failure was after third-generation EGFR-TKIs in EGFR-mutated lung cancer; or at least the treatment failure was after second-generation ALK-TKIs in ALK-mutated lung cancer; or at least the treatment failure was after one-line of targeted-TKIs in ROS1-mutated non-squamous non-small lung cancer.",[30,627],"Lung Cancer",[30,629,217],"Ommaya reservoir","2024-05-03",{"date":632,"type":35},"2024-05-06",{"date":634,"type":35},"2023-10-30",{"date":636,"type":21},"2027-06-30",{"name":638,"class":42},"Xiangya Hospital of Central South University"]