[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"leptomeningeal-metastases\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:leptomeningeal-metastases":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,7,0,[8,39,66,96,122,147,178],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":28,"lastUpdatePostDateStruct":29,"startDateStruct":32,"completionDateStruct":34,"leadSponsor":36,"locationsCount":4},"100644687","phase-1-phase-1-study-of-wbrt-or-pcsi-with-reyobiq-for-leptomeningeal-metastases-100644687",false,"NCT07674693","Phase 1 Study of WBRT or PCSI With REYOBIQ for Leptomeningeal Metastases","A Phase 1 Study to Determine the Safety and Tolerability of Whole Brain Radiotherapy (WBRT) or Proton Craniospinal Irradiation (PCSI) With Multiple Doses of Rhenium-186 NanoLiposome (186RNL, REYOBIQ) Administered Via Intraventricular Catheter for Leptomeningeal Metastases","Inclusion Criteria:\n\n* At least 18 years of age at screening\n* Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB\n* Proven and documented LM evidenced by positive CSF cytology or CSF circulating tumor cells, from any primary solid tumor\n* Patients may have received prior chemotherapy regimens and prior radiation (there is no limit)\n* Karnofsky performance status of 60 to 100\n* Acceptable liver function:\n\n  * Bilirubin ≤ 1.5 times upper limit of normal\n  * AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal for subjects with normal liver\n  * AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects with liver metastasis\n* Subjects with a creatinine clearance greater than or equal to 60 mL\u002Fmin (using the Cockcroft-Gault Equation) for males and females.\n* Acceptable hematologic status (without hematologic support):\n\n  * ANC ≥ 1000 cells μL\n  * Platelet count ≥ 75,000\u002FμL\n  * Hemoglobin ≥ 9.0 g\u002FdL\n  * PT\u002FINR and PTT ≤1.5 x ULN, unless treated with anticoagulants\n* 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.\n\nExclusion Criteria:\n\n* The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v6.0) Grade ≤ 1 from AEs due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study. Prior AEs due to alopecia, anemia, and lymphopenia are not required to be recovered to Grade ≤ 1 prior to 186RNL treatment, assuming other inclusion criteria are satisfied.\n* Ventriculo-peritoneal or ventriculo-atrial shunts or contraindications to placement of Ommaya reservoir.\n* Females of childbearing potential who are pregnant, breast feeding, or may possibly be pregnant without a negative serum pregnancy test (see inclusion criteria).\n* Serious intercurrent illness, clinically significant cardiac arrhythmias, uncontrolled systemic infection, symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug, myocardial infarction, stroke, transient ischemic attack within 6 months, seizure disorder with any seizure occurring within 14 days prior to consenting or encephalopathy.\n* Active severe non hematologic organ dysfunction such as renal, cardiac, hepatic, pulmonary, or gastrointestinal grade 3 or above.\n* Toxicity from prior treatments (grade 3 or above) that have not subsided to grade 1.\n* Patients with prior CNS directed EBRT.\n* Cytotoxic systemic therapy is excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment. Small-molecule kinase inhibitors, targeted therapies, immunotherapy, and hormonal therapy can be given up to the day of treatment per investigator discretion.\n* Projected survival of less than 60 days.","ALL","18 Years",{"count":19,"type":20},29,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","This Phase 1 study is designed to assess the safety, tolerability, and schedule feasibility of administering Rhenium-186 NanoLiposome (REYOBIQ) at different dosing intervals following whole brain radiotherapy (WBRT) or proton craniospinal irradiation (PCSI).",[26],"Leptomeningeal Metastases","NOT_YET_RECRUITING","2026-06-23",{"date":30,"type":31},"2026-06-29","ACTUAL",{"date":33,"type":20},"2026-07",{"date":35,"type":20},"2031-07",{"name":37,"class":38},"NYU Langone Health","OTHER",{"id":40,"slug":41,"hasResults":11,"nctId":42,"briefTitle":43,"officialTitle":44,"acronym":4,"eligibilityCriteria":45,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":46,"targetDuration":4,"studyType":21,"phases":48,"briefSummary":49,"conditions":50,"keywords":51,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":57,"lastUpdatePostDateStruct":58,"startDateStruct":60,"completionDateStruct":62,"leadSponsor":64,"locationsCount":5},"100453459","phase-1-a-study-of-deferoxamine-dfo-in-people-with-leptomeningeal-metastasis-100453459","NCT05184816","A Study of Deferoxamine (DFO) in People With Leptomeningeal Metastasis","A Phase 1a\u002F1b Trial of Intrathecal Deferoxamine for Leptomeningeal Metastases","Inclusion Criteria:\n\n* Age ≥ 18 years on the day of consenting to study\n* ECOG performance status ≤ 2 or KPS ≥ 60.\n* Life expectancy ≥ 8 weeks in the opinion of the Investigator\n* LM from any solid tumor malignancy (1a and 1b), that is either:\n\n  * Newly diagnosed: As evidenced by positive CSF cytology, CTC count \\>3.0\u002F3.0 mL, or unequivocal radiographic evidence of LM on contrast-enhanced MRI, OR\n  * Recurrent: As evidenced by unequivocal radiographic progression on contrast-enhanced MRI, the development of newly or recurrently positive CSF cytology, or a clinically-relevant rise in CSF CTCs at the discretion of the treating Investigator. There are no restrictions on the number of recurrences.\n\nOR\n\n* Persistent: As evidenced by any detectable disease (abnormal leptomeningeal enhancement on contrast-enhanced MRI; positive, suspicious, or atypical cytology; positive CSF CTCs; extrinsic cells on CSF cell count differential; or clinical symptoms attributed to LM) after receiving LM-directed radiation or systemic therapy. This includes patients with stable or partially responding LM who, in the opinion of the investigator, would benefit from additional LM-directed therapy.\n\n  * Confirmation of solid tumor malignancy (phase 1a and 1b) may be made by histopathologic criteria of any primary or metastatic site. For patients that have not previously undergone internal pathology review at MSKCC, a pathology report confirming the primary malignancy is sufficient.\n  * Patients can have concomitant parenchymal brain metastases at study entry as long as they do not require active treatment or have been previously treated.\n  * Patients with seizure disorders, stable on appropriate antiepileptic therapies, are eligible for this trial.\n  * Patients must have normal CSF flow dynamics at the clinical judgment of the treating investigator, with no obstructive hydrocephalus or ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt.\n  * Patients with isolated intracranial LM progression and stable extracranial disease may enroll on trial. If this population is receiving systemic treatment that is controlling their extracranial disease, they may remain on this regimen during study enrollment provided their LM progression occurred on this regimen.\n  * For patients with both intracranial and extracranial disease progression at the time of study screening, necessitating change to their systemic tumor-directed therapy:\n* If the new systemic treatment of choice has known CNS activity at the discretion of the Principal Investigator, then they should be monitored on this new regimen for 21 days with confirmation of persistent LM (by neuraxial imaging and CSF reassessment) before enrolling on study.\n* If the new systemic treatment of choice has no known CNS activity at the discretion of the Principal Investigator, then they may start IT-DFO concurrently with the new systemic treatment.\n* Examples of systemic CNS-active treatments include but are not limited to: bevacizumab, temozolomide, carmustine, lomustine, etoposide, carboplatin, cisplatin, pemetrexed, doxorubicin, high-dose erlotinib, osimertinib, lorlatinib, lapatinib, tucatinib, capecitabine, dabrafenib, trametinib, vemurafenib, cobimetinib, ipilimumab, nivolumab, pembrolizumab, atezolizumab\n\n  * Patients must have a functioning Ommaya reservoir prior to the first IT-DFO administration or be an appropriate surgical candidate for Ommaya reservoir placement and agree to Ommaya reservoir placement as standard of care prior to the first IT-DFO administration.\n  * Patients that have screening laboratory values out of range, but not clinically significant, may be considered eligible on a case by case basis deemed by the clinical investigator. Adequate bone marrow and organ function is demonstrated by:\n* White blood cell (WBC) count ≥ 2.5 K\u002FmcL or if this value is less, an exemption has been granted by the treating physician or primary investigator.\n* Absolute neutrophil count (ANC) ≥ 1.0 K\u002FmcL\n* Platelet count ≥ 50 K\u002FmcL at least 7 days from last platelet transfusion, or if this value is less, an exemption has been granted by the treating physician or primary investigator.\n* Hemoglobin (Hgb) ≥ 8 g\u002FdL, or if this value is less, an exemption has been granted by the treating physician or primary investigator.\n* Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or if this value is more, an exemption has been granted by the treating physician or primary investigator.\n* Serum bilirubin ≤ 1.5 times the ULN; or total bilirubin ≤ 3 times the ULN with direct bilirubin within the normal range in patients with well documented Gilbert Disease or if this value is more, an exemption has been granted by the treating physician or primary investigator.\n* Serum alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) ≤ 3 times the ULN, unless known hepatic disease wherein may be ≤ 5 times the ULN is acceptable. If this value is more, an exemption must be granted by the treating physician or primary investigator.\n\n  * Women of child-bearing potential and sexually active males must commit to the use of effective contraception while on study.\n\nExclusion Criteria:\n\n* Any CNS-directed irradiation within 7 days of first dose of IT-DFO.\n* Patients receiving other therapy (either intrathecal or systemic) designed to treat their LM, with ongoing acceptable control of their LM.\n* Any contraindication to gadolinium-enhanced MRI\n* Use of any systemic iron chelators within 4 weeks of first dose\n* Use of ascorbic acid or prochlorperazine within 2 weeks of first dose\n* Patients are not allowed to receive whole-brain radiation therapy or craniospinal radiation therapy during study enrollment.\n* Patients must not have any physical and\u002For psychiatric illness that would interfere with their compliance and ability to tolerate treatment as per the protocol.\n* Women may not be pregnant or breastfeeding\n* Known hypersensitivity orSpecial Characters",{"count":47,"type":20},35,[23],"The researchers are doing this study to find out whether deferoxamine (DFO) given intrathecally (directly into the CSF) is a safe treatment for people with leptomeningeal metastasis from solid tumor cancer. The researchers will test different doses of DFO to find the highest dose that causes few or mild side effects. When the dose is found, they will test it in future participants to see whether DFO is a safe and effective treatment for people with leptomeningeal metastasis from solid tumor malignancies. They are also doing this study to see how the body absorbs, distributes, gets rid of, and responds to DFO.",[26],[52,53,54,55],"Deferoxamine (DFO)","21-378","recurrent","persistent","RECRUITING","2026-03-25",{"date":59,"type":31},"2026-03-27",{"date":61,"type":31},"2021-12-22",{"date":63,"type":20},"2026-12",{"name":65,"class":38},"Memorial Sloan Kettering Cancer Center",{"id":67,"slug":68,"hasResults":11,"nctId":69,"briefTitle":70,"officialTitle":71,"acronym":4,"eligibilityCriteria":72,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":73,"enrollmentInfo":74,"targetDuration":4,"studyType":21,"phases":76,"briefSummary":78,"conditions":79,"keywords":80,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":86,"lastUpdatePostDateStruct":87,"startDateStruct":89,"completionDateStruct":91,"leadSponsor":93,"locationsCount":95},"100551592","phase-1-sacituzumab-govitecan-and-intrathecal-chemotherapy-for-treating-leptomeningeal-metastases-from-her2-negative-breast-cancer-100551592","NCT06462092","Sacituzumab Govitecan and Intrathecal Chemotherapy for Treating Leptomeningeal Metastases From Her2-negative Breast Cancer","A Phase I\u002FII Clinical Study of Sacituzumab Govitecan Combined With Intrathecal Chemotherapy for the Treatment of Leptomeningeal Metastases From Her2-negative Breast Cancer","Inclusion Criteria:\n\n1. A clear histopathologic diagnosis of breast cancer with HER2-negative subtype (including IHC 0, IHC 1+ or IHC 2+ and ISH negative);\n2. Cerebrospinal fluid cytology confirms the presence of leptomeningeal metastases; or imaging findings combined with clinical symptoms and signs are consistent with the diagnosis of leptomeningeal metastases;\n3. Age ≥ 18 years old.\n\nExclusion Criteria:\n\n1. Inadequate organ function: 1) Blood tests: ANC ≤ 1.5 x 10\\^9\u002FL, PLT ≤ 90 x 10\\^9\u002FL, Hb ≤ 90 g\u002FL; 2) Blood biochemistry tests: TBIL ≥ 1.5 times the upper limit of normal; 3) ALT and AST ≥ 2.5 times the upper limit of normal;\n2. Presence of serious and\u002For uncontrolled comorbidities that may affect participation: 1) Allergy to study drugs or adjuvant materials; 2) History of immunodeficiency (e.g., HIV-positive or other acquired or congenital immunodeficiency disease); 3) Severe concomitant diseases;\n3. Pregnant and breastfeeding female patients; women of childbearing age who are unwilling or unable to use effective contraception;\n4. Any other condition that, in the opinion of the investigator, makes the patient ineligible for participation in the study.","75 Years",{"count":75,"type":20},34,[23,77],"PHASE2","Leptomeningeal metastases (LM) is a lethal complication of malignant tumors, characterized by tumor cell invasion and proliferation within the subarachnoid space. LM from HER2-negative breast cancer remains challenging to treat, with a median overall survival of only 3-6 months despite aggressive therapy. This open-label, uncontrolled Phase I\u002FII clinical study aims to evaluate the safety, feasibility, and potential efficacy of Sacituzumab Govitecan in combination with intrathecal pemetrexed chemotherapy for LM from HER2-negative breast cancer, with the objective of identifying a more effective treatment strategy.",[26],[81,82,26,83,84,85],"Breast cancer","Her2- (Human Epidermal Growth Factor Receptor 2 Negative)","Sacituzumab Govitecan","Pemetrexed","Intrathecal chemotherapy","2025-09-24",{"date":88,"type":31},"2025-09-29",{"date":90,"type":20},"2026-01-01",{"date":92,"type":20},"2027-06-15",{"name":94,"class":38},"Guangzhou Medical University",1,{"id":97,"slug":98,"hasResults":11,"nctId":99,"briefTitle":100,"officialTitle":101,"acronym":102,"eligibilityCriteria":103,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":104,"targetDuration":4,"studyType":21,"phases":106,"briefSummary":107,"conditions":108,"keywords":4,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":112,"lastUpdatePostDateStruct":113,"startDateStruct":115,"completionDateStruct":117,"leadSponsor":119,"locationsCount":4},"100590744","phase-2-high-dose-firmonertinib-combined-with-bevacizumab-and-intrathecal-pemetrexed-in-the-treatment-of-egfr-mutated-non-small-cell-lung-cancer-with-leptomeningeal-metastasis-100590744","NCT06971406","High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis","A Multicenter, Prospective Phase II Clinical Study of High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis","FLAME-1","Inclusion Criteria:\n\n1. Have obtained written informed consent from the patient or his or her legal representative.\n2. Age ≥18 years, male or female.\n3. Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC).\n4. EGFR mutations confirmed by genetic testing (EGFR Ex19del\u002FL858R\u002FEx20ins\u002FPACC\u002FL861Q).\n5. Leptomeningeal metastasis diagnosed by comprehensive clinical assessment according to \"EANO-ESMO\" diagnostic criteria, including symptom evaluation, imaging assessment, and\u002For cerebrospinal fluid (CSF) cytopathological evaluation.\n6. Both treatment-naïve leptomeningeal metastasis patients and those who progressed after standard antitumor therapies in clinical practice are eligible. ≤3 prior lines of therapy allowed (patients with \\>3 prior lines may enroll in the real-world study cohort).\n7. ECOG PS 0-2 (patients with ECOG PS \\>2 may enroll in the real-world study cohort).\n8. Prior radiotherapy or surgical treatment targeting the central nervous system (CNS) is permitted.\n9. Patients with CNS symptoms\u002Fsigns are allowed if these manifestations are not life-threatening.\n10. Patients previously treated with standard-dose third-generation EGFR TKIs, pemetrexed intravenous infusion, or bevacizumab are permitted.\n11. Adequate organ function:\n\n    Absolute neutrophil count (ANC) ≥1.5×10\\^9\u002FL, platelets ≥75×10\\^9\u002FL, hemoglobin ≥80g\u002FL Total bilirubin ≤1.5×ULN, AST\u002FALT ≤2.5×ULN (≤3×ULN for bilirubin and ≤5×ULN for AST\u002FALT in cases with liver metastasis) Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL\u002Fmin (calculated by Cockcroft-Gault formula).\n12. Sexually active males or females of childbearing potential must use highly effective contraception (e.g., oral contraceptives, IUD, abstinence, or barrier methods with spermicide) during the trial and for 12 months after treatment completion.\n\nExclusion Criteria:\n\n1. Diagnosis of other malignancies within the past 5 years or history of other malignancies (except adequately controlled basal cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast).\n2. Severe gastrointestinal disorders affecting drug administration or absorption, including but not limited to peptic ulcer disease, inflammatory bowel disease, etc.\n3. Known or suspected hypersensitivity to the investigational drugs (Firmonertinib, Bevacizumab, Pemetrexed) or any of their excipients.\n4. Prior treatment with high-dose third-generation EGFR TKI or intrathecal chemotherapy with Pemetrexed.\n5. Evidence of any severe or uncontrolled systemic diseases, including uncontrolled hypertension, diabetes, active bleeding, or active infections (e.g., hepatitis B\u002FC, HIV), which in the investigator's judgment may jeopardize patient participation or protocol compliance.\n6. History of steroid-requiring radiation pneumonitis or any evidence of active interstitial lung disease.\n7. Clinically significant cardiac arrhythmias (e.g., QTc interval \\>500 ms) or heart failure (left ventricular ejection fraction \\\u003C50%).\n8. Pregnant or lactating women.\n9. Patients currently participating in or having received investigational drug therapy within 2 weeks prior to enrollment.\n10. Other severe acute\u002Fchronic medical or psychiatric conditions or laboratory abnormalities that, in the investigator's opinion, may increase study-related risks, interfere with result interpretation, or compromise the patient's ability to complete the study or adhere to protocol requirements.",{"count":105,"type":20},100,[77],"Primary Objective:\n\nTo evaluate the efficacy of high-dose firmonertinib combined with bevacizumab and intrathecal pemetrexed in EGFR Ex19del\u002FL858R-mutated non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM), as measured by Overall Survival (OS).\n\nSecondary Objectives:\n\n1. To assess the efficacy of this regimen in EGFR Ex20ins\u002FPACC\u002FL861Q-mutated NSCLC with LM.\n2. To further evaluate therapeutic outcomes across cohorts, including:\n\n   * Time to Treatment Failure (TTF)\n   * Leptomeningeal Objective Response Rate (ORR-LM)\n   * Clinical Response Rate\n3. To analyze the impact of this regimen on \\*quality of life\\* using standardized metrics:\n\n   * EORTC QLQ-C30\n   * EORTC QLQ-LC13\n4. To assess safety profiles across cohorts, focusing on:\n\n   * Incidence and severity of adverse events (AEs) graded per \\*CTCAE v5.0\\*\n   * Frequency of treatment-related toxicities\n\nExploratory Objectives:\n\nTo investigate correlations between dynamic changes in:\n\n* Plasma-derived circulating tumor DNA (ctDNA)\n* Cerebrospinal fluid-derived cell-free DNA (cfDNA) and clinical outcomes through comparative analysis of genomic profiling and epigenetic signatures before and after treatment.",[109,110,26,111],"Non Small Cell Lung Cancer","EGFR Mutation","Targeted Therapy","2025-05-06",{"date":114,"type":31},"2025-05-14",{"date":116,"type":20},"2025-05-15",{"date":118,"type":20},"2027-06-01",{"name":120,"class":121},"Qiming Wang","OTHER_GOV",{"id":123,"slug":124,"hasResults":11,"nctId":125,"briefTitle":126,"officialTitle":127,"acronym":4,"eligibilityCriteria":128,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":73,"enrollmentInfo":129,"targetDuration":4,"studyType":21,"phases":131,"briefSummary":132,"conditions":133,"keywords":134,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":138,"lastUpdatePostDateStruct":139,"startDateStruct":141,"completionDateStruct":143,"leadSponsor":145,"locationsCount":95},"100582277","phase-2-cerebrospinal-fluid-cytology-guided-intrathecal-chemo-holiday-therapy-for-egfr-positive-nsclc-leptomeningeal-metastases-100582277","NCT06861218","Cerebrospinal Fluid Cytology-guided Intrathecal Chemo-holiday Therapy for EGFR-positive NSCLC Leptomeningeal Metastases","Cerebrospinal Fluid Cytology-guided Intrathecal Chemo-holiday Therapy for EGFR-positive NSCLC Meningeal Metastases: a One-arm, Phase II Clinical Study","Inclusion Criteria:\n\n1. Male or female aged between 18 and 75 years.\n2. Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations.\n3. Cytologically confirmed diagnosis of leptomeningeal metastasis.\n4. Normal organ function.\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":130,"type":20},42,[77],"With the rapid development of targeted drugs, the treatment of patients with leptomeningeal metastasis has become a very difficult problem in clinical work. High-dose targeted drugs and intrathecal chemotherapy are important treatment methods for meningeal metastasis. However, it is vital to note that safety is also of concern in previous studies of intrathecal chemotherapy. In this study, we aim to evaluate the safety and effectiveness of patient using chemo-holiday therapy based on the cerebrospinal fluid cytology, combined with double-dose EGFR-targeted drug in patients with leptomeningeal metastases from EGFR-positive NSCLC.",[26],[26,135,84,136,137],"EGFR","intrathecal injection","vometinib","2025-03-05",{"date":140,"type":31},"2025-03-06",{"date":142,"type":20},"2025-04",{"date":144,"type":20},"2028-12",{"name":146,"class":38},"Zhejiang Cancer Hospital",{"id":148,"slug":149,"hasResults":11,"nctId":150,"briefTitle":151,"officialTitle":152,"acronym":4,"eligibilityCriteria":153,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":73,"enrollmentInfo":154,"targetDuration":4,"studyType":21,"phases":156,"briefSummary":158,"conditions":159,"keywords":164,"overallStatus":27,"whyStopped":4,"lastUpdateSubmitDate":169,"lastUpdatePostDateStruct":170,"startDateStruct":172,"completionDateStruct":174,"leadSponsor":176,"locationsCount":4},"100575000","ivonescimab-combined-with-chemotherapy-for-the-treatment-of-leptomeningeal-metastases-failed-to-egfr-tkis-100575000","NCT06766591","Ivonescimab Combined With Chemotherapy for the Treatment of Leptomeningeal Metastases Failed to EGFR-TKIs","Ivonescimab Combined With Chemotherapy for EGFR Mutant NSCLC With Leptomeningeal Metastasis After EGFR TKIs Resistance: A Multicenter Observational Study.","Inclusion Criteria:\n\n* Age range: 18-75y\n* EGFR mutation NSCLC\n* LM was diagnosed through head enhanced MRI or (and) CSF cytology\n* EGFR activation mutations were positive\n* Patients who have failed to first or second-generation EGFR-TKI treatment，without T790M mutation; or failed to third-generation EGFR-TKI treatment\n* Hematological, coagulation, renal and liver function is sufficient\n* Women of childbearing age must undergo a pregnancy test and the result must be negative\n\nExclusion Criteria:\n\n* Patients with squamous cell carcinoma, large cell carcinoma, mixed cell lung cancer\n* The patient has other driver genes that can be treated with targeted drugs\n* Subjects who have previously received immunotherapy with a discontinuation time of less than 3 months\n* Received EGFR-TKI treatment within one week prior to the first administration\n* Received non-specific immunomodulatory therapy\n* Clinical manifestations of neurological failure\n* Non malignant neurological disorders\n* Radiotherapy for the chest and whole brain should be completed within 4 weeks before enrollment\n* Tumor surrounded important blood vessels or had obvious necrosis or cavities\n* Tumor has invaded important surrounding organs and blood vessels\n* History of severe bleeding tendency or coagulation dysfunction\n* The risk of developing esophagotracheal fistula or esophageal pleural fistula",{"count":155,"type":20},36,[157],"NA","Research objective Main purpose Exploring the real-world effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis after EGFR-TKIs resistance. Outcome measure: Real world intracranial disease-free survival time (iPFS).\n\nSecondary purpose Federation patterns: describing different treatment modes in the real world; Outcome measures: Combination chemotherapy regimen and duration of chemotherapy.\n\nEfficacy: Further explore the effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis failed with EGFR-TKI treatment; Outcome measures: Objective response rate (LM-ORR), duration of intracranial response (iDoR), overall progression free survival (PFS), overall survival (OS), improvement in neurological function, CSF response rate based on CSF cytology.\n\nSafety: Explore the safety of Ivonescimab combined with chemotherapy for NSCLC patients with leptomeningeal metastases who have failed EGFR-TKI treatment; Outcome measures: incidence of adverse events (TEAEs), laboratory test outliers, and serious adverse events (SAEs).\n\nResearch endpoint Primary endpoint\n\n* iPFS (intracranial progression free survival). Secondary endpoint\n* Efficacy: leptomeningeal ORR (LM-ORR), intracranial duration of response (iDoR), overall progression free survival (PFS), overall survival (OS), improvement in neurological function, and CSF response rate based on CSF cytology;\n* Safety: Determine the incidence and severity of adverse events (AE) and serious adverse events (SAE) according to NCI-CTCAE5.0 standards; Changes in vital signs, laboratory abnormalities, and quality of life scores.\n\nExploratory endpoint: efficacy related biomarkers",[160,161,26,162,163],"NSCLC","Chemotherapy","EGFR-TKI","AK112",[165,160,166,162,167,168],"Ivonescimab","leptomeningeal metastases","VEGF","PD-1\u002FVEGF bispecific antibody","2025-01-05",{"date":171,"type":31},"2025-01-09",{"date":173,"type":20},"2025-01-01",{"date":175,"type":20},"2025-10-31",{"name":177,"class":38},"Jiangsu Province Nanjing Brain Hospital",{"id":179,"slug":180,"hasResults":11,"nctId":181,"briefTitle":182,"officialTitle":182,"acronym":183,"eligibilityCriteria":184,"healthyVolunteers":11,"sex":16,"minAge":185,"maxAge":73,"enrollmentInfo":186,"targetDuration":4,"studyType":21,"phases":188,"briefSummary":189,"conditions":190,"keywords":4,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":195,"lastUpdatePostDateStruct":196,"startDateStruct":198,"completionDateStruct":200,"leadSponsor":202,"locationsCount":95},"100572099","phase-2-evaluation-of-the-efficacy-and-safety-of-furmonertinib-combined-with-bevacizumab-as-first-line-treatment-for-egfr-positive-non-small-cell-lung-cancer-with-brain-metastases-a-single-arm-open-label-prospective-phase-ii-clinical-study-100572099","NCT06728865","Evaluation of the Efficacy and Safety of Furmonertinib Combined with Bevacizumab As First-Line Treatment for EGFR-Positive Non-Small Cell Lung Cancer with Brain Metastases: a Single-Arm, Open-Label, Prospective Phase II Clinical Study","Better Brain","Inclusion Criteria:\n\n1. Aged 18-75 years. ECOG performance status (PS) score of 0-2. Expected survival time of ≥3 months.\n2. Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC).\n3. Baseline evaluation confirming the presence of EGFR-sensitizing mutations (19del\u002FL858R) via first- or second-generation sequencing. Test samples can include archived tumor tissue or fresh tumor tissue collected during screening. If unavailable, pleural effusion, cerebrospinal fluid, or blood samples may be used for testing.\n4. Asymptomatic brain metastases or those with controlled intracranial hypertension symptoms following dehydration treatment. Continued medication to maintain stable symptoms at enrollment or during the study is allowed.\n5. For patients with parenchymal or leptomeningeal brain metastases, MRI must confirm at least one brain lesion with a diameter ≥5 mm.\n6. No prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC. Patients who underwent radical surgery, chemoradiotherapy, or adjuvant therapy (chemotherapy or radiotherapy) for early-stage NSCLC may be included if their disease recurred or metastasized after treatment, provided the interval from the last treatment to initial tumor recurrence exceeds 6 months.\n7. Normal function of major organs, with the following criteria: Hematology (without transfusion or hematopoietic stimulating factors within 14 days): Hemoglobin (HB) ≥ 90 g\u002FL. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹\u002FL. Platelets (PLT) ≥ 80 × 10⁹\u002FL. Biochemistry: Total bilirubin (TBIL) \\\u003C 1.5 × upper limit of normal (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C 2.5 × ULN (if liver metastases are present, ALT and AST \\\u003C 5 × ULN). Creatinine (Cr) ≤ 1.25 × ULN or creatinine clearance rate (CCr) ≥ 45 mL\u002Fmin (using the Cockcroft-Gault formula). Proteinuria \\\u003C 2+ (if baseline proteinuria ≥ 2+, a 24-hour urine protein quantification ≤ 1 g is required). International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%) as assessed by Doppler ultrasound.\n8. Women of childbearing potential must agree to use effective contraception (e.g., intrauterine devices, oral contraceptives, or condoms) during the study and for 6 months after its completion. Negative serum or urine pregnancy test within 7 days prior to enrollment and non-lactating status are required. Male participants must agree to use contraception during the study and for 6 months afterward.\n9. Participants must voluntarily consent to participate in the study, sign an informed consent form, and demonstrate good compliance.\n\nExclusion Criteria:\n\n1. Active Bleeding with Brain and\u002For Leptomeningeal Metastases\n2. Includes therapies with agents such as bevacizumab, endurance, or anlotinib.\n3. ≥ Grade 2 toxicity (NCI-CTCAE v4.03) related to prior treatments not resolved at the start of study treatment (excluding alopecia and Grade 2 neurotoxicity caused by platinum agents).\n4. Includes uncontrolled nausea\u002Fvomiting, inability to swallow, gastrointestinal resection, chronic diarrhea, or intestinal obstruction\n5. Prior whole-brain radiotherapy (WBRT). Radiotherapy involving \\>30% of bone marrow or extensive radiation within 4 weeks before the first dose (palliative radiotherapy for non-brain metastases, such as bone metastases, is exempt).\n6. Poorly controlled hypertension (defined as blood pressure ≥160\u002F100 mmHg despite optimal antihypertensive therapy). Cardiac criteria, including: QTcF ≥ 470 msec (average of three ECGs, corrected using Fredericia's formula) at rest. Clinically significant arrhythmias, conduction abnormalities, or ECG changes (e.g., complete left bundle branch block, third-degree AV block, second-degree AV block, PR interval ≥250 msec). Factors increasing risk of QT prolongation or arrhythmias, such as NYHA Class III-IV heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or use of QT-prolonging medications. Active or uncontrolled severe infections. Liver disease, including cirrhosis, decompensated liver disease, or chronic active hepatitis. Poorly controlled diabetes (fasting blood glucose \\>10 mmol\u002FL). Urinalysis showing ≥2+ proteinuria, confirmed by 24-hour urine protein quantification \\>1.0 g.\n7. Presence of unhealed wounds or fractures.\n8. NCI-CTCAE \\> Grade 1 pulmonary bleeding within 4 weeks before enrollment. NCI-CTCAE \\> Grade 2 bleeding at other sites within 4 weeks before enrollment. Bleeding tendencies (e.g., active gastrointestinal ulcers) or patients on thrombolytic or anticoagulant therapy (e.g., warfarin, heparin, or similar agents).\n9. History of arterial\u002Fvenous thrombosis within 12 months before enrollment, including stroke (e.g., transient ischemic attack, cerebral hemorrhage, or infarction), deep vein thrombosis, or pulmonary embolism.\n10. Clinically significant hemoptysis (\\>50 mL\u002Fday) within 3 months before enrollment. Severe bleeding symptoms or conditions such as gastrointestinal bleeding, bleeding gastric ulcers, stool occult blood ≥2+, or vasculitis.\n11. History of interstitial lung disease, drug-induced interstitial lung disease, steroid-requiring radiation pneumonitis, or clinically active interstitial lung disease.\n12. History of substance abuse or uncontrolled psychiatric disorders.\n13. Poorly controlled pleural or ascitic effusions despite symptomatic treatment, causing Grade ≥2 respiratory syndrome (≥CTCAE Grade 2).\n14. Known active infections, including: Active hepatitis B (HBsAg positive and HBV-DNA ≥ 2 × 10³ IU\u002FmL during screening). Hepatitis C (HCV-Ab positive and HCV-RNA positive during screening). Active tuberculosis (evidence of active infection within 1 year). Syphilis (both specific and non-specific antibodies positive). HIV infection (HIV antibody positive). Active infections are not routinely screened unless clinically indicated.\n15. Severe diseases or conditions deemed to pose risks to patient safety or impede study completion.\n16. Severe diseases or conditions deemed to pose risks to patient safety or impede study completion.\n17. Prior allogeneic bone marrow transplantation.\n18. Prior allogeneic bone marrow transplantation. 19)Any other condition deemed unsuitable for the study by the investigator. 20)Major surgery within 28 days before the first dose (defined as surgeries requiring at least 3 weeks of recovery before study treatment).","15 Years",{"count":187,"type":20},70,[77],"This study evaluates the safety and efficacy of Befotertinib combined with Bevacizumab as a first-line treatment for patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) accompanied by brain or leptomeningeal metastases. It is a single-arm, open-label, prospective Phase II clinical trial aiming to explore the potential benefits of this combination therapy in improving intracranial progression-free survival (iPFS) and overall survival (OS). Patients will receive Befotertinib daily and Bevacizumab every three weeks until disease progression, intolerable toxicity, or withdrawal of consent. The study seeks to address the unmet need for effective treatments in this challenging patient population.",[191,192,193,26,194],"Non-small Cell Lung Cancer (NSCLC)","EGFR Mutation-Positive Lung Cancer","Brain Metastases","Intracranial Tumor Progression","2024-12-08",{"date":197,"type":31},"2024-12-11",{"date":199,"type":31},"2024-09-04",{"date":201,"type":20},"2028-02-01",{"name":203,"class":38},"Li-kun Chen"]