[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"treatment-failure\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:treatment-failure":31},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,45,63],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100632497","phase-2-regorafenib-after-treatment-failure-of-first-line-immune-checkpoint-inhibitor-treatment-in-advanced-hepatocellular-carcinoma-patients-100632497",false,"NCT07514455","Regorafenib After Treatment Failure of First Line Immune Checkpoint Inhibitor Treatment in Advanced Hepatocellular Carcinoma Patients","Regorafenib After Failure of First-Line Immune Checkpoint Inhibitor-Based Combination Therapy in Child-Pugh B Patients With HCC: A Phase 2 RECOMEND Trial","RECOMEND","Inclusion Criteria:\n\n1. Voluntarily signed written informed consent form.\n2. Age ≥19 years at the time of signing the informed consent form.\n3. Histologically or clinically diagnosed hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines.\n4. Disease progression or treatment discontinuation due to toxicity during first-line immune checkpoint inhibitor-based combination therapy (atezolizumab plus bevacizumab, durvalumab plus tremelimumab, or nivolumab plus ipilimumab).\n5. At least one measurable target lesion according to RECIST v1.1.\n6. Child-Pugh score B (7-8).Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n7. Adequate hematologic and end-organ function defined by the following laboratory results obtained within 14 days prior to the test (or enrollment):\n\n   * Hemoglobin ≥ 8.5 g\u002FdL\n   * Absolute Neutrophil Count (ANC) ≥1,200\u002Fmm³\n   * Platelet count ≥60,000\u002FµL\n   * Total bilirubin \\\u003C 3.5 mg\u002FdL\n   * Serum albumin ≥2.5 g\u002FdL\n   * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤7 times upper limit of normal (ULN)\n   * Prothrombin time (INR ≤1.8 times ULN)\n   * Serum creatinine ≤2.0 times ULN or calculated creatinine clearance ≥40 mL\u002Fmin (using the Cockcroft-Gault equation)\n\n10\\) Virologic status of hepatitis confirmed and documented by HBV and HCV screening tests.Patients with HBV or HCV infection must receive antiviral therapy according to institutional guidelines.\n\n11\\) Women of childbearing potential must agree to remain abstinent or use effective contraception (with an annual failure rate of \\\u003C 1%) from the time of signing informed consent until at least 6 months after the last dose of the study drug.Male participants must agree to remain abstinent or use effective contraception (with an annual failure rate of \\\u003C 1%) and refrain from sperm donation from the time of signing informed consent until at least 6 months after the last dose of the study drug.\n\nExclusion Criteria:\n\n1. ALBI (Albumin-Bilirubin) grade 3.\n2. Fibrolamellar carcinoma or sarcomatoid carcinoma.\n3. Prior treatment with regorafenib.\n4. Within 2 weeks since the last administration of an immune checkpoint inhibitor.\n5. Receipt of any other systemic or locoregional therapy after the failure of first-line immune checkpoint inhibitor-based therapy.\n6. History of allogeneic stem cell transplantation or solid organ transplantation.\n7. Active brain metastases or leptomeningeal metastases.\n8. History of malignancy other than hepatocellular carcinoma (HCC) within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year survival rate \\> 90%).\n9. Severe cardiovascular disease within 3 months prior to the start of study therapy (e.g., New York Heart Association \\[NYHA\\] Class II or higher heart disease, myocardial infarction, or cerebrovascular accident); unstable arrhythmia or unstable angina; history of gastrointestinal perforation, fistula, or intra-abdominal abscess within 6 months prior to the start of study therapy; active gastrointestinal disease with a high risk of bleeding or perforation (e.g., peptic ulcer, inflammatory bowel disease, diverticulitis, cholecystitis, acute pancreatitis); untreated high-risk varices or recent history of variceal bleeding (enrollment is permitted only if at least 28 days have passed since stabilization with standard treatment); prolonged QTc interval (\\> 450 ms for males, \\> 470 ms for females); systolic blood pressure \\> 140 mmHg or diastolic blood pressure \\> 90 mmHg despite optimal medical therapy; or other significant medical conditions or abnormal findings that, in the opinion of the investigator, may increase the risk associated with study participation.\n10. Female participants who are pregnant or breastfeeding, or male or female participants of reproductive potential who are unwilling to use effective contraception from screening until 6 months after the last dose of the study drug.\n11. Participants deemed by the investigator to be unlikely to comply with study procedures, restrictions, and requirements.\n12. Patients who have received locoregional therapy (e.g., radiofrequency ablation \\[RFA\\], microwave ablation \\[MWA\\], transarterial chemoembolization \\[TACE\\], transarterial radioembolization \\[TARE\\], transarterial embolization \\[TAE\\], radiation therapy, etc.) after the discontinuation of immune checkpoint inhibitor-based combination therapy.","ALL","19 Years","80 Years",{"count":21,"type":22},20,"ESTIMATED","INTERVENTIONAL",[25],"PHASE2","Immune checkpoint inhibitor (ICI)-based regimens (atezolizumab+bevacizumab, durvalumab+tremelimumab, nivolumab+ipilimumab) are now a first-line standard for advanced hepatocellular carcinoma (HCC). For Child-Pugh (CP) A patients, regorafenib, cabozantinib, and ramucirumab are approved second-line agents, but there is no approved second-line systemic therapy for CP-B. In CP-B historical controls treated with best supportive care, median progression free survival (PFS) was \\~1.4 months in a REACH trial subgroup analysis and \\~1.9 months in a CELESTIAL trial subgroup analysis. Regorafenib demonstrated benefit as a post-sorafenib second-line therapy in CP-A patients in the RESORCE trial, but prospective evidence in CP-B is lacking. A multicenter retrospective study of CP-B patients receiving second-line regorafenib after sorafenib reported a median PFS of 1.8 months, and prospective data after ICI-based first-line therapy are not available.\n\nThis study will evaluate the efficacy and safety of regorafenib as second-line therapy in CP-B patients with disease progression after first-line ICI-based treatment. The primary objective is to demonstrate superiority over historical controls, with PFS as the primary endpoint.\n\nAfter written informed consent, all participants will receive regorafenib. Regorafenib will be administered at 120 mg orally once daily at the same time each day, after a meal with water, for 3 consecutive weeks followed by 1 week off (4-week cycle). Treatment must start within 3 days after screening and will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first. After treatment discontinuation, patients will be followed every 12 week (+\u002F-7 days) for survival status and subsequent anticancer therapies, and survival follow-up will continue for at least 12 months after enrollment of the last participant.",[28,29,30,31],"Carcinoma, Hepatocellular","Hepatic Insufficien","Disease Progression","Treatment Failure","NOT_YET_RECRUITING","2026-03-30",{"date":35,"type":36},"2026-04-07","ACTUAL",{"date":38,"type":22},"2026-03-15",{"date":40,"type":22},"2028-06-30",{"name":42,"class":43},"Ju Hyun Shim","OTHER",1,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":51,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":53,"targetDuration":4,"studyType":23,"phases":55,"briefSummary":56,"conditions":57,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":59,"startDateStruct":60,"completionDateStruct":61,"leadSponsor":62,"locationsCount":44},"100632495","phase-2-regorafenib-after-failure-of-lenvatinib-in-patients-with-unresectable-hcc-the-relevant-hcc-trial-100632495","NCT07514429","Regorafenib After Failure of Lenvatinib in Patients With Unresectable HCC: The RELEVANT-HCC Trial","Regorafenib After Failure of Lenvatinib in Patients With Unresectable HCC: A Phase 2 RELEVANT-HCC Trial","RELEVANT-HCC","Inclusion Criteria:\n\n1. Signed informed consent form.\n2. Age ≥ 19 years at the time of signing the informed consent form.\n3. Diagnosis of hepatocellular carcinoma (HCC) confirmed histologically or clinically according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines.\n4. Patients with unresectable HCC who have experienced disease progression or treatment discontinuation due to toxicity during prior treatment with lenvatinib.\n5. Presence of at least one measurable target lesion according to RECIST v1.1.\n6. Child-Pugh classification A or B7 (score 7).\n7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n8. Adequate hematologic and end-organ function defined by the following laboratory test results obtained within 14 days prior to testing (or enrollment):\n\n   * Hemoglobin ≥ 8.5 g\u002FdL\n   * Absolute neutrophil count (ANC) ≥ 1,200\u002Fmm³\n   * Platelet count ≥ 60,000\u002FμL\n   * Total bilirubin \\\u003C 3.5 mg\u002FdL\n   * Serum albumin ≥ 2.5 g\u002FdL\n   * AST and ALT ≤ 7 × upper limit of normal (ULN)\n   * Prothrombin time (INR ≤ 1.8 × ULN)\n   * Serum creatinine ≤ 2.0 × ULN or calculated creatinine clearance ≥ 40 mL\u002Fmin (Cockcroft-Gault equation)\n9. Virological status of hepatitis confirmed and recorded through HBV and HCV screening.\n\n   * Participants with HBV or HCV infection must be receiving antiviral therapy according to institutional guidelines.\n10. Women of childbearing potential must agree to maintain abstinence or use effective contraception (with an annual failure rate of \\\u003C 1%) from the time of signing the informed consent until at least 6 months after the last dose of the study drug. Male participants must agree to maintain abstinence or use effective contraception (with an annual failure rate of \\\u003C 1%) and refrain from sperm donation from the time of signing the informed consent until at least 6 months after the last dose of the study drug.\n\nExclusion Criteria:\n\n1. Albumin-bilirubin (ALBI) grade 3.\n2. Fibrolamellar carcinoma or sarcomatoid carcinoma.\n3. Prior treatment with regorafenib.\n4. History of allogeneic stem cell transplantation or solid organ transplantation.\n5. Active brain metastases or leptomeningeal metastases.\n6. History of malignancy other than hepatocellular carcinoma (HCC) within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year survival rate \\> 90%).\n7. Severe cardiovascular disease within 3 months prior to the start of study therapy (e.g., New York Heart Association \\[NYHA\\] Class II or higher heart disease, myocardial infarction, or cerebrovascular accident); uncontrolled serious medical comorbidities, including unstable arrhythmia or unstable angina; or other significant medical conditions or abnormal findings that, in the opinion of the investigator, may increase the risk associated with study participation.\n8. Female participants who are pregnant or breastfeeding, or male or female participants of reproductive potential who are unwilling to use effective contraception from screening until 6 months after the last dose of the study drug.\n9. Participants deemed by the investigator to be unlikely to comply with study procedures, restrictions, and requirements.\n10. Patients who have received locoregional therapy (e.g., radiofrequency ablation \\[RFA\\], microwave ablation \\[MWA\\], transarterial chemoembolization \\[TACE\\], transarterial radioembolization \\[TARE\\], transarterial embolization \\[TAE\\], radiation therapy, etc.) after discontinuation of lenvatinib treatment.",{"count":54,"type":22},24,[25],"The purpose of this clinical trial is to evaluate the efficacy and safety of regorafenib as a subsequent therapy for patients with hepatocellular carcinoma (HCC) who have failed prior lenvatinib treatment. This investigational study aims to assess the therapeutic benefits and safety profile of regorafenib in patients whose disease has progressed following the use of lenvatinib, a targeted therapy for hepatocellular carcinoma",[28,58,31],"Lenvatinib",{"date":35,"type":36},{"date":38,"type":22},{"date":40,"type":22},{"name":42,"class":43},{"id":64,"slug":65,"hasResults":11,"nctId":66,"briefTitle":67,"officialTitle":68,"acronym":69,"eligibilityCriteria":70,"healthyVolunteers":11,"sex":17,"minAge":71,"maxAge":72,"enrollmentInfo":73,"targetDuration":4,"studyType":75,"phases":4,"briefSummary":76,"conditions":77,"keywords":83,"overallStatus":99,"whyStopped":4,"lastUpdateSubmitDate":100,"lastUpdatePostDateStruct":101,"startDateStruct":103,"completionDateStruct":105,"leadSponsor":107,"locationsCount":109},"100571207","genomic-and-methylation-markers-in-sclc-and-lcnec-for-chemo-immunotherapy-resistance-prediction-stratus-100571207","NCT06717243","Genomic and Methylation Markers in SCLC and LCNEC for Chemo-Immunotherapy Resistance Prediction (STRATUS)","A Prospective Observational Study on Genomic and Methylation Signatures in Patients with Extensive-Stage Small Cell Lung Cancer and Metastatic Large Cell Neuroendocrine Carcinoma Undergoing Chemo-Immunotherapy","STRATUS","Inclusion Criteria:\n\n* Age: Adults aged 18-85 years.\n* Histologically confirmed locally advanced extensive-stage small cell lung cancer (ES-SCLC).\n* Histologically confirmed locally advanced or metastatic large cell neuroendocrine carcinoma (LCNEC).\n* Treatment Plan: Eligible patients must be initiating standard-of-care chemo-immunotherapy, including platinum-based chemotherapy (cisplatin or carboplatin) combined with immune checkpoint inhibitors (atezolizumab or durvalumab).\n* Measurable Disease: At least one measurable or evaluable lesion as defined by RECIST 1.1 criteria.\n* Baseline Biospecimen Availability: Patients must agree to provide baseline blood and tumor biopsy samples for molecular and genomic analyses.\n* Treatment Naïve for Study Indication: Patients should not have received prior systemic therapy for ES-SCLC or LCNEC.\n* Life Expectancy: Estimated life expectancy of at least 3 months, as determined by the treating physician.\n* Follow-Up Commitment: Willingness to attend scheduled follow-up visits and provide additional biospecimens (blood and\u002For tissue) during treatment and at progression.\n* Performance Status: ECOG performance status of 0-2.\n* Organ Function: Adequate hematologic, renal, and hepatic function as per the treating physician's discretion.\n* Consent: Ability and willingness to provide written informed consent for participation in the study and collection of biospecimens (e.g., blood and tumor tissue).\n* Compliance with Study Protocol: Demonstrated ability and willingness to comply with all study-related procedures, including biospecimen collection and follow-up visits.\n* Non-Pregnant and Non-Lactating: Women of childbearing potential must have a negative pregnancy test at baseline and agree to use effective contraception during the study period.\n* Immunotherapy Eligibility: Patients must not have contraindications to immune checkpoint inhibitors (e.g., autoimmune diseases requiring systemic immunosuppressive therapy).\n* Platinum-Based Therapy Tolerance: Patients must be deemed medically fit to receive platinum-based chemotherapy (cisplatin or carboplatin) as determined by the treating physician.\n* No Active Infections: Patients must not have active, uncontrolled infections, including but not limited to tuberculosis, hepatitis B, hepatitis C, or HIV.\n* Psychosocial Stability: Patients must have adequate psychosocial support and the mental capacity to understand and provide informed consent for participation in the study.\n* Stable Brain Metastases: Patients with brain metastases are eligible if the metastases have been treated (e.g., surgery or radiotherapy) and are stable for at least 4 weeks prior to enrollment, as confirmed by imaging.\n* Steroid Use for Brain Metastases: Patients requiring corticosteroids for brain metastases are eligible only if they are on a stable or tapering dose equivalent to ≤10 mg\u002Fday of prednisone for at least 2 weeks prior to enrollment.\n\nExclusion Criteria:\n\n* Uncontrolled Brain Metastases: Patients with untreated or progressive brain metastases causing significant neurological symptoms.\n* Concurrent Malignancies: Presence of any active malignancy other than ES-SCLC or LCNEC within the past 3 years, except for treated non-melanoma skin cancer or in situ cervical carcinoma.\n* Previous Systemic Therapy: Prior systemic chemotherapy or immunotherapy for ES-SCLC or LCNEC.\n* Severe Comorbidities: Significant comorbidities, such as uncontrolled cardiovascular, respiratory, or autoimmune diseases, that could interfere with study participation or treatment.\n* Active Infection: Patients with active infections requiring systemic therapy, including tuberculosis, hepatitis B or C, or HIV.\n* Pregnancy or Lactation: Pregnant or lactating women, or women of childbearing potential who are not using effective contraception.\n* Immunosuppressive Therapy: Patients requiring systemic immunosuppressive therapy, including high-dose corticosteroids (equivalent to \\>10 mg\u002Fday prednisone), within 2 weeks prior to enrollment.\n* Severe Allergic Reactions: History of severe hypersensitivity reactions to any component of the planned treatment regimen, including platinum-based chemotherapy or immune checkpoint inhibitors.\n* Life-Threatening Conditions: Life expectancy less than 3 months, as assessed by the treating physician.\n* Inability to Comply: Patients unable or unwilling to adhere to study protocols, including biospecimen collection and follow-up visits.","18 Years","85 Years",{"count":74,"type":22},111,"OBSERVATIONAL","The goal of this observational study is to understand how genomic and epigenetic factors contribute to resistance against chemo-immunotherapy in adults diagnosed with extensive-stage small cell lung cancer (ES-SCLC) or metastatic large cell neuroendocrine carcinoma (LCNEC). Both ES-SCLC and LCNEC are aggressive forms of lung cancer with limited treatment options and poor prognosis. While initial responses to chemo-immunotherapy are often promising, most patients develop resistance within a few months, resulting in disease progression and limited survival. This study seeks to explore the molecular and cellular changes that drive resistance, providing insights that could guide more personalized and effective treatment strategies in the future.\n\nThe study focuses on identifying genomic and methylation signatures, as well as analyzing circulating tumor cells (CTCs) and tumor DNA (ctDNA), to better understand the mechanisms of resistance. By collecting and analyzing these biomarkers over time, researchers aim to identify patterns that distinguish patients who benefit long-term from therapy from those who experience early resistance. These findings may pave the way for new diagnostic tools and therapies to predict and overcome resistance to chemo-immunotherapy.\n\nThe main questions this study seeks to answer are:\n\nAre there specific genomic or methylation patterns that predict resistance to chemo-immunotherapy in ES-SCLC and LCNEC? How are circulating tumor cells (CTCs) and tumor DNA (ctDNA) associated with disease progression, treatment response, and survival? What molecular differences exist between patients who respond long-term and those who develop resistance early in their treatment?\n\nParticipants will:\n\nProvide blood and tumor tissue samples before treatment to establish baseline molecular profiles.\n\nUndergo follow-up visits every 9 weeks during treatment, where additional blood samples and imaging tests will be collected to monitor disease progression and treatment response.\n\nOptionally provide tissue samples through re-biopsy if the disease progresses, enabling researchers to compare changes in tumor biology over time.\n\nAll blood and tissue samples will be de-identified and securely stored for genomic and epigenetic analyses. Blood samples will be examined for circulating tumor cells and tumor DNA, while tumor tissue samples will undergo in-depth genomic and methylation profiling. Researchers will use advanced molecular and bioinformatics techniques to uncover specific patterns associated with resistance, aiming to improve current treatment strategies and develop more precise therapies.\n\nThe study will analyze data from patients over three years, encompassing various stages of treatment and disease progression. By examining longitudinal samples, the study aims to capture the dynamic changes that occur in the tumor microenvironment and how these relate to treatment outcomes.\n\nThis research is particularly important because current treatment options for ES-SCLC and LCNEC are limited, and there are no established methods to predict which patients will respond to chemo-immunotherapy. Identifying biomarkers of resistance could transform clinical care, allowing oncologists to tailor treatments to individual patients' molecular profiles and improve survival outcomes.\n\nUltimately, the findings from this study could lead to the development of new biomarkers for resistance, improve early detection of treatment failure, and provide the foundation for novel therapies targeting resistant cancer cells. By addressing a critical gap in the understanding of resistance mechanisms, the STRATUS trial has the potential to significantly advance the field of personalized oncology.",[78,79,31,80,81,82],"Small Cell Lung Cancer","Large Cell Neuroendocrine (NE) Tumors","Biomarkers \u002F Blood","Biomarkers","Immunotherapy",[84,85,86,87,88,89,90,91,92,93,94,95,96,97,98],"Small Cell Lung Cancer (SCLC)","Large Cell Neuroendocrine Carcinoma (LCNEC)","Chemo-Immunotherapy","Treatment Resistance","Circulating Tumor Cells (CTCs)","Circulating Tumor DNA (ctDNA)","Liquid Biopsy","Genomic Profiling","Epigenetics","Biomarker Discovery","Lung Cancer","Molecular Signatures","Clonal Evolution","Personalized Oncology","Cancer Immunotherapy","RECRUITING","2025-03-18",{"date":102,"type":36},"2025-03-19",{"date":104,"type":36},"2025-02-20",{"date":106,"type":22},"2028-12-01",{"name":108,"class":43},"Oncology Center of Biochemical Education And Research",2]