[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":484},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,17,0,[8,51,83,104,133,155,187,214,244,277,303,329,360,381,403,430,459],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":32,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":39,"lastUpdatePostDateStruct":40,"startDateStruct":43,"completionDateStruct":45,"leadSponsor":47,"locationsCount":50},"100606496","phase-2-zanidatamab-in-combination-with-pembrolizumab-and-chemotherapy-in-her2-and-pd-l1-positive-metastatic-gastroesophageal-adenocarcinoma-gea-patients-100606496",false,"NCT07176312","Zanidatamab in Combination With Pembrolizumab and Chemotherapy in HER2 and PD-L1 Positive Metastatic Gastroesophageal Adenocarcinoma (GEA) Patients","- ZANGEA - Phase II Study of Zanidatamab in Combination With Pembrolizumab and Chemotherapy in HER2 and PD-L1 Positive Metastatic Gastroesophageal Adenocarcinoma (GEA) Patients","ZANGEA","Inclusion Criteria:\n\n* Patient\\* has signed and dated a written informed consent form in accordance with regulatory and institutional guidelines and approved by an institutional Review Board \u002F Independent Ethics Committee. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.\n* Patient is, in the investigator's judgement, willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.\n* Patient is ≥ 18 years of age at time of signing the written informed consent.\n* Patient has been diagnosed with histologically confirmed unresectable advanced\u002Fmetastatic HER2-positive (defined as IHC 3+ or IHC 2+ with ISH+) and PD-L1-positive (combined positive score CPS ≥ 1) gastroesophageal adenocarcinoma per local standard assessment of new or archival tumor tissue. Results of local HER2 and PD-L1 assessment will be retrospectively confirmed by central pathological re-assessment.\n\nNote: In case of metachronous metastases, particularly in case of prior treatment with PD-(L)1-antibodies, a fresh re-biopsy should be performed for immunohistochemistry testing (local pathology), if feasible.\n\n* Patient has assessable disease (measurable or non-measurable) per RECIST v1.1.\n* Patient did not receive previous palliative treatment. Prior adjuvant or neoadjuvant chemotherapy, immunotherapy, radiotherapy and\u002For chemoradiotherapy (but not anti HER2-targeted treatment) are permitted as long as the last administration of the last regimen (whichever was given last) occurred at least 6 months prior to enrolment.\n* Patient has ECOG performance status ≤ 1.\n* Patient has adequate hepatic, renal and hematologic functions:\n\n  1. Absolute number of neutrophils (ANC) ≥ 1.5 x 10\\^9\u002FL\n  2. Platelets ≥ 100x10\\^3\u002FµL\n  3. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (measured by 24 h urine) ≥ 30 mL\u002Fmin (i.e., if serum creatinine level is \\> 1.5 x upper limit of normal (ULN), then a 24-hour urine test must be performed to check the creatinine clearance to be determined.\n  4. AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN if liver metastases are present)\n  5. Total Bilirubin ≤ 1.5 x ULN (or \\\u003C 3.0 x ULN in case of prior liver involvement or Gilbert's Syndrome)\n* Patient has adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).\n* Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of human chorionic gonadotrophin \\[hCG\\]) within 7 days prior to the start of study drug. Women must not be breastfeeding. WOCBP must use a highly effective method(s) of contraception during the treatment period and for 4 months after last dose of zanidatamab and\u002For pembrolizumab, or 6 months after the last dose of chemotherapy, whichever occurs last. Males who are sexually active with WOCBP must agree to remain abstinent or follow instructions for method(s) of contraception during the treatment and for 4 months after the last dose of zanidatamab and\u002For pembrolizumab, or 6 months after the last dose of chemotherapy, whichever occurs last. In addition, male subjects must be willing to refrain from sperm donation during this time.\n\n  * There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.\n\nExclusion Criteria:\n\n* Patient has any known contraindication including allergy or hypersensitivity to the trial drugs or any constituent of the products as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies.\n* Patient received prior anti HER2-targeted treatment for GEA.\n* Patient has malignancies other than the disease under study within 5 years prior to inclusion, except for 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* Patient has untreated known CNS metastases. Patient is eligible, if previous CNS metastases are adequately treated and patient has neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for ≥ 2 weeks prior to enrolment, and did not receive corticosteroids, or is on a stable or decreasing dose of \\\u003C 10 mg daily prednisone (or equivalent) for ≥ 2 weeks prior to inclusion.\n* Patient has abnormal baseline left ventricular ejection fraction (LVEF \\\u003C 50 %), assessed by echocardiogram, multigated acquisition (MUGA) scan, or cardiac magnetic resonance imaging (MRI) scan.\n* Patient has active, known, or suspected autoimmune disease. Exception: Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the medical expert\u002Fsponsor be consulted prior to signing informed consent.\n* Patient has a condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of trial drug administration. Inhaled or topical steroids, and adrenal replacement doses \\> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.\n* Patient has persisting toxicity related to prior therapy (NCI CTCAE v.5.0 Grade \\> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.\n* Patient has any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with trial participation, trial drug administration, or would impair the ability of the patient to receive trial drug.\n* Patient has significant acute or chronic infections including, among others:\n* Any positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).\n* Any positive test result for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.\n* Patient has history of allogeneic tissue \u002F solid organ transplant.\n* Patient has been incarcerated or involuntarily institutionalized by court order or by the authorities \\[§ 40 Abs. 1 S. 3 Nr. 4 AMG\\].\n* Patient is unable to consent because he\u002Fshe does not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts \\[§ 40 Abs. 1 S. 3 Nr. 3a AMG\\].\n* Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the trial medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of trial results.\n* Patient currently participates in any other interventional clinical study within 30 days before the first administration of the investigational product or at any time during the trial, unless it is an observational (non-interventional) study, or during the follow-up period of an interventional study with last dose of investigational product ≥28 days prior to enrolment in this trial.\n* Patient has a known complete absence of dihydropyrimidine dehydrogenase (DPD) activity or use of any medications known to inhibit DPD (including brivudine, sorivudine and analogs) within 4 weeks prior to enrolment.\n* Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of trial treatment.","ALL","18 Years",{"count":20,"type":21},80,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","The ZANGEA trial is a open-label, single arm, multicenter phase II trial assessing the efficacy of zanidatamab in combination with pembrolizumab and chemotherapy in patients with metastatic gastroesophageal adenocarcinoma (GEA). The patients need to be previously untreated in the palliative setting and tested positive for HER2 and PD-L1.",[27,28,29,30,31],"Gastroesophageal Adenocarcinoma","First Line Therapy","HER2 + Gastric Cancer","PDL-1","Metastases",[33,34,35,36,37],"GEA","Gastroesophageal adenocarcinoma","first line therapy","HER2-positive","PD-L1 positive","RECRUITING","2026-06-29",{"date":41,"type":42},"2026-06-30","ACTUAL",{"date":44,"type":42},"2026-01-16",{"date":46,"type":21},"2029-03",{"name":48,"class":49},"Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest","OTHER",20,{"id":52,"slug":53,"hasResults":11,"nctId":54,"briefTitle":55,"officialTitle":56,"acronym":57,"eligibilityCriteria":58,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":59,"targetDuration":4,"studyType":22,"phases":61,"briefSummary":62,"conditions":63,"keywords":67,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":74,"lastUpdatePostDateStruct":75,"startDateStruct":77,"completionDateStruct":79,"leadSponsor":81,"locationsCount":82},"100622713","phase-2-neoadjuvant-merkel-cell-carcinoma-therapy-tx-with-the-pd-1-inhibitor-cemiplimab-100622713","NCT07387198","Neoadjuvant Merkel Cell Carcinoma Therapy (Tx) With the PD-1 Inhibitor Cemiplimab","Neoadjuvant Merkel Cell Carcinoma Therapy (Tx) With the PD-1 Inhibitor Cemiplimab - A Randomized, Double-blind, Placebo-controlled, Non-comparative Phase II Study","NeoMatryx","Inclusion criteria\n\n1. Patient has signed informed written consent.\n2. Patients is 18 years and older at time of signing of written informed consent\n3. Patient has diagnosis of Merkel cell carcinoma in clinical stage II, or in stage I with minimum diameter of 1 cm, with primary tumor already removed and a planned sentinel lymph nodes biopsy still pending.\n4. Patient has ECOG performance status 0-2.\n5. Patients has adequate laboratory parameters particularly for the blood count, renal and liver function parameters.\n\n   1. Absolute number of neutrophils ≥ 1.5 x 109\u002FL\n   2. Platelets ≥ 75 x 109\u002FL\n   3. Hemoglobin ≥ 9 g\u002FdL\n   4. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with Gilbert´s Disease and total bilirubin up to 3x ULN may be eligible after approval from trial's medical expert)\n   5. AST (SGOT) and ALT (SGPT) ≤ 3x ULN\n   6. AP ≤ 2.5x ULN\n   7. Serum creatinine ≤ 2x ULN or creatinine clearance ≥ 40 mL\u002Fmin\n6. Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year during the treatment period and for at least 6 months after the last dose of Cemiplimab. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.\n7. Patient must be willing to allow translational work-up of tissue samples (PT, sentinel lymph node biopsy).\n\nExclusion criteria\n\n1. Patient has prior sentinel lymph node removal for the current MCC.\n2. Patients received prior treatment with immunotherapy (such as PD-1\u002FPD-L1 or CTL4) or any other systemic anti-tumor (MCC) therapy (incl. investigational therapies)\n3. Patient has active or a history of hematological neoplasms including chronic lymphocytic leukemia (CLL), irrespective if these require treatment or not.\n4. Patient had prior organ transplantation including allogenic stem-cell transplantation.\n5. Patient receives immunosuppressive concomitant medication, EXCEPT for the following:\n\n   i. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection).\n\n   ii. Systemic corticosteroids at physiologic doses ≤ 10 mg\u002Fday of prednisone or equivalent.\n\n   iii. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).\n6. Patient has known hypersensitivity to any component of the Cemiplimab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.\n7. Patient has active autoimmune or inflammatory disorders.\n8. Patient has history of interstitial lung disease.\n9. Patient has active infection requiring systemic therapy.\n10. Patient has Active infection requiring systemic therapy, including uncontrolled HIV, HBV and HCV infection or diagnosis of immunodeficiency.\n\n    NOTE: Patients are eligible if:\n    * Patients have controlled HIV infection with CD4 counts is \\> 350 cells\u002FμL and viral load is undetectable \\[HIV RNA PCR\\]. Patients with controlled HIV infection must be monitored per local standards during the trial.\n    * Patients positive for HBV surface antigen have controlled HBV infection receiving anti-viral therapy and with undetectable serum viral load \\[HBV DNA PCR\\]. Patients with controlled infection must undergo periodic monitoring of HBV DNA and p must remain on anti-viral therapy for at least 6 months after last dose of Cemiplimab.\n    * Patients positive for HCV antibody have controlled HCV infection with undetectable viral load \\[HCV RNA PCR\\].\n11. Patent received vaccination with any live vaccine (e.g., intranasal flu vaccine) within 4 weeks before the first dose of Cemiplimab or planned vaccination with live vaccine during the trial\n12. Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum β-HCG pregnancy test result within 7 days prior to initiation of study treatment.\n13. Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results.\n14. Patient has known substance abuse or other psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results\n15. Patient is legally incapacitated or has limited legal capacity",{"count":60,"type":21},135,[24],"The study is a randomized, double blind, placebo-controlled, non-comparative phase II trial that investigates the efficacy of neoadjuvant anti-PD-1 antibody Cemiplimab treatment in patients with clinical stage I or II Merkel cell carcinoma who have have undergone primary tumour excision and are pending sentinel lymph node biopsy.",[64,65,66],"Merkel Cell Carcinoma, Stage I","Merkel Cell Carcinoma, Stage II","Neoadjuvant Immunotherapy",[68,69,70,71,72,73],"merkel cell carcinoma","sentinel lymph node","PD-1 antibody","skin cancer","Cemiplimab","MCC","2026-06-18",{"date":76,"type":42},"2026-06-22",{"date":78,"type":42},"2026-05-29",{"date":80,"type":21},"2031-07-31",{"name":48,"class":49},14,{"id":84,"slug":85,"hasResults":11,"nctId":86,"briefTitle":87,"officialTitle":88,"acronym":4,"eligibilityCriteria":89,"healthyVolunteers":11,"sex":90,"minAge":18,"maxAge":4,"enrollmentInfo":91,"targetDuration":4,"studyType":22,"phases":93,"briefSummary":94,"conditions":95,"keywords":4,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":74,"lastUpdatePostDateStruct":97,"startDateStruct":98,"completionDateStruct":100,"leadSponsor":102,"locationsCount":103},"100601403","phase-2-depeca-1---a-phase-ii-study-to-evaluate-a-first-line-systemic-therapy-with-enfortumab-vedotin-plus-avelumab-for-advanced-and-metastatic-penile-carcinoma-100601403","NCT07110038","DEPECA-1 - A Phase II Study to Evaluate a First-line Systemic Therapy With Enfortumab Vedotin Plus Avelumab for Advanced and Metastatic Penile Carcinoma","DEPECA-1 - DEfeating PEnile Cancer 1 - A Phase II Study to Evaluate a First-line Systemic Therapy With Enfortumab Vedotin Plus Avelumab for Advanced and Metastatic Penile Carcinoma","Inclusion Criteria:\n\n1. Patient has ability to understand and the willingness to sign a written informed consent.\n2. Patient is ≥ 18 years of age at time of signing the written informed consent.\n3. Male patients with histologically confirmed diagnosis of penile squamous cell carcinoma.\n4. Patients must be considered non-eligible for curative surgical management. Eligibility for trial inclusion should be based on the presence of either distant metastatic disease (M1) or at least one of the following scenarios based on the UICC\u002FAJCC 8th edition TNM clinical and pathological classification of penile cancer:\n\n   1. Stage 3 (cT3) disease with a single lymph node involved (N1).\n   2. Stage 4 disease (cT4).\n   3. Any T stage with either N2 (involvement of multiple or bilateral inguinal nodes) or N3 (fixed inguinal nodal mass or pelvic lymphadenopathy) disease. Patients without distant metastases are eligible if multidisciplinary team review concludes that they are unsuitable for curative surgery.\n5. Tumor material (archival or current) is available for local pathology testing (PD-L1, HPV).\n6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.\n7. Measurable disease per RECIST 1.1 criteria.\n8. No prior systemic therapy for metastatic or locally advanced PeCa in the palliative setting. NOTE: (Neo)adjuvant systemic therapy (without IO) is allowed at least 6 months before study enrollment.\n9. Patients has adequate blood count, liver-enzymes, and renal function:\n\n   1. ANC (Absolute neutrophil count) \\> 1,500 cells\u002FμL without the use of hematopoietic growth factors.\n   2. Platelet count ≥ 100 x 109\u002FL (\\>100,000 per mm3).\n   3. Hemoglobin ≥ 9 g\u002FdL.\n   4. Serum total bilirubin ≤ 1.5x institutional upper normal limit (ULN).\n   5. AST (SGOT)\u002FALT (SGPT) ≤ 2.5 x institutional ULN (or ≤ 5 x ULN if liver metastases are present).\n   6. Creatinine clearance ≥ 30 mL\u002Fmin as calculated by the Cockcroft- Gault equation (or local institutional standard method).\n10. No other active malignancy within the past 3 years, except for adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin.\n11. No history of significant cardiovascular disease (e.g., myocardial infarction, unstable angina) within the last 6 months.\n12. Life expectancy of at least 3 months.\n13. Willingness to comply with study requirements, including follow-up visits and procedures.\n14. Patients with female partners of childbearing potential must agree to use an effective method of contraception during the study and for 4 months after the last dose of enfortumab vedotin or for at least 30 days after last avelumab treatment administration, whichever occurs last.\n\nExclusion Criteria:\n\n1. Previous systemic therapy for metastatic or locally advanced PeCa in the palliative setting.\n2. Previous treatment with investigational drugs or devices within 30 days prior to the first dose of trial treatment.\n3. Known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis.\n4. Active, known, or suspected autoimmune disease requiring systemic treatment within the past 2 years. Patients with controlled autoimmune d disease not requiring systemic immunosuppressive treatment including diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases are eligible.\n5. Has ongoing sensory or motor neuropathy Grade 2 or higher.\n6. Has a history of uncontrolled diabetes (HbA1c \\> 8%).\n7. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident\u002Fstroke (\\\u003C 6 months prior to enrollment), myocardial infarction (\\\u003C 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.\n8. Active infection requiring systemic therapy. The following exceptions apply:\n\n   1. Patients with an HIV infection are eligible if they are on effective antiretroviral therapy with undetectable viral load within 6 months, provided there is no expected drug-drug interaction.\n   2. Patients with evidence of chronic HBV infection are eligible if the HBV viral load is undetectable on suppressive therapy (if indicated), and if they have ALT, AST, and total bilirubin levels \\\u003C ULN, and provided there is no expected drug-drug interaction.\n   3. Patients with a history of HCV infection are eligible if they have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load, and if they have ALT, AST, and total bilirubin levels \\\u003C ULN.\n9. History of other malignancies within the past 3 years, with the exception of adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin.\n10. Severe hepatic impairment (Child-Pugh Class C).\n11. Severe renal impairment or requirement for dialysis.\n12. History of keratitis and corneal ulceration in the last two years.\n13. Active pneumonia, pneumonitis or pulmonary fibrosis.\n14. Active tuberculosis.\n15. Known prior severe hypersensitivity to the study drugs or any component of their formulations, known severe hypersensitivity reactions to monoclonal antibodies (NCT CTCAE Grade ≥ 3).\n16. Inability or unwillingness to comply with study requirements, including follow-up visits and procedures.\n17. Inability to provide informed consent.\n18. Use of immunosuppressive medication within 14 days prior to the first dose of study treatment, with the exception of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection), systemic corticosteroids at physiologic doses not to exceed 10 mg\u002Fday of prednisone or equivalent, or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).\n19. Prior organ transplantation including allogenic stem-cell transplantation.\n20. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.\n21. Persisting toxicity related to prior therapy (NCI CTCAE Grade \\> 1); however, alopecia or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.\n22. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.\n23. Patient participated in another interventional clinical study according to Medicines Act within 28 days prior to study enrollment or participation in a clinical study according to Medicines Act at the same time as this study unless it is an observational \u002F non-interventional study or during the follow- up period of an interventional study.","MALE",{"count":92,"type":21},25,[24],"The DEPECA-1 trial is the first systematic Phase II trial to evaluate response and survival to a combination of antibody-drug conjugate enfortumab vedotin plus the PD-L1 inhibitor avelumab in patients with locally advanced and metastatic penile squamous cell carcinoma (PeCa) in the 1st line setting.",[96],"Penile Squamous Cell Carcinoma (PSCC)",{"date":76,"type":42},{"date":99,"type":42},"2025-12-16",{"date":101,"type":21},"2030-11",{"name":48,"class":49},8,{"id":105,"slug":106,"hasResults":11,"nctId":107,"briefTitle":108,"officialTitle":109,"acronym":110,"eligibilityCriteria":111,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":112,"targetDuration":4,"studyType":22,"phases":114,"briefSummary":115,"conditions":116,"keywords":119,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":124,"lastUpdatePostDateStruct":125,"startDateStruct":127,"completionDateStruct":129,"leadSponsor":131,"locationsCount":132},"100612945","phase-2-phase-ii-study-evaluating-ivosidenib-maintenance-after-soc-adjuvant-chemotherapy-in-curative-midh1-cholangiocarcinoma-100612945","NCT07260175","Phase II Study Evaluating Ivosidenib Maintenance After SOC Adjuvant Chemotherapy in Curative mIDH1 Cholangiocarcinoma","adIVO - A Phase II Trial of Ivosidenib Maintenance After SOC Adjuvant Chemotherapy in Curative mIDH1 Cholangiocarcinoma","adIVO","Inclusion Criteria:\n\n1. Patient\\* provides signed informed consent.\n2. Patient is ≥ 18 years at the time of given informed consent.\n3. Patient has histologically documented curatively resected intrahepatic cholangiocarcinoma, without metastatic spread, in the adjuvant situation (R0-resected)\n4. Patient has proven IDH1 mutation (IDH1-variant status evaluated locally by certified test on formalin-fixed paraffin-embedded tumor tissue specimen. If local testing for screening is not possible per local standard, tumor tissue samples will be subject to pre-screening via central IDH1 dPCR)\n5. Patient finished adjuvant systemic SOC chemotherapy (with regimens allowed per the protocol) directly prior to trial inclusion.\n6. Radiologic imaging available that shows that patient is tumor free at the timepoint of enrollment (not older than 6 weeks from the day of inclusion).\n7. Patient has ECOG Performance status ≤ 1\n8. Hematological, hepatic and renal function parameters adequate to allow targeted therapy with ivosidenib at investigator´s discretion and IB.\n9. Patient has adequate coagulability to allow targeted therapy with ivosidenib at investigator´s discretion and IB. Patients receiving warfarin \u002F Phenprocoumon must be switched to low molecular weight heparin and before starting trial-specific.\n10. Patient must be willingly to provide liquid biopsy samples, archival tumor tissue samples (if available), and in the event of disease recurrence, re-biopsy samples (if re-biopsy is considered safe for the patient) for the translational research program.\n11. Female patients of childbearing potential or male patients with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year during the treatment period and for at least 6 months after the last dose of trial treatment. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy. Female patients of child-bearing potential must have a negative pregnancy test within the last 7 days prior to the start of trial therapy.\n12. Patient is willing and able to comply with the protocol (including contraceptive measures) for the duration of the trial including undergoing treatment and scheduled visits and examinations including follow up.\n\nExclusion Criteria:\n\n1. Patient has a metastatic or R+ resected biliary tract cancer.\n2. Patient received previous therapy with an IDH1 inhibitor.\n3. Patient has known presence of tumors other than intrahepatic cholangiocarcinoma or a secondary tumor other than squamous or basal cell carcinomas of the skin or in situ carcinomas of the cervix which have been effectively treated. The sponsor decides to include patients who have received curative treatment and have been disease-free for at least 5 years.\n4. Simultaneous, ongoing systemic immunotherapy, chemotherapy, or hormone therapy not described in the trial protocol.\n5. Patient receives simultaneous treatment with a different anti-cancer therapy other than that provided for in the trial (excluding palliative radiotherapy only for symptom control).\n6. Patient has a stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.\n7. Patient has known allergic \u002F hypersensitive reactions to at least one of the treatment components.\n8. Patient has other serious illnesses or medical ailments within the last 12 months prior to the start of the trial.\n9. Patient has a known presence of an active, uncontrollable infection.\n10. Patient has QTc \\> 480ms or other factors that, in the discretion of the investigator increase significantly the risk of QT prolongation or arrhythmic events (e.g. heart failure, hypokalemia, family history of long QT syndrome). NOTE: Medications that prolong the QT interval should be avoided, unless they can be transferred to other medication within ≥ 5 half-lives to dosing or unless the medications can be properly monitored during the study. (If equivalent medication is not available, QTc should be closely monitored).\n11. Patient has active disseminated intravascular coagulation.\n12. Patient has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n13. Patient has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial drug.\n14. Patient has any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect. NOTE: strong CYP3A4 inducers or sensitive CYP3A4 substrates with narrow therapeutic window should be avoided, unless they can be transferred to alternative medication within at least 5-half lives prior to dosing.\n15. Female patient is pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment.\n16. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.",{"count":113,"type":21},40,[24],"This study trial is a prospective, multicentre, exploratory, single-arm, open-label phase II study to evaluat ivosidenib maintenance after SOC adjuvant chemotherapy in curative mIDH1 cholangiocarcinoma",[117,118],"Cholangiocarcinoma","IDH Mutation",[120,121,122,123],"mIDH1 cholangiocarcinoma","ivosidenib maintenance","cholangiocarcinoma","R0-resection","2026-06-03",{"date":126,"type":42},"2026-06-04",{"date":128,"type":42},"2025-11-18",{"date":130,"type":21},"2031-12",{"name":48,"class":49},12,{"id":134,"slug":135,"hasResults":11,"nctId":136,"briefTitle":137,"officialTitle":137,"acronym":4,"eligibilityCriteria":138,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":139,"enrollmentInfo":140,"targetDuration":4,"studyType":22,"phases":141,"briefSummary":142,"conditions":143,"keywords":4,"overallStatus":145,"whyStopped":4,"lastUpdateSubmitDate":146,"lastUpdatePostDateStruct":147,"startDateStruct":149,"completionDateStruct":151,"leadSponsor":153,"locationsCount":154},"100634668","phase-2-double-t---improving-outcomes-in-high-risk-2nd-line-relapsedrefractory-large-b-cell-lymphoma-patients-eligible-for-car-t-cell-therapy-with-a-glofitamab-based-induction-and-consolidation-concept-100634668","NCT07542678","Double-T - Improving Outcomes in High-risk 2nd Line Relapsed\u002FRefractory Large B-Cell Lymphoma Patients Eligible for CAR-T-cell Therapy With a Glofitamab-based Induction and Consolidation Concept","Inclusion Criteria:\n\n1. Patient\\* has given written informed consent.\n2. Patient is 18-80 years of age at time of signing the written informed consent\n3. Patient has histologically confirmed diagnosis of large B-cell lymphoma by local pathologist at time of relapse.\n4. Patient received R-CHOP based first-line therapy containing a CD20-antibody and anthracyclines.\n5. Patient has relapsed\u002Frefractory disease, defined as follows:\n\n   * Relapsed: disease that had recurred following partial or complete response (PR\u002FCR) within 12 months of adequate first-line therapy\n   * Refractory: disease that did not respond to, or that progressed \\\u003C6 months after, completion of first-line therapy\n6. Patient has at least one FDG-PET positive bi-dimensionally measurable (≥1.5 cm) nodal lesion, or one bi dimensionally measurable (\\>1 cm extranodal lesion, as measured on computed tomography (CT) scan\n7. Patient has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 2\n8. Patient has an absolute lymphocyte count \\> 200\u002FµL\n9. Patient is eligible for CAR-T cell therapy as per investigator´s discretion meeting all of the following criteria of adequate organ function:\n\n   1. Adequate kidney function, defined as: Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 60 mL\u002Fmin.\n   2. Adequate hepatic function, defined as: ALAT and ASAT ≤ 5 ULN. Bilirubin\n\n      ≤ 2.0 mg\u002Fdl (except for Meulengracht disease)\n   3. Adequate bone marrow function, defined as: Absolute neutrophil count (ANC) ≥ 1000\u002FµL, Platelets ≥ 50.000\u002FµL and Hemoglobin \\> 8.0 g\u002FdL.\n   4. Adequate cardiac function, defined as: Cardiac ejection fraction ≥ 45%.\n   5. Adequate pulmonary function as per investigators discretion\n10. Patient successfully performed MNC-leucapheresis procedure for a commercially available CAR-T-cell product\n11. Patient is willing and able to provide baseline biopsy material (archival or fresh tumor sample) for central review\n12. Male patients with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods throughout the duration of the trial and at least 18 months after obinutuzumab administration, 12 months after lost dose oxaliplatin, 6 months after lymphodepletion or 2 months after last dose glofitamab, whatever is last\n13. Female participants of childbearing potential must agree to use a highly effective method of contraception (e.g., hormonal contraception, intrauterine device (IUD), or surgical sterilization) throughout the duration of the trial and at least 18 months after obinutuzumab administration, 15 months after lost dose oxaliplatin, 6 months after lymphodepletion or 2 months after last dose glofitamab, whatever is last. \\* There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the trial gender-independently\n\nExclusion Criteria:\n\n1. Patient has HIV infection of any stage as determined by presence of anti-HIV antibodies (confirmatory test) and \u002F or presence of RNA confirmed by PCR during screening\n2. Patient has previous or concurrent malignancies with the following exceptions:\n\n   1. Surgically cured carcinoma in-situ\n   2. Other kinds of cancer without evidence of disease for at least 3 years\n3. Patient has known hypersensitivity to any component of the Glofitamab, Obinutuzumab, Yescarta and\u002For Breyanzi formulation formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein and\u002For any known contraindication (including hypersensitivity) to one of the other trial drugs\n4. Patient has severe active infection requiring iv treatment within 14 days prior first dose of study drugs\n5. Patient has congenital or acquired immunodeficiency including previous organ or allogeneic stem cell transplantation\n6. Patient received prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3\n7. Patient received prior treatment with gemcitabine and oxaliplatin in prior lymphoma treatment line\n8. Patient had a major surgery within 4 weeks prior to first dose of study drugs\n9. Patient has primary or secondary central nervous system (CNS) lymphoma at the time of enrollment or history of CNS lymphoma\n10. Patient has current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease\n11. Patient has significant or extensive cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 3 months, unstable arrhythmias, or unstable angina\n12. Patient has an active autoimmune disease requiring systemic treatment\n13. Patient receives ongoing corticosteroid use \\>20 mg\u002Fday of prednisone or equivalent. Patients on stable low-dose corticosteroids (≤20 mg\u002Fday of prednisone or equivalent for at least 7-14 days prior to first IMP administration) or on short courses of higher-dose corticosteroids that are completed before first IMP administration are eligible.\n14. Female patients who are pregnant or breast feeding or planning to become pregnant within up to 18 months after start of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 3 days prior to initiation of trial treatment.\n15. Patient has a relationship of dependence or employer-employee relationship to the sponsor or the investigator\n16. Patient lacks accountability and inability to appreciate the nature, meaning and consequences of the trial\n17. Patient is non-compliant, for reasons including, but not limited to the following:\n\n    * Increased alcohol consumption, drug dependency or substance abuse that would interfere with cooperation with requirements of the trial\n    * Refusal of blood products during treatment\n    * Any similar circumstances that appear to make protocol treatment or follow-up impossible","80 Years",{"count":50,"type":21},[24],"The Double-T trial is a prospective, randomized, single-arm, open-label, multicenter phase II trial investigating a double T-cell therapy strategy, which includes glofitamab with gemcitabine\u002Foxaliplatin (Glofi-Gem\u002FOx) prior to and glofitamab monotherapy consolidation after standard of care Chimeric Antigen Receptor (CAR)-T cell therapy in high-risk 2nd line relapsed\u002Frefractory Large B-Cell Lymphoma (r\u002Fr LBCL) patients.\n\nData on safety, efficacy, and quality of life (QoL) will be collected and analyzed.",[144],"Relapsed \u002FRefractory DLBCL","NOT_YET_RECRUITING","2026-04-17",{"date":148,"type":42},"2026-04-21",{"date":150,"type":21},"2026-04",{"date":152,"type":21},"2030-04",{"name":48,"class":49},5,{"id":156,"slug":157,"hasResults":11,"nctId":158,"briefTitle":159,"officialTitle":160,"acronym":161,"eligibilityCriteria":162,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":163,"targetDuration":4,"studyType":165,"phases":4,"briefSummary":166,"conditions":167,"keywords":171,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":178,"lastUpdatePostDateStruct":179,"startDateStruct":181,"completionDateStruct":183,"leadSponsor":185,"locationsCount":186},"100632210","real-world-data-on-the-treatment-of-lung-cancer-patients-with-the-immune-checkpoint-inhibitor-tislelizumab-100632210","NCT07510724","Real-World Data on the Treatment of Lung Cancer Patients With the Immune-Checkpoint Inhibitor Tislelizumab","Real-World Data on the Treatment of Lung Cancer Patients With the Immune-Checkpoint Inhibitor Tislelizumab - the ReWoLuTe Study","IKF-ReWoLuTe","Inclusion criteria:\n\n* Patient has a histologically confirmed resectable Non-small cell lung cancer in stage II-IIIA with high risk of recurrence according to the 8th edition of the following AJCC staging criteria and is eligible for an R0 resection with curative intent and treatment with Tislelizumab in neoadjuvant and adjuvant setting:\n\n  1. Tumor size \\>4cm; or tumors of any size with either N1 or N2 status\n  2. Tumors invading thoracic structures (directly into the visceral pleura, parietal pleura, chest wall, main bronchus, phrenic nerve, mediastinal pleura, parietal pericardium)\n  3. Tumors \\>4cm that cause obstructive atelectasis extending to the hilum and involving parts of the lung, the entire lung or a main bronchus, regardless of the distance to the carina, or that invade the visceral pleura (PL1 or PL2)\n  4. Tumors with one or more separate nodules in the same lobe as the primary lung carcinoma.\n\n     OR\n\n     Patient has a histologically confirmed locally advanced or metastatic lung carcinoma of one of the following subtypes and is eligible for treatment with Tislelizumab in an approved indication:\n  5. NSCLC, squamous type, and the patient is not a candidate for surgical resection or platinum-based chemoradiation and did not receive prior treatment in palliative setting,\n  6. NSCLC, non-squamous type with PD-L1 expression on ≥50% of tumor cells and without EGFR- or ALK-positive mutations, and patient is not candidate for surgical resection or platinum-based chemoradiation and did not receive prior treatment in palliative setting,\n  7. NSCLC, squamous or non-squamous type, and the patient already received prior platinum-based therapy and, if with EGFR- or ALK-positive mutations, also has received targeted therapies,\n  8. SCLC, extensive-stage, and the patient has not received prior treatment in palliative setting.\n* A decision for treatment with an authorized Tislelizumab-based regimen has been made by the treating physician before enrolling into ReWoLuTe study.\n\nNOTE:\n\nPatients who have already received 1-2 cycles of therapy are still eligible for enrollment into the NIS. Patients who intended to be treated in the curative setting and had to switch before the start of an adjuvant treatment to the palliative setting or BSC (e.g. due to progress or other reasons), will not be excluded from study.\n\nExclusion criteria:\n\n* The patient has not provided signed informed consent.\n* The patient is under 18 years of age at the time of providing signed informed consent.\n* The patient is unable to fully comprehend the implications of study participation.",{"count":164,"type":21},240,"OBSERVATIONAL","The ReWoLuTe study (IKF091) is a prospective, multi-center, observational cohort study conducted in Germany and Austria to collect real-world data on the use of Tislelizumab-based therapies in patients with lung cancer. The study aims to evaluate the overall survival, treatment patterns, safety, and health-related quality of life of patients receiving Tislelizumab in everyday clinical practice.",[168,169,170],"Small Cell Lung Cancer (SCLC)","Non-Small Cell Lung Cancer (NSCLC)","Lung Cancer (Diagnosis)",[172,173,174,175,176,177],"Lung Cancer","Tislelizumab-based therapy","real-world data on tislelizumab treated patients","resectable NSCLC (perioperative setting)","locally advanced or metastatic NSCLC (1st\u002F2nd line)","extensive-stage SCLC (1st line)","2026-03-30",{"date":180,"type":42},"2026-04-03",{"date":182,"type":42},"2025-12-23",{"date":184,"type":21},"2033-01-23",{"name":48,"class":49},2,{"id":188,"slug":189,"hasResults":11,"nctId":190,"briefTitle":191,"officialTitle":192,"acronym":4,"eligibilityCriteria":193,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":194,"targetDuration":4,"studyType":22,"phases":196,"briefSummary":197,"conditions":198,"keywords":200,"overallStatus":145,"whyStopped":4,"lastUpdateSubmitDate":178,"lastUpdatePostDateStruct":206,"startDateStruct":208,"completionDateStruct":210,"leadSponsor":212,"locationsCount":213},"100631998","phase-2-tnt-with-flotdurvalumab-plus-post-op-durvalumab-for-resectable-gastroesophageal-adenocarcinoma-100631998","NCT07507968","TNT With FLOT\u002FDurvalumab Plus Post-OP Durvalumab for Resectable Gastroesophageal Adenocarcinoma","Total Neoadjuvant Treatment With Preoperative FLOT\u002FDurvalumab Plus Postoperative Durvalumab for Resectable Gastroesophageal Adenocarcinoma","Inclusion Criteria:\n\n* Patient\\* has given written informed consent\n* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up\n* Patient is ≥ 18 years of age at time of signing the written informed consent\n* Patient has histologically proven locally advanced (cT2-4, any cN, M0 OR any cT, cN+, M0 stage) gastric, esophagogastric junction (type 1-3) or lower esophageal adenocarcinoma that is considered medically and technically resectable\n* Patient has a known PD-L1 status according to standardized TAP scoring (by local testing), any PD-L1 status is eligible\n* Patient has a ECOG performance status 0 or 1\n* Patient must have a life expectancy of at least 12 weeks\n* Patient has adequate blood count, liver-enzymes, and renal function:\n\n  1. ANC ≥ 1.0x109 cells\u002FL without the use of hematopoietic growth factors\n  2. Platelet count ≥ 75 x 109\u002FL (\\>75,000 per mm3)\\*\\*\n  3. Hemoglobin ≥ 9 g\u002FdL\\*\\*\n  4. Serum total bilirubin ≤ 1.5x institutional upper normal limit (ULN)\n  5. AST (SGOT)\u002FALT (SGPT) ≤ 2.5 x institutional ULN\n  6. Patients not receiving therapeutic anticoagulation must have an INR ≤ 1.5 ULN and aPTT ≤ 1.5 ULN. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of inclusion.\n  7. Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate \\> 40 mL \u002Fmin.\n* Patient has a body weight \\> 30 kg\n* Female patients defined as women of childbearing potential (WOCBP) must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year during the treatment period and for 3 months after last dose of durvalumab or 6 months after last dose of chemotherapy, whatever is later\n* Male patients with WOCBP partners must agree to remain abstinent (refrain from heterosexual intercourse) or use barrier contraceptive during the treatment period as well as up to 3 months after last dose of durvalumab or up to 6 months after last dose of chemotherapy, whatever is later. Male patients must refrain from donating sperm during this same period\n\nExclusion Criteria:\n\n* Patient received previous (radio)chemotherapy or checkpoint inhibition for the same condition or within the past five years for any other cancerous condition\n* Patient received prior partial or complete esophagogastric tumor resection\n* Patient has known hypersensitivity to any component of the durvalumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein and\u002For any known contraindication (including hypersensitivity) to one of the study drugs\n* Patient has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease that required steroids or has current pneumonitis\u002Finterstitial lung disease\n* Patient has 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 enrolment, severe asthma, severe COPD, restrictive lung disease, relevant pleural effusion etc.)\n* Patient received a prior complete pneumonectomy\n* Patient has inadequate cardiac function (LVEF value \\\u003C 50 %) as determined by echocardiography\n* Patient has a known complete absence of dihydropyrimidine dehydrogenase (DPD) activity\n* Patient received treatment with brivudine, sorivudine or their chemically related analogues within 28 days prior to stud enrollment\n* Patients has pernicious anemia or other megaloblastic anemia due to vitamin B12 deficiency\n* Patient has a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation during screening to rule out MI\n* Patient has a corrected QT interval (QTc) prolongation to \\> 470 ms (females) or \\>450 ms (males) based on average of the screening triplicate ECG\n* Patient has a history of malignancy other than EGA except for:\n\n  1. Malignancy treated with curative intent and cured with no known active disease ≥ 3 years before the first dose of study treatment and of low potential risk for recurrence.\n  2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.\n  3. Adequately treated carcinoma in situ without evidence of disease\n* Patient has an uncontrolled infection requiring IV antibiotics, antivirals or antifungals within 14 days prior to enrolment\n* Patient has active HBV infection, which is characterized by positive HBV surface antigen (HBsAg) and\u002For positive HBc antibodies (anti-HBcAb) with detectable HBV DNA (≥ 10 IU\u002FmL or above the limit of detection per local laboratory standard), unless the participant is treated with antiviral therapy, as per institutional practice. The HBV antiviral therapy must be initiated prior to randomization, and participants must remain on antiviral therapy for the study duration and for 6 months after the last dose of response (e.g., reduction HBV DNA levels) prior to starting intervention.\n\nNote: Patients who test positive for HBsAg or anti-HBc with undetectable HBV DNA (\\\u003C 10 IU\u002FmL or under the limit of detection per local laboratory standard) do not require antiviral therapy prior to enrollment. These patients are eligible and will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥ 10 IU\u002FmL or above the limit of detection per local laboratory standard). The HBV DNA detectable patients must initiate and remain on antiviral therapy for the trial duration and for 6 months after the last dose of durvalumab\n\n* Patient has active HCV infection (as characterized by the presence of detectable HCV RNA and anti-HCV antibody \\[anti-HCV\\]) unless the patient is managed per local institutional practice for the trial and for 6 months after the last dose of durvalumab\n* Patient has any co-infection with HBV and HDV (HDV-positive infection is indicated by the presence of anti-HDV antibodies)\n* Patient has active tuberculosis infection (clinical evaluation that may include clinical history, physical examination, and radiographic findings, or tuberculosis testing in line with local practice)\n* Patient has known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled:\n\n  1. Undetectable viral RNA\n  2. CD4+ count ≥ 350 cells\u002Fmm3\n  3. No history of acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen).\n\nIf an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended. Patient must be tested for HIV if acceptable by local regulations or an institutional IRB\u002FIEC.\n\n* Patient has active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. The following are exceptions to this criterion:\n\n  1. Patients with vitiligo or alopecia\n  2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement\n  3. Any chronic skin condition that does not require systemic therapy\n  4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician\n  5. Patients with celiac disease controlled by diet alone\n* Patient currently or priorly used immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:\n\n  1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)\n  2. Systemic corticosteroids at physiologic doses not to exceed 10 mg\u002Fday of prednisone or its equivalent\n  3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)\n* Patient received live, attenuated vaccine within 30 days prior initiation of study drug\n* Patient has any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect\n* Patient participated in another interventional clinical study within 28 days prior to study enrollment or participation in a clinical study at the same time as this study, unless it is an observational\u002F non-interventional study or during the follow-up period of an interventional study\n* Patient has taken an investigational drug within 28 days prior to initiation of study drug\n* Female patients, who are pregnant or breast feeding or planning to become pregnant within 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment",{"count":195,"type":21},101,[24],"This trial is designed to evaluate a total neoadjuvant approach using D-FLOT as the new standard backbone in patients with resectable esophagogastric adenocarcinoma. It addresses major limitations of current treatment paradigms, builds directly on the strong clinical signal from the MATTERHORN trial, and offers a rational, biologically sound framework for future therapy intensification and innovation.\n\nBy moving systemic therapy entirely into the preoperative phase, we aim to:\n\n* Improve patient outcomes through better adherence and deeper response\n* Minimize postoperative therapy-related dropout\n* Create a platform for rational post-surgical drug testing and individualized treatment escalation The trial will provide pivotal evidence to guide the next generation of curative-intent treatment strategies for EGA.",[199],"Esophagogastric Adenocarcinoma",[201,202,203,204,205],"neoadjuvant","gastric","esophageal","Durvalumab","FLOT chemotherapy",{"date":207,"type":42},"2026-04-02",{"date":209,"type":21},"2026-07-01",{"date":211,"type":21},"2030-02-01",{"name":48,"class":49},29,{"id":215,"slug":216,"hasResults":11,"nctId":217,"briefTitle":218,"officialTitle":219,"acronym":220,"eligibilityCriteria":221,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":222,"targetDuration":4,"studyType":22,"phases":224,"briefSummary":225,"conditions":226,"keywords":229,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":235,"lastUpdatePostDateStruct":236,"startDateStruct":238,"completionDateStruct":240,"leadSponsor":242,"locationsCount":243},"100591507","phase-2-evaluation-of-efficacy-and-safety-of-cemiplimab-as-first-line-treatment-for-advanced-basal-cell-carcinoma-bcc-patients-100591507","NCT06981325","Evaluation of Efficacy and Safety of Cemiplimab as First Line Treatment for Advanced Basal Cell Carcinoma (BCC) Patients","Evaluation of Efficacy and Safety of Cemiplimab as First Line Treatment for Advanced Basal Cell Carcinoma (CEMI-first) - An Open Label, Single Arm, Prospective Phase II Trial of the DeCOG Network","CEMI-first","Inclusion Criteria:\n\n1. Signed informed consent form available\n2. Patient\\* 18 years or older at time of signing informed consent form\n3. Centrally confirmed histological diagnosis of BCC\n\n   NOTE: Tumor tissue to be sent to Central Pathology during screening procedure:\n   * Formalin-fixed, parrafin-embedded (FFPE) tumor specimen in a paraffin block (preferred) OR\n   * approximately 10 sections (5µm thickness) on uncoated slides and 10 sections (5µm thickness) on Superfrost Ultra slides containing unstained, freshly cut, serial sections to be submitted along with associated pathology report (please refer to section 11.1.1 for details)\n4. Locally advanced stage without distant metastases, not amenable for surgery or radiotherapy or surgery\u002Fradiotherapy contraindicated or refused by patient (as evidenced in source data)\n5. Expected survival of at least 6 months\n6. ECOG performance status 0 or 1\n7. Adequate laboratory parameters particularly for the blood count, renal and liver function parameters.\n\n   1. Absolute number of neutrophils ≥ 1.5 x 109\u002FL\n   2. Platelets ≥ 75 x 109\u002FL\n   3. Hemoglobin ≥ 9 g\u002FdL\n   4. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), (patients with Gilbert´s Disease and total bilirubin up to 3x ULN may be eligible after approval from trial's medical expert)\n   5. AST (SGOT) and ALT (SGPT) ≤ 3x ULN\n   6. AP ≤ 2.5x ULN\n   7. Serum creatinine ≤ 2x ULN or creatinine clearance ≥ 40 mL\u002Fmin\n8. Absence of other severe comorbidities\n9. Resolution of any acute, clinically significant treatment-related adverse events from prior therapy\u002Fprocedure to Grade ≤ 1 prior to study entry, with the exception of alopecia.\n10. Negative serum pregnancy test done less than or equal to 7 days prior to enrollment, for females of childbearing potential only.\n11. Sexually active women of childbearing potential (WOCBP) and men with WOCBP partners must be prepared to use suitable contraceptive method with a failure rate of \\\u003C 1% per year during the treatment period and for at least 6 months after the last dose of Cemiplimab\n\n    * There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently\n\nExclusion Criteria:\n\n1. Pretreatment with systemic immunotherapy (such as PD-1\u002FPD-L1 or CTL4) or targeted therapy (such as hedgehog inhibitor) NOTE: Prior treatment with imiquimod or other topical or intralesional immune modulators will not be exclusionary\n2. Any other non-radiation anti-cancer therapy (e.g. imiquimod, photodynamic therapy; neither investigational nor standard of care) within 30 days (from date of last administration) of initial Cemiplimab administration or if planned during the study duration\n3. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required systemic immunosuppressive therapy, excluding: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism requiring only hormone replacement, or psoriasis that does not require systemic treatment\n4. Other neoplasia, in particular hematologic diseases that might impair immune response, such as chronic lymphocytic leukemia, myelodysplastic or myeloproliferative disease and patients with Gorlin-Goltz syndrom\n5. Immunosuppressive corticosteroid doses (\\> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of Cemiplimab NOTE: Patients who require brief courses of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are eligible for participation. Furthermore, patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or replacement in case of adrenal or hypophysis insufficiency are eligible for participation.\n6. Known allergic\u002Fhypersensitive reaction to the study drug and any of its excipients or history of documented allergic\u002Fhypersensitive reactions to antibody treatments\n7. Active infection requiring systemic therapy, including uncontrolled HIV, HBV and HCV infection or diagnosis of immunodeficiency.\n\n   NOTE: Patients are eligible if:\n   * Patients have controlled HIV infection with CD4 counts is \\> 350 cells\u002FµL and viral load is undectable \\[HIV RNA PCR\\]\n   * Patients positive for HBV surface antigen have controlled HBV infection receiving anti-viral therapy and with undectable serum viral load \\[HBV DNA PCR\\]. Patients must remain on anti-viral therapy for at least 6 months after last dose of Cemiplimab\n   * Patients positive for HCV antibody have controlled HCV infection with undectable viral load \\[HCV RNA PCR\\]\n8. History of pneumonitis within the last 3 years\n9. Patients with history of solid organ transplant (patients with prior corneal transplants may be allowed to enroll after discussion with and approval from the Lead Investigator)\n10. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n11. Receipt of live vaccines (including attenuated) within 30 days of first administration of Cemiplimab\n12. Pregnancy or lactation period.\n13. Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.\n14. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results\n15. Legal incapacity or limited legal capacity.\n16. On-treatment participation in another clinical trial in the period 30 days prior to start of the study treatment and during the study",{"count":223,"type":21},34,[24],"The study is an open-label, singel arm, prospective, multicenter phase II trial evaluating the efficacy and safety of Cemiplimab when applied as first-line therapy in patients with locally advanced basal cell carcinoma (BCC), which were not pretreated with hedgehog inhibitors (HHI).",[227,228],"Basal Cell Carcinoma (BCC)","First Line Treatment",[230,231,232,233,234,72],"BCC","Skin Cancer","Basal Cell Carcinoma","anti-PD-1 monoclonal antibody","HHI naïve","2026-03-10",{"date":237,"type":42},"2026-03-11",{"date":239,"type":42},"2025-08-07",{"date":241,"type":21},"2029-07",{"name":48,"class":49},7,{"id":245,"slug":246,"hasResults":11,"nctId":247,"briefTitle":248,"officialTitle":249,"acronym":250,"eligibilityCriteria":251,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":252,"targetDuration":4,"studyType":165,"phases":4,"briefSummary":254,"conditions":255,"keywords":257,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":268,"lastUpdatePostDateStruct":269,"startDateStruct":271,"completionDateStruct":273,"leadSponsor":275,"locationsCount":276},"100621077","nis-on-the-benefits-of-tips-in-patients-with-hcc-receiving-atezobev-in-1st-line-therapy-100621077","NCT07365930","NIS on the Benefits of TIPS in Patients With HCC Receiving Atezo+Bev in 1st-Line Therapy","Non-Interventional Study on the Benefits of Transjugular Intrahepatic Portosystemic Shunting in Patients With Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab in First-Line Therapy","NISTIPS","Inclusion Criteria:\n\n1. The patient has a histologically confirmed, locally advanced or metastatic and\u002For unresectable HCC with:\n\n   1. the presence of liver cirrhosis (cirrhosis confirmed by histology or liver stiffness or with unequivocal signs in ultrasound, endoscopy, and\u002For blood tests),\n   2. a disease that is not amenable to curative surgical and\u002For locoregional therapies, or a progressive disease after surgical and \u002For locoregional therapies,\n2. A decision for treatment with atezolizumab + bevacizumab according to the market authorization with or without TIPS has been made before enrolling into the study by the treating physician.\n\nNOTE: Patients who have already received 1-2 cycles of atezo+bev therapy are eligible for enrollment into the NISTIPS TRITICC-4 study, when the prescription of the medicine or other therapeutic strategies are clearly separated from the decision to include the patient in the study.\n\nExclusion Criteria:\n\n1. The patient has not provided signed informed consent.\n2. The patient is under 18 years of age at the time of giving signed informed consent.\n3. The patient is unable to understand all implications of study participation.",{"count":253,"type":21},350,"The NISTIPS TRITICC-4 study is a prospective, multicentre, non-interventional cohort study to analyze the effectiveness of transjugular intrahepatic portosystemic shunting (TIPS) in patients with Hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab as first-line treatment. It will further characterize the effectiveness of atezolizumab and bevacizumab therapy, investigate post-market safety and evaluate health-related quality in HCC patient cohorts with or without TIPS in a real-world setting.",[256],"Hepatocellular Carcinoma (HCC)",[258,259,260,261,262,263,264,265,266,267],"HCC","TIPS","Tecentriq","Avastin","transjugular intrahepatic portosystemic shunting","Hepatocellular carcinoma","observational study","non-interventional study","Atezolizumab","Bevacizumab","2026-02-03",{"date":270,"type":42},"2026-02-05",{"date":272,"type":42},"2025-12-17",{"date":274,"type":21},"2031-12-17",{"name":48,"class":49},1,{"id":278,"slug":279,"hasResults":11,"nctId":280,"briefTitle":281,"officialTitle":281,"acronym":282,"eligibilityCriteria":283,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":284,"targetDuration":286,"studyType":165,"phases":4,"briefSummary":287,"conditions":288,"keywords":293,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":268,"lastUpdatePostDateStruct":296,"startDateStruct":297,"completionDateStruct":299,"leadSponsor":301,"locationsCount":302},"100371937","gisar-german-interdisciplinary-sarcoma-registry-100371937","NCT04122872","GISAR German Interdisciplinary Sarcoma Registry","GISAR","Inclusion Criteria:\n\n* Histological verified bone or soft tissue sarcomas including bone and soft tissue tumors with borderline histological results or with unclear histological dignity like giant cell tumors of the bone (GCTB), desmoid tumors, atypical lipomatous tumors etc. - independent of therapy form and therapy line - or Histological verified sarcomatoid carcinomas\u002F carcinosarcomas: tumors with histological, cytological, or molecular properties of both epithelial tumors (\"carcinoma\") and mesenchymal tumors (\"sarcoma\") - independent of therapy form and therapy line.\n* Signed informed consent form or equivalent (s. chapter 10)\n* Age ≥18 years\n\nExclusion Criteria:\n\n* none",{"count":285,"type":21},9000,"10 Years","GISAR has an open and modular setup. It is sought to include as many German sarcoma and CS patients (i.e. sarcoma and CS patients treated in Germany) in the registry as possible. A basic data set should be collected on every included patient). In order to adress specific scientific questions, additionally detailed data can be collected in defined patient groups (e.g. effectiveness \u002F adverse effects of systemic therapies in defined situations) within the context of sub-project add-on modules. This data collection can be prospective or retrospective depending on the sub-project",[289,290,291,292],"Sarcoma","Sarcoma,Soft Tissue","Sarcoma of Bone","Carcinosarcoma",[289,294,291,295],"Soft Tissue Sarcoma","Registry",{"date":270,"type":42},{"date":298,"type":42},"2018-11-29",{"date":300,"type":21},"2038-01",{"name":48,"class":49},21,{"id":304,"slug":305,"hasResults":11,"nctId":306,"briefTitle":307,"officialTitle":308,"acronym":309,"eligibilityCriteria":310,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":311,"targetDuration":4,"studyType":22,"phases":313,"briefSummary":314,"conditions":315,"keywords":317,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":182,"lastUpdatePostDateStruct":322,"startDateStruct":324,"completionDateStruct":325,"leadSponsor":327,"locationsCount":328},"100571586","phase-2-futibatinib-in-combination-with-chemoimmunotherapy-in-colorectal-cancer-and-other-solid-tumor-entities-100571586","NCT06722183","Futibatinib in Combination With (Chemo)Immunotherapy in Colorectal Cancer and Other Solid Tumor Entities","FUTURE Platform Trial - A Phase II Platform Trial of Futibatinib in Combination With (Chemo)Immunotherapy in Colorectal Cancer and Other Solid Tumor Entities","FUTURE","Inclusion Criteria:\n\n1. Patient\\* provides signed informed consent.\n2. Patient is ≥ 18 years at the time of given informed consent.\n3. Patient has a histologically proven solid tumor:\n\n   • Specific for FUTURE-001: Histological or cytological confirmation of colorectal adenocarcinoma that is unresectable and\u002For metastatic with known RAS-, BRAF and MSI- status.\n4. Specific for FUTURE-001: Patient must agree to participation in the accompanying translational research program.\n5. Specific for FUTURE-001: Patient did not receive previous therapy in palliative setting (1st line situation).\n6. Patient has ECOG Performance status ≤ 1.\n7. Patient has adequate blood count, liver-enzymes, and renal function:\n\n   1. ANC \\> 1,500 cells\u002FμL without the use of hematopoietic growth factors\n   2. Platelet count ≥ 100 x 109\u002FL (\\>100,000 per mm3)\n   3. Hemoglobin ≥ 9 g\u002FdL, transfusion allowed\n   4. Serum total bilirubin ≤ 1.5x institutional upper normal limit (ULN) (or \\\u003C 2 x ULN in case of liver involvement or Gilbert's disease)\n   5. AST (SGOT)\u002FALT (SGPT) ≤ 2.5 x institutional ULN without existing liver metastases, or ≤ 5 x UNL in the presence of liver metastases; AP ≤ 5 x ULN\n   6. Patients not receiving therapeutic anticoagulation must have an INR ≤ 1.5 ULN and aPTT ≤ 1.5 ULN. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of inclusion\n   7. Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate ≥ 50 mL \u002Fmin\n8. Patient has serum calcium and phosphate levels within normal range.\n9. Female patients of childbearing potential or male patients with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year during the treatment period and in FUTURE-001 for at least 1 week after last dose of futibatinib, 6 months after the last dose of chemotherapy or 4 months after last dose of tislelizumab, whatever is later. Male patients should refrain from sperm donation\u002F cryopreservation throughout this period and male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy. Female patients of child-bearing potential must have a negative pregnancy test within the last 7 days prior to the start of trial therapy.\n10. Patient is willing and able to comply with the protocol (including contraceptive measures) for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n\n    * There is no data that indicates a specific gender distribution. Therefore, patients are included regardless of their gender.\n\nExclusion Criteria:\n\n1. Specific for FUTURE-001: Patient has curative colorectal cancer.\n2. Patient received previous FGFR-addressed therapy with an FGFR inhibitor.\n3. Patient has known presence of tumors other than the entity investigated in the respective cohort (FUTURE-001: colorectal cancer) or a secondary tumor other than squamous or basal cell carcinomas of the skin or in situ carcinomas of the cervix which have been effectively treated. The sponsor decides to include patients who have received curative treatment and have been disease-free for at least 5 years\n4. Patient has known untreated or symptomatic CNS or leptomeningeal metastases.\n5. Patient has history and\u002For current evidence of any of the following disorders:\n\n   1. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the investigator\n   2. Ectopic mineralization\u002Fcalcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the investigator\n6. Patient receives simultaneous, ongoing systemic immunotherapy, chemotherapy, or hormone anti-cancer therapy or any other anti-cancer treatment not described in the trial protocol (excluding palliative radiotherapy only for symptom control).\n7. Patient has a stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.\n8. Patient has known allergic \u002F hypersensitive reactions to at least one of the treatment components.\n9. Patient shows a ≥ grade 2 neuropathy\n10. Patient takes St. Johns Wort within 6 weeks prior to initiation of study treatment\n11. Patient has evidence of or any ongoing ophthalmological disorders. including but not limited to, central serous retinopathy, macular\u002Fretinal degeneration, diabetic retinopathy, and previous retinal detachment\n12. Patient has other serious illnesses or medical ailments within the last 12 months prior to the start of the study.\n13. Patient has a known presence of an active, uncontrollable infection.\n14. Patient has active disseminated intravascular coagulation.\n15. Patient has any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect.\n16. Patient participated in another interventional clinical study within 28 days prior to study enrollment or participation in a clinical study at the same time as this study, unless it is an observational\u002F non-interventional study or during the follow-up period of an interventional study.\n17. Patient received treatment with any of the following within the specified time frame prior to the first dose of study treatment:\n\n    1. Major surgery within 4 weeks (surgical incision should be fully healed)\n    2. Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks\n    3. Any investigational drug within 4 weeks\n18. Female patients, who are pregnant or breast feeding or planning to become pregnant within 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment\n19. Specific for FUTURE-001: Patient received prior treatment with PD-(L)1 or CTLA-4 targeted treatment\n20. Specific for FUTURE-001: Patient has any active autoimmune disease or has a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis , hyperthyroidism; patients with vitiligo; asthma that has been completely remitted in childhood and does not require any intervention in adulthood can be included; patients with asthma requiring medical intervention with bronchodilators cannot be included)\n21. Specific for FUTURE-001: Patient has immune deficiency or receives systemic steroid hormone therapy (\\> 10mg\u002Fday prednisone or other equivalents), or other form of immunosuppressive therapy within 2 weeks prior treatment initiation\n22. Specific for FUTURE-001: Patient has history of uncontrolled infection with human deficiency virus (HIV) or chronic infection with hepatitis B or C virus (HBV, HCV)\n23. Specific for FUTURE-001: Patient has received a solid organ transplantation\n24. Specific for FUTURE-001: Patient has history of interstitial lung disease",{"count":312,"type":21},33,[24],"The FUTURE trial is a prospective, multicentre, exploratory, open-label phase II platform trial. Its goal is to evaluate the efficacy, feasibility and safety of futibatinib combined with immunotherapeutic, targeted or chemotherapeutic agents in colorectal and other solid tumors and to additionally identify biomarkers that correlate with clinical outcome.",[316],"Colorectal Cancer",[318,319,320,321],"platform trial","colorectal cancer","futibatinib","phase II",{"date":323,"type":42},"2025-12-24",{"date":99,"type":21},{"date":326,"type":21},"2028-03",{"name":48,"class":49},10,{"id":330,"slug":331,"hasResults":11,"nctId":332,"briefTitle":333,"officialTitle":334,"acronym":335,"eligibilityCriteria":336,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":337,"targetDuration":4,"studyType":22,"phases":339,"briefSummary":341,"conditions":342,"keywords":348,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":352,"lastUpdatePostDateStruct":353,"startDateStruct":355,"completionDateStruct":356,"leadSponsor":358,"locationsCount":359},"100597500","phase-1-a-phase-ib-trial-evaluating-the-safety-and-activity-of-neoadjuvant-combination-of-tislelizumab-plus-flot-for-resectable-esophagogastric-adenocarcinoma-100597500","NCT07059299","A Phase Ib Trial Evaluating the Safety and Activity of Neoadjuvant Combination of Tislelizumab Plus FLOT for Resectable Esophagogastric Adenocarcinoma","NeoTISLEGA - A Phase Ib Trial Evaluating the Safety and Activity of Neoadjuvant Combination of Tislelizumab Plus FLOT for Resectable Esophagogastric Adenocarcinoma","NeoTISLEGA","Inclusion Criteria:\n\n1. Patient\\* has given written informed consent.\n2. Patient is ≥ 18 years of age at time of signing the written informed consent.\n3. Patient has histologically proven locally advanced (cT2-4 , any cN , M0 OR any cT, cN+, M0 stage) gastric, esophageal or esophagogastric junction adenocarcinoma that:\n\n   1. Is considered technically resectable.\n   2. Does not involve distant site of the peritoneal cavity.\n\n      * confirmed by diagnostic laparoscopy for all patients with tumors located in the stomach and those with type 2 and 3 GEJ adenocarcinomas according to ESMO guideline recommendation \\[Lordick et al. 2022\\].\n      * Type 1 GEJ and esophageal adenocarcinomas can be enrolled without diagnostic laparoscopy (which is in line with guidelines and the current routine practice in Germany).\n4. Tumor material is available for local assessment of PD-L1 (CPS) and dMMR\u002FMSI-status at the investigator´s site.\n5. Patient has an ECOG performance status 0 or 1.\n6. Patients has adequate blood count, liver-enzymes, and renal function:\n\n   1. ANC (Absolute neutrophil count) \\> 1,500 cells\u002FμL without the use of hematopoietic growth factors.\n   2. Platelet count ≥ 100 x 10\\^9\u002FL (\\>100,000 per mm3).\n   3. Hemoglobin ≥ 9 g\u002FdL.\n   4. Serum total bilirubin ≤ 1.5x institutional upper normal limit (ULN).\n   5. AST (SGOT)\u002FALT (SGPT) ≤ 2.5 x institutional ULN.\n   6. Patients not receiving therapeutic anticoagulation must have an INR ≤ 1.5 ULN and aPTT ≤ 1.5 ULN. The use of full dose anticoagulants is allowed (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of inclusion.\n   7. Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate ≥ 50 mL \u002Fmin.\n7. Female patients defined as women of childbearing potential (WOCBP) must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C 1% per year during the treatment period and for 4 months after last dose of tislelizumab or 6 months after the last dose of chemotherapy, whatever is later. Male patients with WOCBP partners must agree to remain abstinent (refrain from heterosexual intercourse) or use barrier contraceptives during the above period. Furthermore, male patients must refrain from donating sperm during this same period.\n\n   * There are no data that indicate special gender distribution. Therefore, patients will be enrolled gender-independently in this trial.\n\nExclusion Criteria:\n\n1. Patient received previous (radio)chemotherapy or immunotherapy for the same condition or within the past five years for any other cancerous condition.\n2. Patient received prior partial or complete esophagogastric resection.\n3. Patient has known hypersensitivity to any component of the tislelizumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein and\u002For any known contraindication (including hypersensitivity) to one of the study drugs.\n4. Patient has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease that required steroids or has current pneumonitis\u002Finterstitial lung disease.\n5. Patient has 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 randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.).\n6. Patient has inadequate cardiac function (LVEF value \\\u003C 50 %) as determined by echocardiography.\n7. Patient has a known complete absence of dihydropyrimidine dehydrogenase (DPD) activity.\n8. Patient received treatment with brivudine, sorivudine or their chemically related analogues within 28 days prior to study enrollment.\n9. Patients has pernicious anemia or other megaloblastic anemia due to vitamin B12 deficiency.\n10. Patient has peripheral sensitive neuropathy with functional deficits.\n11. Patient has a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF; New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation during screening to rule out MI.\n12. Patient has a corrected QT interval (QTc) prolongation to \\> 470 ms (females) or \\>450 ms (males) based on average of the screening triplicate12-lead ECG.\n13. Participant has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.\n14. Patient has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.\n15. Patient has active primary immunodeficiency, known uncontrolled active HIV infection or active hepatitis B or C (HBV\u002FHCV) infection. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. Subjects with past or resolved HBV infection are eligible only if they meet all of the following criteria:\n\n    * HBsAg(-) (for \\> 6 months off anti-viral treatment)\n    * Anti-HBc(+) (IgG or total Ig)\n    * HBV DNA undetectable\n    * Absence of cirrhosis or fibrosis on prior imaging or biopsy\n    * Absence of HCV co-infection or history of HCV co-infection\n    * Access to a local hepatologist during and after the study\n16. Patient has active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.\n17. Patient received treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is longer, prior to study enrollment.\n18. Patient received treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to study enrollment. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.\n19. Patient received prior allogeneic bone marrow transplantation or prior solid organ transplantation.\n20. Patient received live, attenuated vaccine within 30 days prior initiation of study drug.\n21. Patient has any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect.\n22. Patient participated in another interventional clinical study according to Medicines Act within 28 days prior to study enrollment or participation in a clinical study according to Medicines Act at the same time as this study unless it is an observational \u002F non-interventional study or during the follow-up period of an interventional study.\n23. Patient has taken an investigational drug within 28 days prior to initiation of study drug.\n24. Female patients, who are pregnant or breast feeding or planning to become pregnant within 7 months after the last dose of study treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.",{"count":338,"type":21},18,[340],"PHASE1","With this trial, we aim to evaluate a new combination therapy with tislelizumab and FLOT chemotherapy before surgery (neoadjuvant) for locally advanced, resectable adenocarcinoma of the esophagus or stomach (EGA). The aim of this phase Ib trial is to determine whether this combination is safe and clinically active enough to support the continuation of this concept in subsequent trials investigating novel drug combinations in the neoadjuvant setting of locally advanced EGA. As many patients are unable to tolerate the postoperative part of the standard therapy concept, we aim here to assess a prolongation of preoperative therapy to 6 or 8 applications of FLOT, instead of the routinely administered 4 pre- and 4 postoperative applications, in combination with tislelizumab.",[343,344,345,346,347],"Esophagogastric Junction Adenocarcinoma","Gastric Adenocarcinoma","Esophageal Adenocarcinoma","Resectable Esophagogastric Adenocarcinoma","Neoadjuvant Therapy",[349,350,351,201],"gastric cancer","FLOT","Tislelizumab","2025-12-12",{"date":354,"type":42},"2025-12-19",{"date":352,"type":42},{"date":357,"type":21},"2027-08",{"name":48,"class":49},4,{"id":361,"slug":362,"hasResults":11,"nctId":363,"briefTitle":364,"officialTitle":365,"acronym":4,"eligibilityCriteria":366,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":367,"targetDuration":4,"studyType":22,"phases":369,"briefSummary":370,"conditions":371,"keywords":4,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":373,"lastUpdatePostDateStruct":374,"startDateStruct":375,"completionDateStruct":377,"leadSponsor":379,"locationsCount":380},"100581940","phase-2---ikfaio-quintis---evaluating-fruquintinib-in-combination-with-tislelizumab-in-microsatellite-stable--proficient-mismatch-repair-msspmmr-metastatic-colorectal-cancer-without-active-liver-metastases-100581940","NCT06856837","- IKF\u002FAIO-QUINTIS - Evaluating Fruquintinib in Combination With Tislelizumab in Microsatellite Stable \u002F Proficient Mismatch Repair (MSS\u002FpMMR) Metastatic Colorectal Cancer Without Active Liver Metastases","- IKF\u002FAIO-QUINTIS - A Randomized Phase II Trial Evaluating Fruquintinib in Combination With Tislelizumab in Microsatellite Stable \u002F Proficient Mismatch Repair (MSS\u002FpMMR) Metastatic Colorectal Cancer Without Active Liver Metastases","Inclusion Criteria:\n\n1. Patient\\* provide signed informed consent form.\n2. Patient is ≥ 18 years at the time of given informed consent.\n3. Patient has been diagnosed with histologically or cytologically proven microsatellite stable (MSS)\u002Fproficient mismatch repair (pMMR) metastatic adenocarcinoma of the colon or rectum, which is not amenable to potentially curative resection.\n4. Known RAS (KRAS or NRAS) and BRAF V600E mutational status. Note: These mutations are mutually exclusive. Therefore, if one of the factors is mutated, it is not required to determine the mutation status of the others, as they are then assumed to be wildtype.\n5. Patient without liver metastases (NLM) defined as subjects without active liver metastases at screening as determined on baseline imaging of the liver as performed by CT scan with contrast or MRI. Definitively treated liver metastases (which includes surgical resection, microwave or radiofrequency ablation, or stereotactic body radiation therapy, but not yttrium-90 or chemoembolization alone) that were treated at least 3 months prior to enrollment with no evidence of radiologic progression on subsequent imaging are considered to be non-active liver metastases.\n6. Patient received at least one line of previous treatment with a fluoropyrimidine, oxaliplatin, irinotecan, VEGF(R) and if indicated EGFR and\u002For BRAF inhibitors in the advanced setting, or the patient has been intolerable or ineligible to those treatments.\n7. Patient has an ECOG performance status ≤ 1.\n8. Patient has a life expectancy \\> 16 weeks.\n9. Patient has adequate hematological, hepatic and renal function.\n\n   1. Absolute number of neutrophils (ANC) ≥ 1.5 x 109\u002FL\n   2. Platelets ≥ 100 x 109\u002FL\n   3. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) (or \\\u003C 2 x ULN in case of prior liver involvement or Gilbert's disease)\n   4. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN, AP ≤ 5 x ULN\n   5. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (measured by 24 h urine) ≥ 30 mL\u002Fmin (i.e., if serum creatinine level is \\> 1.5 x ULN, then a 24-hour urine test must be performed to check the creatinine clearance to be determined).\n   6. Urinary protein ≤2+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥3+, a 24-hour urine collection for protein must demonstrate \\\u003C2000 mg of protein in 24 hours to allow participation in this protocol)\n10. Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).\n11. Female patients of childbearing potential or male patients in Arm B with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year during the treatment period and for at least 6 months after the last trial treatment. Male patients in Arm B with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy. Female patients of child-bearing potential must have a negative pregnancy test within the last 7 days prior to the start of trial therapy.\n12. Patient is willing and able to comply with the protocol (including contraceptive measures) for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n\n    * There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the trial gender-independently.\n\nExclusion Criteria:\n\n1. Patient has known allergic \u002F hypersensitive reactions to at least one of the treatment components\n2. Patient had previous malignancy other than that under study within 3 years or concomitant malignancy, except: those with a 5-year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer\n3. Patient received previous treatment with Fruquintinib, trifluridine\u002Ftipiracil, regorafenib or an anti-PD-1\u002Fanti-PD-L1 antibodies.\n4. Patient receives current treatment with any anti-cancer therapy, such as systemic immunotherapy, chemotherapy, or hormone therapy within ≤ 2 weeks prior to study treatment start.\n5. Patient receives simultaneous treatment with a different anti-cancer therapy other than that provided for in the trial (excluding palliative radiotherapy for symptom control).\n6. Patient has known untreated or symptomatic CNS or leptomeningeal metastases.\n7. Patient has impaired cardiac function or clinically significant cardiac disease including unstable angina within 6 months before the first dose of study treatment, acute myocardial infarction \\\u003C 6 months prior to the first dose of study treatment, New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolled hypertension (defined as an average systolic blood pressure \\> 160 mmHg or diastolic \\> 100 mmHg despite optimal treatment, uncontrolled cardiac arrhythmias requiring antiarrhythmic therapy other than beta blockers or digoxin, active coronary artery disease or corrected QT interval (QTc) ≥ 470.\n8. Patient has history of uncontrolled infection with human deficiency virus (HIV) or chronic infection with hepatitis B or C virus (HBV, HCV).\n9. Patient has evidence of bleeding diathesis.\n10. Patient has history of gastrointestinal perforation or fistulae in past 6 months or risk factors for perforation.\n11. Patient has grade 3-4 gastrointestinal bleeding within 3 months prior to first dose of trial therapy.\n12. Use of strong inducers or inhibitors of CYP3A4 within 2 weeks (or 5 half-lives, whichever is longer) before the first dose of study drug (see Appendix 4 for examples).\n13. Patient had a major surgery within 2 weeks prior to first dose of trial therapy.\n14. Patient experienced severe, life-threatening, or recurrent (Grade 2 or higher) immune-mediated adverse events (AEs) or infusion-related reactions including those that led to permanent discontinuation while on treatment with immune-oncology agents.\n15. Patient received prior immunosuppressive therapy: immunosuppressive doses of systemic medications of \\> 10 mg\u002Fday of prednisone or equivalent must be discontinued ≥ 2 weeks before the first dose of study treatment. Short courses of high dose corticosteroids and\u002For continuous low dose of prednisone (\\\u003C 10 mg\u002Fday) are permitted. In addition, inhaled, intranasal, intraocular, and\u002For joint injections of corticosteroids are allowed.\n16. Patient has active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study.\n17. Patient has history of solid organ transplantation .\n18. Patient has history of thromboembolic events (including deep vein thrombosis and pulmonary embolism) within the past 6 months or history of stroke and\u002For transient ischemic attack within the last 12 months.\n19. Patients has evidence of any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect.\n20. Female patient is pregnant or breast feeding or planning to become pregnant within and up to 6 months after end of treatment.",{"count":368,"type":21},140,[24],"This is a prospective, randomized, open-label, multicenter phase II investigating the therapy of Fruquintinib in combination with Tislelizumab in patients with MSS\u002FpMMR metastatic colorectal cancer without liver metastases.",[372],"Metastatic Colorectal Cancer","2025-12-05",{"date":352,"type":42},{"date":376,"type":42},"2025-10-27",{"date":378,"type":21},"2029-12-31",{"name":48,"class":49},23,{"id":382,"slug":383,"hasResults":11,"nctId":384,"briefTitle":385,"officialTitle":386,"acronym":4,"eligibilityCriteria":387,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":388,"targetDuration":4,"studyType":22,"phases":390,"briefSummary":391,"conditions":392,"keywords":4,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":395,"lastUpdatePostDateStruct":396,"startDateStruct":398,"completionDateStruct":400,"leadSponsor":402,"locationsCount":328},"100549971","phase-2-durvalumab--intraductal-radiofrequency-ablation-id-rfa-in-extrahepatic-cholangiocarcinoma-100549971","NCT06440993","Durvalumab + Intraductal Radiofrequency Ablation (ID-RFA) in Extrahepatic Cholangiocarcinoma","The CLEAN-DUCT \u002F TRITICC-3 Trial - Phase IIa, Prospective, Single Arm, Open Label, Non-randomized, Multi-center Pilot Study of Durvalumab (MEDI4736) + Intraductal Radiofrequency Ablation (ID-RFA) in Extrahepatic Cholangiocarcinoma","Inclusion Criteria:\n\n1. Patient\\* has given written informed consent.\n2. Patient is ≥ 18 years of age at time of signing the written informed consent.\n3. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n4. Patient has been diagnosed with histologically or cytologically confirmed\n\n   1. histologically or cytologically confirmed cholangiocarcinoma as adenocarcinoma of pancreatobiliary type\n   2. unresectable perihilar and\u002For ductal cholangiocarcinoma with indication for bile duct stenting and palliative systemic therapy as determined by the local multidisciplinary team (MDT) and already resolved cholestasis due to RFA + stent\n5. Patient tolerated RFA prior to inclusion and is eligible for repeat RFA during the study (does not have any contraindications) as determined by investigator.\n6. Patient is eligible for palliative systemic therapy based on clinical and laboratory parameters (except hyperbilirubinemia) as determined by the local MDT\n7. Patient has a ECOG ≤ 1.\n8. Patient has life expectancy of ≥ 12 weeks\n9. Patient has body weight \\> 30 kg\n10. Adequate blood count, liver-enzymes, and renal function:\n\n    1. ANC \\> 1,500 cells\u002FμL without the use of hematopoietic growth factors\n    2. Platelet count ≥ 100 x 109\u002FL (\\>100,000 per mm3)\n    3. Hemoglobin ≥ 9 g\u002FdL\n    4. Serum total bilirubin ≤ 3x upper normal limit (ULN) (biliary drainage is allowed for biliary obstruction; elevated bilirubin should be caused by obstruction not impaired liver function as assessed by albumin and INR values)\n    5. Albumin levels ≥ 2.8 g\u002FdL\n    6. Patients not receiving therapeutic anticoagulation must have an INR\\\u003C 2.0 ULN and PTT \\\u003C 1.5 ULN within 7 days prior to randomization. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of inclusion\n    7. AST (SGOT)\u002FALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present, in which case it must be ≤ 5x ULN\n    8. Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate ≥ 60 mL \u002Fmin\n11. Female patients defined as women of childbearing potential (WOCBP) or male patients with WOCBP partners must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C1% per year during the treatment period and for at least 6 months after the last dose of chemotherapy or for at least 3 months after last dose of durvalumab, whatever happens last. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.\n\nExclusion Criteria:\n\n1. Patient received previous or simultaneous endobiliary treatment other than RFA (e.g. PDT or brachytherapy)\n2. Patient received previous systemic therapy with a PD-1, PD-L1 inhibitor (including durvalumab) or CTLA4 inhibitor or classical chemotherapy agents like platinum, fluoropyrimidine or gemcitabine-based regimens.\n3. Patient receives any concurrent chemotherapy, investigational product or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replace therapy) is acceptable.\n4. Patient has known hypersensitivity to any component of the durvalumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein and\u002For any known contraindication (including hypersensitivity) to gemcitabine or cisplatin.\n5. Patient has history of primary immunodeficiency\n6. Patient has stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.\n7. Patient has any unresolved NCI CTCAE grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and laboratory values defined in the inclusion criteria\n\n   1. Patients with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Lead Investigator\n   2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Lead Investigator.\n8. Patient had a prior allogeneic bone marrow transplantation or prior solid organ transplantation.\n9. Patient has active or history of autoimmune or inflammatory disorders (including, but not limited to, inflammatory bowel disease \\[e.g., colitis or Crohn's disease\\], diverticulitis \\[with the exception of diverticulosis\\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis\\]) . The following are exceptions:\n\n   1. Patients with vitiligo or alopecia\n   2. Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement\n   3. Patients with any chronic skin condition that does not require systemic therapy\n   4. Patients with celiac disease controlled by diet alone\n   5. Patients without active disease in the last 5 years may be included but only after consultation with the Lead Investigator\n10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent",{"count":389,"type":21},42,[24],"The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter phase II trial. Patients with unresectable perihilar and\u002For ductal CCA with indication for bile duct stenting and palliative systemic therapy as determined by the local multidisciplinary team (MDT), who already resolved cholestasis due to RFA + Stent will be enrolled.\n\nWe hypothesize that in patients with extrahepatic cholangiocarcinoma, the use of a combination radiofrequency ablation followed by systemic treatment with chemotherapy plus durvalumab might further increase the anti-tumor activity.",[393,394],"Extrahepatic Cholangiocarcinoma","Unresectable Perihilar or Ductal CCA","2025-11-28",{"date":397,"type":42},"2025-12-01",{"date":399,"type":42},"2024-08-23",{"date":401,"type":21},"2028-04",{"name":48,"class":49},{"id":404,"slug":405,"hasResults":11,"nctId":406,"briefTitle":407,"officialTitle":408,"acronym":4,"eligibilityCriteria":409,"healthyVolunteers":11,"sex":410,"minAge":18,"maxAge":4,"enrollmentInfo":411,"targetDuration":4,"studyType":22,"phases":413,"briefSummary":414,"conditions":415,"keywords":417,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":421,"lastUpdatePostDateStruct":422,"startDateStruct":424,"completionDateStruct":426,"leadSponsor":428,"locationsCount":429},"100532048","phase-2-discontinuation-of-cdk46-inhibitors-in-patients-with-metastatic-hr-positive-her2-negative-breast-cancer-100532048","NCT06207734","Discontinuation of CDK4\u002F6 Inhibitors in Patients With Metastatic HR Positive, HER2 Negative Breast Cancer","Discontinuation of CDK4\u002F6 Inhibitors in Patients With Metastatic HR Positive, HER2 Negative Breast Cancer With Durable Disease Control: A Randomized Low-intervention Phase II Trial of the AIO Working Groups Breast Cancer and Quality of Life","Inclusion Criteria:\n\n1. Female patient has given written informed consent\n2. Patient is ≥ 18 years of age at time of signing the written informed consent\n3. Patient has been diagnosed with histologically confirmed metastatic adenocarcinoma of the breast\n4. Patient has documented histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative (HER2-) disease\n5. Patient has no curative treatment option by surgery or radiotherapy\n6. Patient was treated with CDK4\u002F6 inhibitor plus endocrine therapy for at least 12 months with disease control (complete remission, partial remission or stable disease) as judged by the treating physician before planned study treatment initiation\n7. Patient has a preserved performance status (ECOG ≤ 2)\n8. Patient has adequate bone marrow, renal and hepatic function:\n\n   1. Hemoglobin \\> 9.0 g\u002FdL\n   2. Absolute neutrophil count judged as appropriate for study therapy by the investigator\n   3. Platelets ≥ 100 x 109\u002FL\n   4. Calculated creatinine clearance judged as appropriate for study therapy by the investigator\n   5. AST (SGOT) \u002F ALT (SGPT) and alkaline phosphatase ≤ 2.5x ULN\n   6. Serum albumin \\> 30 g\u002FL\n9. Patients considered postmenopausal according to one of the following definition:\n\n   1. Women \\\u003C50 years of age who are amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and whose levels of luteinizing hormone and follicle-stimulating hormone are in the post-menopausal institutional range\n   2. Women ≥50 years of age who are amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \\>1 year ago or had chemotherapy-induced menopause with last menses \\>1 year ago\n   3. Artificially induced postmenopausal women (by Gonadotropin-releasing hormone \\[GnRH\\] analogs)\n10. WOCBP must have a negative serum pregnancy test within 7 days prior to start of trial\n\nExclusion Criteria:\n\n1. Patient has active (or history of) brain or leptomeningeal metastases\n2. Patient is pre- or perimenopausal. Patient is pregnant or breast feeding or planning to become pregnant within five times the half-life of the IMPs after the end of treatment.\n3. Patient has significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 6 months prior to initiation of study treatment, unstable arrhythmias, or unstable angina\n4. Patient has other concomitant or previous malignancy, except adequately treated in-situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, cancer in complete remission for \\> 5 years\n5. Patient has contraindication or shows hypersensitivity to the existing treatment with CDK4\u002F6 inhibitor plus endocrine therapy\n6. Patient shows evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results\n7. Patient participated in another clinical study with an investigational medicinal product during the last 28 days before treatment initiation or 7 half-lives of previously used trial medication, whichever is longer or participate in such a study at the same time as this trial.\n\n   Note: Participation in non-interventional clinical studies or registries is allowed.\n8. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study.\n9. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.\n10. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts.","FEMALE",{"count":412,"type":21},120,[24],"This is a low-intervention, randomized, non-comparative, open-label, multicenter, prospective, phase II trial investigating discontinuation of CDK4\u002F6 inhibitors in patients with metastatic HR positive, HER2 negative breast cancer with durable disease control.",[416],"Breast Cancer",[418,419,420],"Metastatic HR positive, HER2 negative breast cancer","CDK4\u002F6 inhibitors","Endocrine therapy","2025-04-30",{"date":423,"type":42},"2025-05-01",{"date":425,"type":42},"2024-01-17",{"date":427,"type":21},"2028-07-10",{"name":48,"class":49},13,{"id":431,"slug":432,"hasResults":11,"nctId":433,"briefTitle":434,"officialTitle":435,"acronym":4,"eligibilityCriteria":436,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":437,"targetDuration":4,"studyType":22,"phases":439,"briefSummary":441,"conditions":442,"keywords":444,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":450,"lastUpdatePostDateStruct":451,"startDateStruct":453,"completionDateStruct":455,"leadSponsor":457,"locationsCount":458},"100424215","phase-3-the-abc-hcc-trial-atezolizumab-plus-bevacizumab-vs-transarterial-chemoembolization-tace-in-intermediate-stage-hepatocellular-carcinoma-100424215","NCT04803994","The ABC-HCC Trial: Atezolizumab Plus Bevacizumab vs. Transarterial Chemoembolization (TACE) in Intermediate-stage HepatoCellular Carcinoma","The ABC-HCC Trial: A Phase IIIb, Randomized, Multicenter, Open-label Trial of Atezolizumab Plus Bevacizumab Versus Transarterial Chemoembolization (TACE) in Intermediate-stage HepatoCellular Carcinoma","Inclusion Criteria:\n\n1. Signed Informed Consent Form available\n2. Patients\\* ≥ 18 years of age at time of signing Informed Consent Form\n3. Confirmed hepatocellular carcinoma diagnosis based on histopathological findings from tumor tissue or typical diagnostic imaging on dynamic CT or MRI according to AASLD criteria.\n4. Intermediate stage HCC as defined by the following criteria:\n\n   * Disease not amenable to curative surgery, liver transplantation or curative ablation BUT disease amenable to TACE at enrollment as judged by the investigator.\n   * No massive multinodular pattern preventing adequate TACE\n   * No tumor of a diffuse infiltrative HCC type (hypovascular infiltrative tumors with ill-defined borders)\n   * Patent portal vein flow\n   * No main portal vein invasion\u002Fthrombosis on baseline\u002Feligibility imaging. Patients with minimal invasion, (Vp1 and Vp2) may be eligible if no exclusion criteria are violated.\n   * No extrahepatic disease Note: Patients with HCC beyond Milan criteria who enter a downstaging protocol may be recruited into the trial if they do not present any exclusion criteria.\n5. Patients with recurrence after resection\u002Fablation or after previous TACE are eligible, if they - according to the investigator - have an indication for (additional) TACE\n6. Child-Pugh score class A or B7 without ascites requiring more than 100 mg of spironolactone\u002Fday (see exclusion criteria) at enrollment.\n7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at enrollment.\n8. Adequate organ and bone marrow function\n9. Life expectancy of ≥ 3 months\n10. The following laboratory values obtained less than or equal to 7 days prior to randomization.\n\n    * Total bilirubin ≤ 3.0 x the upper limit of normal (ULN)\n    * Urine dipstick for proteinuria ≤ 2+ (within 7 days prior to randomization) Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \\\u003C 1 g of protein in 24 hours\n    * The following other laboratory values measured within 7 days prior to randomization are either normal or if abnormal do not represent a medical contraindication for TACE and atezolizumab\u002Fbevacizumab as judged by the investigator: Platelet count, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine, INR or aPTT, alkaline phosphatase, neutrophil count (ANC), and serum albumin.\n11. Negative serum pregnancy test done lesser than or equal to 7 days prior to randomization, for females of childbearing potential only.\n12. No presence of untreated or incompletely treated varices with bleeding or high-risk for bleeding: Availability of esophagogastroduodenoscopy (not older than 6 months) in which all size of varices (small to large) had been assessed and varices were treated per local standard of care prior to randomization.\n13. Absence of other severe comorbidities\n14. Resolution of any acute, clinically significant treatment-related adverse events from prior therapy\u002Fprocedure to Grade ≤ 1 prior to randomization, with the exception of alopecia.\n15. For patients with active hepatitis B virus (HBV):\n\n    * HBV DNA ≤ 2000 IU\u002FmL obtained within 28 days prior to randomization, AND\n    * Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study.\n16. For patients with active hepatitis C virus (HCV):\n\n    * Patients positive for hepatitis C virus (HCV) antibody are eligible, also if polymerase chain reaction testing is positive for HCV ribonucleic acid (RNA).\n    * However, anti-viral therapy against HCV is only allowed prior to trial but not during the trial.\n    * For HBV and HCV co-infection refer to exclusion criterion # 11.\n17. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \\\u003C 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last TACE procedure.\n\n    * A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and\u002For uterus).\n    * Examples of contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.\n    * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\n18. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:\n\n    * With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \\\u003C 1% per year during the treatment period and for 6 months after the last dose of bevacizumab or 1 month after the last TACE procedure. Men must refrain from donating sperm during this same period.\n    * With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of bevacizumab or 1 month after the last TACE procedure to avoid exposing the embryo.\n    * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\n\n      * There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.\n\nExclusion Criteria:\n\n1. 1\\. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC (only if proven by biopsy).\n2. Previous treatment with atezolizumab or bevacizumab.\n3. Previous treatment with a programmed death 1 (PD1), programmed death-ligand (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of cancer immunotherapy for HCC.\n4. Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control.\n\n   • Patients with ascites requiring pharmacologic intervention (e.g. diuretics) and stable for ≥ 2 months on low doses of diuretics (spironolactone 100 mg\u002Fd or equivalent) for ascites are eligible. Of note, diuretics for other indications such as congestive heart failure are not considered in this regard.\n5. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days prior to randomization or anticipation of need for major surgical procedure during the course of the study or non-recovery from side effects of any such procedure.\n6. Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, as well as unstable arrhythmias (note: beta blockers or digoxin are permitted), unstable angina, new-onset angina (begun within the last 3 months).\n7. Uncontrolled hypertension defined by a systolic blood pressure (BP) ≥ 150 mmHg or diastolic blood pressure (BP) ≥ 100 mmHg, with or without antihypertensive medication. Prior history of hypertensive crisis or hypertensive encephalopathy. Patients with initial blood pressure (BP) elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria.\n8. Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose (prophylactic anticoagulation permitted, e.g. new oral anticoagulants \\[apixaban, dabigatran, rivaroxaban\\], LMW heparin, ASA up to 300 mg\u002Fqd).\n9. Arterial or venous thrombotic or embolic events such as cerebro-vascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism ≤6 months prior to randomization.\n10. With regards to eligibility for adequate TACE, patients presenting with either of the following conditions are excluded:\n\n    * Past history of bilioenteric anastomosis or biliary procedure (e.g., endoscopic papillotomy or biliary stenting) or patients with aerobilia\n    * Central biliary obstruction (right or left intrahepatic duct, common hepatic duct, common bile duct)\n    * Celiac occlusion\n11. Any ongoing infection \\> grade 2 NCI-CTCAE version 5.0. Note on HIV, HBV, and HCV infection: also consider inclusion criteria #s 15, 16, and exclusion criterion # 18. Patients with co-infection for HBV and HCV are excluded, unless tested negative for HCV RNA by PCR.\n12. Patients with seizure disorder requiring medication.\n13. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.\n14. Evidence or history of bleeding diathesis or any hemorrhage or bleeding event \\> CTCAE grade 3 within 4 weeks prior to randomization.\n15. Non-healing wound, ulcer, or bone fracture.\n16. Renal failure requiring hemo- or peritoneal dialysis.\n17. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation including a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein; known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation.\n18. Positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), with the following exception: patients with a positive HIV test at screening are eligible, provided they are stable on anti-retroviral therapy, have a CD4 count \\> 200 cells\u002FµL, and have an undetectable viral load.\n19. Active tuberculosis\n20. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.\n21. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan Note: History of radiation pneumonitis within the radiation field (fibrosis) is permitted.\n22. Persistent proteinuria of CTCAE Grade 3 or higher (\\> 3.5 g\u002F24 hrs, measured by urine protein: creatinine ratio on a random urine sample).\n23. Pregnant or nursing women\n24. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.\n25. Active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.\n\n    Note: History of autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone, or controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible based on consultation with the sponsor's medical monitor. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:\n    * Rash must cover \\\u003C 10% of body surface area\n    * Disease is well controlled at baseline and requires only low-potency topical corticosteroids\n    * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.\n26. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:\n\n    * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.\n    * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.\n27. Use of any herbal remedies known to interfere with the liver or other major organ functions. Patients must notify the investigator of all herbal remedies used during the study.\n28. Administration of a live, attenuated vaccine within four weeks prior to start of enrollment, or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last TACE procedure.\n29. History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate \\> 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. Other similar cases can be considered after discussion with lead investigators and sponsor.\n30. Receipt of an investigational drug within 28 days prior to initiation of study drug\n31. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent or patients with substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.",{"count":438,"type":21},434,[440],"PHASE3","The ABC-HCC trial is a Phase IIIb, randomised, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab plus bevacizumab versus TACE in patients with intermediate-stage HCC. Approximately 434 patients in two arms of treatment will be enrolled.",[443],"Hepatocellular Carcinoma",[445,258,446,447,448,449],"hepatocellular carcinoma","intermediate stage","atezolizumab","bevacizumab","TACE","2025-01-06",{"date":452,"type":42},"2025-01-07",{"date":454,"type":42},"2021-07-06",{"date":456,"type":21},"2027-07",{"name":48,"class":49},72,{"id":460,"slug":461,"hasResults":11,"nctId":462,"briefTitle":463,"officialTitle":464,"acronym":4,"eligibilityCriteria":465,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":466,"targetDuration":4,"studyType":22,"phases":468,"briefSummary":469,"conditions":470,"keywords":472,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":475,"lastUpdatePostDateStruct":476,"startDateStruct":478,"completionDateStruct":480,"leadSponsor":482,"locationsCount":483},"100494104","phase-2-organ-preservation-with-durvalumab-based-immunotherapy-in-combination-with-chemoradiation-as-definitive-therapy-for-early-stage-esophageal-adenocarcinoma-with-indication-for-radical-surgery-100494104","NCT05713838","Organ Preservation With Durvalumab-based Immunotherapy in Combination With Chemoradiation as Definitive Therapy for Early Stage Esophageal Adenocarcinoma With Indication for Radical Surgery","Organ Preservation With Durvalumab-based Immunotherapy in Combination With Chemoradiation as Definitive Therapy for Early Stage, cT1 and cT2N0, Esophageal Adenocarcinoma With Indication for Radical Surgery: A Prospective, Multicenter Study of the FLOT-AIO Gastric Cancer Group","Inclusion Criteria:\n\n1. Patient has given written informed consent.\n2. Patient is, in the investigator's judgement, willing and able to comply with the study protocol including the planned surgical treatment.\n3. Patient is ≥ 18 years of age at time of signing the written informed consent.\n4. Patient has been diagnosed with histologically confirmed esophageal adenocarcinoma (including gastroesophageal junction (GEJ) (Siewert I-III)) with:\n\n   1. cT2 N0 M0 stage or T1 N0 M0 stage and a given indication for radical surgical resection to current S3-guidelines (this includes patients with a given indication for radical surgery after endoscopic-resection of a cT1-2 N0 M0 tumor \\[poor grading or L1\u002FV1 invasion or basal R1 resection or deep submucosal infiltration\\]) (see section 4.2.3 for detailed information).\n   2. tumor is considered medically and technically resectable.\n5. Tumor is tested (local testing with validated assays is sufficient, e.g., Dako PD-L1 IHC 22C3 or 28-8) for PD-L1 according to combined positive score (CPS) and results must be available prior study enrollment. In addition, tumor should be tested locally for MSI status and PD-L1 according to tumor proportion score (TPS) OR a representative tumor specimen that is suitable for central determination of PD-L1 TPS and MSI status is available. The analysis requires paraffin embedded biopsy samples of the tumor to be provided to the Sponsor.\n\n   NOTE: It is encouraged that CPS, TPS and MSI testing is performed in parallel locally at the trial site prior to enrollment, but at least CPS per local testing has to be available prior to enrollment.\n6. Patient has not received prior cytotoxic or targeted therapy.\n7. Patient has not had a prior complete esophagogastric tumor resection.\n8. Patient has a ECOG ≤ 1.\n9. Patient must have life expectancy of at least 12 weeks\n10. Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\<1% per year during the treatment period and for at least 6 months after the last study treatment if it is in the core treatment phase or for at least 3 months after last study treatment occurred in the maintenance phase. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.\n11. Patient has a body weight \\> 30 kg\n12. Patient has adequate hematological, hepatic and renal function as indicated by the following parameters:\n\n    1. Leukocytes ≥ 3,000\u002FµL, platelets ≥ 100,000\u002FµL without transfusion, absolute neutrophil count (ANC) ≥ 1,500\u002FµL without granulocyte colony-stimulating factor support, hemoglobin ≥ 90 g\u002FL (9 g\u002FdL) - Patients may be transfused to meet this criterion.\n    2. Bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate transaminase and alanine transaminase ≤ 2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN\n    3. Serum creatinine ≤ 1.5 x ULN, or glomerular filtration rate \\> 45 mL\u002Fmin (calculated using the Cockcroft-Gault formula)\n    4. Serum albumin ≥ 25 g\u002FL (2.5 g\u002FdL)\n    5. For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN; for patients receiving therapeutic anticoagulation: stable anticoagulant regimen\n13. Patient has no human immunodeficiency virus (HIV) infection. NOTE: Patient with infection is eligible if he\u002Fshe meets all the following criteria:\n\n    1. CD4 count is ≥350 cells\u002FµL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications\n    2. Probable long-term survival with HIV if cancer were not present\n    3. Stable on a highly active antiretroviral therapy (HAART) regimen for ≥4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study\n    4. HIV is not multi-drug resistant\n    5. Taking medication and\u002For receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication\n\nExclusion Criteria:\n\n1. Patient has known hypersensitivity to any component of the durvalumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.\n2. Patient has any known contraindication (including hypersensitivity) to docetaxel, 5-FU, leucovorin (calcium folinate), or oxaliplatin. In cases of pernicious anemia or other anemias due to vitamin B 12 deficiency, folinic acid (Leucovorin) is contraindicated and trial inclusion is not possible or only possible after compensation the anaemic status.\n3. Patient has a known dihydropyrimidine dehydrogenase (DPD) deficiency. Patients with reduced DPD activity (CPIC activity score of 1.0-1.5) might participate in the study and receive a reduced dosage of 5-FU.\n4. Patient has active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.\n\n   NOTE: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone, or controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible based on consultation with the sponsor's medical monitor. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all following conditions are met:\n   * Rash must cover \\< 10% of body surface area.\n   * Disease is well controlled at baseline and requires only low-potency topical corticosteroids.\n   * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.\n5. Patient had a prior allogeneic bone marrow transplantation or prior solid organ transplantation.\n6. Patient has a history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.\n\n   NOTE: History of radiation pneumonitis within the radiation field (fibrosis) is permitted.\n7. Patient has active hepatitis B (defined as having a positive hepatitis B surface antigen \\[HBsAg\\] test prior to enrollment) or hepatitis C infection NOTE: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA).\n8. Patient has active tuberculosis.\n9. Patient has uncontrolled tumor-related pain (Patients requiring pain medication must be on a stable regimen at study entry.)\n10. Patient received an administration of a live, attenuated vaccine within four weeks prior to start of enrollment, or anticipation that such a live attenuated vaccine will be required during the study or within 30 days after the last dose of durvalumab.\n11. Patient had a prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibodies.\n12. Patient had a treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is longer, prior to study enrollment.\n13. Patient had a treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed\n\n    1. Intranasal, inhaled, topical steroids or local steroid injections (e.g. intra articular injection)\n    2. Systemic corticosteroids at physiologic dose not to exceed 10mg\u002Fday of prednisone or its equivalent\n    3. Steroids as premedication for hypersensitivity reactions (e.g. CT premedication)\n14. Patient has a significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmias, or unstable angina.\n15. Patient has a clinically significant valvular defect.\n16. Patient has a history of malignancy other than EGA within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate \\>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.\n17. Patient has peripheral polyneuropathy ≥ NCI CTCAE grade 2.\n18. Patient has uncontrolled or symptomatic hypercalcemia (ionized calcium \\> 1.5 mmol\u002FL, calcium \\> 12 mg\u002FdL or corrected serum calcium \\> ULN).\n19. Patient has a serious infection requiring oral or IV antibiotics within 14 days prior to study enrollment.\n20. Patient has chronic inflammatory bowel disease.\n21. Patient has clinically significant active gastrointestinal bleeding.\n22. Patient underwent major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment.\n23. Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results.\n24. Patient participated in another interventional clinical study ≤ 30 days prior to study enrollment or participation in such a study at the same time as this study.\n25. Patient has taken an investigational drug within 28 days prior to initiation of study drug.\n26. Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.",{"count":467,"type":21},32,[24],"The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter phase II trial investigating whether a definite organ preservation therapy consisting of the combination of durvalumab with chemoradiation is an efficient and safe treatment option for early stage, cT1 and cT2N0, esophageal adenocarcinoma with indication for radical surgery.",[471],"Esophagus Adenocarcinoma",[473,474],"esophageal adenocarcinoma","GEJ adenocarcinoma","2024-09-03",{"date":477,"type":42},"2024-09-19",{"date":479,"type":42},"2023-08-28",{"date":481,"type":21},"2028-12",{"name":48,"class":49},22,""]