[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"radiation-necrosis\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:radiation-necrosis":150},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,60,85,113,137],{"id":9,"slug":4,"hasResults":10,"nctId":11,"briefTitle":12,"officialTitle":13,"acronym":14,"eligibilityCriteria":15,"healthyVolunteers":10,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":33,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":48,"lastUpdatePostDateStruct":49,"startDateStruct":52,"completionDateStruct":54,"leadSponsor":56,"locationsCount":59},"100053384",false,"NCT06888817","Bevacizumab Versus Corticosteroids as First-line Treatment in Patients With Symptomatic Cerebral Radiation Necrosis After Radiation for High-grade Glioma or Brain Metastases","Bevacizumab for the Treatment of Cerebral RAdiation Induced NecrosiS (BRAINS) Study: a Multicenter, Open-label, Randomized Clinical Trial to Assess the Clinical Efficacy and Cost-effectiveness of Bevacizumab Versus Corticosteroids as First-line Treatment in Patients With Symptomatic Cerebral Radiation Necrosis After Radiation for High-grade Glioma or Brain Metastases","BRAINS","Inclusion Criteria:\n\nInclusion all patients (both HGG and BM):\n\n1. Age ≥ 18 years old\n2. First episode of sCRN ≥ 3 months after completion of focal (re-)irradiation, as determined by the local Multidisciplinary Neuro-Oncology Board. A clear working diagnosis of CRN without evidence of a combination with tumour progression is required\n3. KPS score ≤ 90 and either (a) a minimum loss of two points in at least one domain of the Neurologic Assessment in Neuro-Oncology (NANO) scale as compared to the maximum score of that domain due to sCRN, or (b) a headache attributable to sCRN with an average intensity ≥5\u002F10 on the NRS, persisting for ≥10 consecutive days, with inadequate relief despite an adequate trial of paracetamol and\u002For an NSAID unless these medications are contra-indicated or not tolerated\n4. Maximum daily dexamethasone use of 1 mg\u002Fday for the 8 weeks preceding randomization\n\n   1. Dexamethasone may have been prescribed for various indications, except for managing (ongoing) cerebral edema\n   2. Higher doses of dexamethasone are permitted 3 weeks immediately preceding randomization if used specifically for the treatment of sCRN\n5. Able to understand the patient information, online tests and questionnaires\n6. Written informed consent\n\nInclusion BM:\n\n1\\. BM of solid tumour, including all primary tumour types\n\nInclusion HGG:\n\n1\\. A confirmed histological diagnosis of high-grade diffuse glioma according to WHO 2021 criteria, including: astrocytoma, IDH-mutant, grade 3-4; astrocytoma, IDH-wildtype (sybtype molecular glioblastoma); oligodendroglioma, 1p\u002F19q codeleted, grade 3; diffuse glioma, NEC, grade 3-4; or glioblastoma, IDH-wildtype, grade 4\n\nExclusion Criteria:\n\nA potential subject who meets any of the following criteria will be excluded from participation in this study, both for the BM and HGG group:\n\n1. Prior treatment with bevacizumab \\\u003C6 months before diagnosis of sCRN\n2. Life expectancy \\\u003C3 months\n3. Impending radiological or clinical signs of brain herniation necessitating immediate decompressive surgery\n4. Any comorbidity or condition that prevents safe administration of the studied medication, determined by the treating physician, including but not limited to:\n\n   1. Intolerance for murine proteins\n   2. Hypersensitivity or allergy to the active substance or to any of the excipients of bevacizumab or dexamethasone\n   3. Nephrotic syndrome or abnormal renal function\n\n      o Calculated (Cockcroft-Gault) or measured creatinine clearance \\\u003C30 mL\u002Fmin; urine dipstick for proteinuria ≥ 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hours urine collection and must demonstrate ≤ 1 g of protein\u002F24 hr.\n   4. Clinical significant cardiovascular disease\n\n      * Uncontrolled hypertension (systolic BP \\>150mmHg and\u002For diastolic \\>100mmHg) despite the use of ≥ 3 antihypertensive drugs\n      * Previous hypertensive crisis, hypertensive encephalopathy or previous reversible posterior leukoencephalopathy syndrome (RPLS)\n      * Non tumour related vascular event (e.g. cerebral or cardiac ischemia\u002Fbleeding (including transient ischemic attack, cerebral ischemia, unstable angina or angina requiring intervention, myocardial infarction), peripheral arterial thrombus, peripheral artery disease, deep venous thrombosis, lung embolism) \\\u003C 6 months\n      * History of aortic aneurysm or dissection\n      * Congestive heart failure NYHA II-IV\n   5. History of gastro-intestinal fistula, perforation or abscess \\\u003C 6 months\n   6. History of bleeding\n\n      * Relevant pulmonary hemorrhage\u002F hemoptysis \\\u003C 1 month or the presence of a pulmonary lesion with a high risk of bleeding (= central lung tumour and\u002For untreated squamous cell carcinoma) according to the treating physician\n      * Active gastrointestinal bleeding \\\u003C 6 months\n      * Evidence of recent intracranial hemorrhage on MRI brain \\\u003C3 months. Asymptomatic presence of hemosiderin depositions or punctate hemorrhage in the tumour do not serve as a ground for exclusion\n   7. Excess risk of bleeding\n\n      * History or evidence of inherited bleeding diathesis or significant coagulopathy with the risk of bleeding\n      * Decreased platelet count \\\u003C 75x109\u002FL\n   8. Risk of wound healing complications\n\n      * Significant non-healing wound, (peptic) ulcer or bone fracture\n      * Major surgical procedure (including open biopsy) or significant traumatic injury within 28 days prior to first study treatment or planned surgical procedure within the following next 28 days after planned study inclusion\n      * Minor surgical procedure, stereotactic\u002Fcore biopsy, fine needle aspiration within 7 days prior to first study treatment\n   9. High-dose radiotherapy to the mediastinum, abdomen, or lower pelvis; administration of bevacizumab should only be considered after prior consultation with a pulmonologist or oncologist\n   10. Pregnancy or lactation. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of HCG) within 7 days prior to randomization. WOCBP and female partners of male patients must comply with adequate contraception methods as requested by the study protocol\n   11. Evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the study treatment, affect patient compliance or place the patient at high risk for treatment-related complications according to the treating physician\n   12. Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another interventional study In case of uncertainty, consult the principal investigator of the study site.","ALL","18 Years",{"count":19,"type":20},408,"ESTIMATED","INTERVENTIONAL",[23],"PHASE3","Cerebral radiation necrosis (CRN) is a severe complication of high-dose radiation for brain metastases (BM) or glioma, which can potentially cause significant neurologic symptoms leading to serious morbidity and impaired quality of life (QoL). The first-line therapy for symptomatic CRN (sCRN) is corticosteroids, primarily dexamethasone, which often leads to complications, refractory symptoms, and interference with anti-cancer treatment. Since 2017, bevacizumab, an antibody against Vascular Endothelial Growth Factor (VEGF), has been used in a second-line treatment setting for refractory sCRN. A small randomized clinical trial (RCT) has shown that bevacizumab significantly diminishes cerebral edema on MRI and decreases clinical symptoms of sCRN in irradiated glioma patients. Several non-randomized clinical studies demonstrated a beneficial radiological and clinical effect of bevacizumab in patients with sCRN after irradiation for BM. The optimal first-line treatment for sCRN is currently unknown. Effective and safe first-line treatment of sCRN will optimize the patient's well-being and health-related QoL. Furthermore, minimizing corticosteroid use will benefit the clinical treatment options and outcomes of concomitant or future anti-cancer treatment. This phase III multicenter, open-label, randomized clinical trial compares the clinical efficacy of first-line bevacizumab versus standard-of-care dexamethasone for sCRN in patients with high-grade glioma (HGG) or BM.",[26,27,28,29,30,31,32],"Radiation Necrosis","High Grade Glioma (III or IV)","Brain Metastasases","Radiation Toxicity","Radiation Effect","Radiation Injury","Radiation Injuries",[34,35,36,37,38,39,40,41,42,43,44,45,46],"Cerebral radiation necrosis","High Grade Glioma","Brain Metastases","Bevacizumab","Dexamethasone","Randomized Clinical Trial","First-line treatment","Anti-VEGF monocolonal antibody","Corticosteroids","Radiation induced necrosis","Radiation effects","Radiation injury","Radiation toxicity","RECRUITING","2026-07-09",{"date":50,"type":51},"2026-07-13","ACTUAL",{"date":53,"type":51},"2025-06-19",{"date":55,"type":20},"2030-07",{"name":57,"class":58},"The Netherlands Cancer Institute","OTHER",6,{"id":61,"slug":4,"hasResults":10,"nctId":62,"briefTitle":63,"officialTitle":64,"acronym":4,"eligibilityCriteria":65,"healthyVolunteers":10,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":66,"targetDuration":4,"studyType":21,"phases":68,"briefSummary":70,"conditions":71,"keywords":73,"overallStatus":74,"whyStopped":4,"lastUpdateSubmitDate":75,"lastUpdatePostDateStruct":76,"startDateStruct":78,"completionDateStruct":80,"leadSponsor":82,"locationsCount":84},"100645254","NCT07680127","TENS of Auricular Vagal Nerve for Radiation Necrosis","Transcutaneous Auricular Vagal Nerve Stimulation for Treatment of Radiation Necrosis","Inclusion Criteria:\n\n* History of glioma or metastatic brain lesion previously treated with whole brain radiation, stereotactic radiation surgery, or fractionated radiation therapy\n* Magnetic resonance imaging (MRI) findings consistent with possible radiation necrosis within 6 weeks prior to enrollment.\n* Candidate for tissue biopsy and Laser Interstitial Thermal Therapy (LITT) ablation of the lesion\n* At least 18 years of age\n* If on corticosteroids, able to discontinue at least 5 days prior to start of transcutaneous auricular vagus nerve stimulation (taVNS) (Arm 1) or sham treatment (Arm 2). A stable physiologic dose of corticosteroids, if used as hormone replacement therapy, may be allowed upon discussion with the investigator. 6. Ability to understand and willingness to sign an institutional review board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.\n\nExclusion Criteria:\n\n* New onset neurologic deficits secondary to radiation necrosis requiring initiation of dexamethasone therapy or other intervention prior to enrollment\n* Currently receiving bevacizumab for treatment of radiation necrosis or has received bevacizumab \\\u003C 6 weeks prior to study enrollment.\n* Currently receiving any investigational agents for treatment of radiation necrosis or has participated in a study of an investigational agent for radiation necrosis within 3 weeks prior to study enrollment.\n* History of cardiac conduction disorders or presence of implanted electronic devices\n* Active Crohn's disease or other inflammatory bowel disease.\n* Pregnant and\u002For breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.",{"count":67,"type":20},40,[69],"NA","This is a multi-center, randomized, blinded trial evaluating the effect of transcutaneous auricular vagal nerve stimulator (taVNS) on radiation necrosis-related cerebral edema. In this study, consenting and eligible patients will be assigned to one of two arms: treatment (Arm 1) or sham (Arm 2). Patients in both arms will have imaging performed and tissue and blood collected for assessment of changes in area of contrast enhancement and cerebral edema, inflammatory markers, and markers of blood-brain barrier permeability.",[26,72],"Cerebral Edema",[26],"NOT_YET_RECRUITING","2026-06-25",{"date":77,"type":51},"2026-07-02",{"date":79,"type":20},"2026-07-31",{"date":81,"type":20},"2029-08-31",{"name":83,"class":58},"Virginia Commonwealth University",1,{"id":86,"slug":4,"hasResults":10,"nctId":87,"briefTitle":88,"officialTitle":88,"acronym":4,"eligibilityCriteria":89,"healthyVolunteers":10,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":90,"targetDuration":4,"studyType":21,"phases":92,"briefSummary":93,"conditions":94,"keywords":97,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":102,"lastUpdatePostDateStruct":103,"startDateStruct":105,"completionDateStruct":107,"leadSponsor":109,"locationsCount":112},"100448857","NCT05124912","REMASTer: REcurrent Brain Metastases After SRS Trial","Inclusion Criteria:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n1. Patients with radiographically proven (by gadolinium-enhanced \\[Gd-\\] MRI) parenchymal brain metastases from histologically confirmed non-central nervous system (CNS) cancer.\n2. Patients with a \"targetable\", bidimensionally-measurable, intracranial lesion that is radiographically recurrent after previous treatment with SRS +\u002F- surgery (craniotomy or LITT). To classify a lesion as radiographically progressive, the lesion must demonstrate a ≥ 25% increase in size following treatment based on the Neuro-Oncology Criteria of Tumor Response for CNS Tumors. To be \"targetable\" for this study, the lesion should be coverable through a planned single LITT trajectory and thus have a maximum perpendicular diameter (perpendicular to the laser trajectory) of 3 cm. An intra-operative decision to utilize two trajectories is acceptable and patient may remain on study.\n3. Patient must be at least 3 months post initial SRS treatment of the target lesion\n4. Target lesion must be amenable to undergo surgical biopsy and LITT treatment as determined by the treating neurosurgeon.\n5. Frozen pathology diagnosis must be attainable.\n6. Patient must be symptomatically stable for a minimum of 3 days prior to the procedure date on a on a max total daily steroid dose equivalent to 4mg of Dexamethasone.\n7. ≥18 years of age\n8. KPS ≥70\n9. Patient is able and willing to complete study requirements\n10. Patients with adequate hematologic parameters (all tests to be performed within \\\u003C4 weeks of biopsy):\n\n    1. ANC ≥ 1.5 X 109\u002FL\n    2. Platelet count ≥ 100 x 109\u002FL\n11. Blood chemistry laboratory value for serum creatinine \\\u003C 1.5 x ULN (test to be performed within \\\u003C4 weeks of biopsy)\n12. Female patients must have a negative serum pregnancy test at screening. (Not applicable to patients with bilateral oophorectomy and\u002For hysterectomy or to those patients who are postmenopausal)\n13. All patients of reproductive potential must agree to use an effective method of contraception during the study\n14. Patients must be accessible for follow-up\n\nExclusion Criteria:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Patients with greater than 3 progressing lesions at time of enrollment. To classify as a radiographically progressive, lesion must demonstrate a ≥ 25% increase in size following treatment based on the RANO criteria. Of note, there is no exclusion for total number of metastases. However, only one lesion can be selected to be the targeted lesion and this lesion alone may be ablated during the study procedure.\n2. Patients with concomitant newly diagnosed intracranial metastases (concurrent with the targetable radiographically progressive lesion), as these will require prioritized and different treatment approaches.\n3. Prior bevacizumab use within 4 weeks of study initiation\n4. Patients with additional concurrent malignancies requiring active treatment, except non-melanoma skin cancer, or in-situ cancer of the cervix\n5. Patients with a serious active infection or other serious underlying medical conditions that would impair the ability of the patient to complete the protocol related QOL questionnaires and cognition assessments\n6. Inability to tolerate or contraindication to steroid therapy (i.e., dexamethasone)\n7. Deemed ineligible or unable to tolerate SRS therapy by treating neurosurgeon and\u002For radiation oncologist\n8. Patients with any condition that would prohibit them from undergoing a surgical procedure, at the discretion of the treating physician team\n9. Patients unwilling or unable to give consent for participation\n10. Patients unable to comply with study requirements\n11. Patients with diffuse leptomeningeal disease\n12. Patients with rapidly progressing extracranial disease",{"count":91,"type":20},261,[69],"Randomized, post-market multi-center study investigating the efficacy of two sets of treatment algorithms in brain metastases (BM) patients at the time of first intervention for radiographic progression after stereotactic radiosurgery (SRS), with or without surgery.",[36,26,95,96],"Recurrent Tumor","Recurrent Metastases",[98,99,100,101,26,36],"Laser Interstitial Thermal Therapy","Stereotactic Radiosurgry","LITT","SRS","2026-06-17",{"date":104,"type":51},"2026-06-18",{"date":106,"type":51},"2022-05-10",{"date":108,"type":20},"2028-10",{"name":110,"class":111},"Monteris Medical","INDUSTRY",9,{"id":114,"slug":4,"hasResults":10,"nctId":115,"briefTitle":116,"officialTitle":117,"acronym":118,"eligibilityCriteria":119,"healthyVolunteers":10,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":120,"targetDuration":4,"studyType":122,"phases":4,"briefSummary":123,"conditions":124,"keywords":126,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":128,"lastUpdatePostDateStruct":129,"startDateStruct":131,"completionDateStruct":133,"leadSponsor":135,"locationsCount":84},"100643397","NCT07632092","Early [18F]-FDG PET Dynamic Analysis in Brain Metastases After Radiotherapy.","Interest of Early Dynamic Analysis of [18F]-FDG PET Images in the Differential Diagnosis Between Recurrence and Radionecrosis in Brain Metastases.","DYNFDGTEP","Inclusion Criteria:\n\n* Patient referred for cerebral \\[18F\\]-FDG PET examination prescribed as part of his usual medical care for brain metastasis.\n* Age ≥ 18 years old\n* Affiliation to a social security program\n* Ability of the subject to understand and express his consent\n\nExclusion Criteria:\n\n* Age under 18 years old\n* Person under guardianship or curatorship\n* Pregnant or breastfeeding woman\n* Primary brain tumors\n* Brain metastases from renal, thyroid or other cancers known to have low avidity for \\[18F\\]-FDG",{"count":121,"type":20},50,"OBSERVATIONAL","Various treatment options are available for brain metastases, depending on factors such as lesion site or number lesions. Radiotherapy is a commonly used treatment. Following stereotactic radiotherapy for brain metastases, a potential complication, namely brain radionecrosis, can occur subsequently. It is essential to differentiate between this radionecrosis and lesion recurrence in order to determine the appropriate treatment approach. Contrast-enhanced magnetic resonance imaging (MRI) is the most widely used technique for monitoring brain metastases. Therefore, patients undergo routine MRI at 3 months and during subsequent follow-ups, but if the lesion evolve and if distinguishing between recurrence and radionecrosis is challenging, an \\[18F\\]-FDG PET scan is then prescribed by oncologists or radiotherapists during follow-up consultations. As part of the standard patient management protocol, a 10-minute image acquisition begins after a 45-60 minutes wait following the radiotracer injection. A second image acquisition is then conducted 3-4 hours later. For both acquisitions, a low-dose X-ray scanner is synchronously coupled to allow attenuation correction of the PET images.\n\nPatient for whom a \\[18F\\]-FDG PET cerebral examination has been prescribed as part of the usual management of brain metastases will be eligible to the protocol. If the patient agrees to participate, an early imaging session is initiated immediately upon radiotracer injection, lasting 15 minutes in addition to the standard acquisition protocol.",[125,36,26],"Short Time Examination",[127,125,36,26],"18F]-FDG PET","2026-06-02",{"date":130,"type":51},"2026-06-08",{"date":132,"type":51},"2026-05-18",{"date":134,"type":20},"2028-11-18",{"name":136,"class":58},"Centre Hospitalier Universitaire, Amiens",{"id":138,"slug":4,"hasResults":10,"nctId":11,"briefTitle":12,"officialTitle":13,"acronym":14,"eligibilityCriteria":139,"healthyVolunteers":10,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":140,"targetDuration":4,"studyType":21,"phases":141,"briefSummary":24,"conditions":142,"keywords":143,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":144,"lastUpdatePostDateStruct":145,"startDateStruct":147,"completionDateStruct":148,"leadSponsor":149,"locationsCount":5},"100584398","Inclusion Criteria:\n\nInclusion all patients (both HGG and BM):\n\n1. Age ≥ 18 years old\n2. First episode of sCRN ≥ 3 months after completion of focal (re-)irradiation, as determined by the local Multidisciplinary Neuro-Oncology Board. A clear working diagnosis of CRN without evidence of a combination with tumour progression is required\n3. KPS score ≤ 90 and a minimum loss of two points in at least one domain of the NANO scale as compared to the maximum score of at that domain due to sCRN\n4. Maximum daily dexamethasone use of 1 mg\u002Fday for the 8 weeks preceding randomization\n\n   1. Dexamethasone may have been prescribed for various indications, except for managing (ongoing) cerebral edema\n   2. Higher doses of dexamethasone are permitted during the week immediately preceding randomization if used specifically for the treatment of sCRN\n5. Able to understand the patient information, online tests and questionnaires\n6. Written informed consent\n\nInclusion BM:\n\n1\\. BM of solid tumour, including all primary tumour types\n\nInclusion HGG:\n\n1\\. A confirmed histological diagnosis of high-grade diffuse glioma according to WHO 2021 criteria, including: astrocytoma, IDH-mutant, grade 3-4; astrocytoma, IDH-wildtype (sybtype molecular glioblastoma); oligodendroglioma, 1p\u002F19q codeleted, grade 3; diffuse glioma, NEC, grade 3-4; or glioblastoma, IDH-wildtype, grade 4\n\nExclusion Criteria:\n\nA potential subject who meets any of the following criteria will be excluded from participation in this study, both for the BM and HGG group:\n\n1. Prior treatment with bevacizumab \\\u003C6 months before diagnosis of sCRN\n2. Life expectancy \\\u003C3 months\n3. Impending radiological or clinical signs of brain herniation necessitating immediate decompressive surgery\n4. Any comorbidity or condition that prevents safe administration of the studied medication, determined by the treating physician, including but not limited to:\n\n   1. Intolerance for murine proteins\n   2. Hypersensitivity or allergy to the active substance or to any of the excipients of bevacizumab or dexamethasone\n   3. Nephrotic syndrome or abnormal renal function\n\n      o Calculated (Cockcroft-Gault) or measured creatinine clearance \\\u003C30 mL\u002Fmin; urine dipstick for proteinuria ≥ 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hours urine collection and must demonstrate ≤ 1 g of protein\u002F24 hr.\n   4. Clinical significant cardiovascular disease\n\n      * Uncontrolled hypertension (systolic BP \\>150mmHg and\u002For diastolic \\>100mmHg) despite the use of ≥ 3 antihypertensive drugs\n      * Previous hypertensive crisis, hypertensive encephalopathy or previous reversible posterior leukoencephalopathy syndrome (RPLS)\n      * Non tumour related vascular event (e.g. cerebral or cardiac ischemia\u002Fbleeding (including transient ischemic attack, cerebral ischemia, unstable angina or angina requiring intervention, myocardial infarction), peripheral arterial thrombus, peripheral artery disease, deep venous thrombosis, lung embolism) \\\u003C 6 months\n      * History of aortic aneurysm or dissection\n      * Congestive heart failure NYHA II-IV\n   5. History of gastro-intestinal fistula, perforation or abscess \\\u003C 6 months\n   6. History of bleeding\n\n      * Relevant pulmonary hemorrhage\u002F hemoptysis \\\u003C 1 month or the presence of a pulmonary lesion with a high risk of bleeding (= central lung tumour and\u002For untreated squamous cell carcinoma) according to the treating physician\n      * Active gastrointestinal bleeding \\\u003C 6 months\n      * Evidence of recent intracranial hemorrhage on MRI brain \\\u003C3 months. Asymptomatic presence of hemosiderin depositions or punctate hemorrhage in the tumour do not serve as a ground for exclusion\n   7. Excess risk of bleeding\n\n      * History or evidence of inherited bleeding diathesis or significant coagulopathy with the risk of bleeding\n      * Decreased platelet count \\\u003C 75x109\u002FL\n   8. Risk of wound healing complications\n\n      * Significant non-healing wound, (peptic) ulcer or bone fracture\n      * Major surgical procedure (including open biopsy) or significant traumatic injury within 28 days prior to first study treatment or planned surgical procedure within the following next 28 days after planned study inclusion\n      * Minor surgical procedure, stereotactic\u002Fcore biopsy, fine needle aspiration within 7 days prior to first study treatment\n   9. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hours urine collection and must demonstrate ≤ 1 g of protein\u002F24 hr.\n   10. Previous, current or planned high dose radiotherapy in the abdomen\n   11. Pregnancy or lactation. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of HCG) within 7 days prior to randomization. WOCBP and female partners of male patients must comply with adequate contraception methods as requested by the study protocol\n   12. Evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the study treatment, affect patient compliance or place the patient at high risk for treatment-related complications according to the treating physician\n   13. Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another interventional study In case of uncertainty, consult the principal investigator of the study site.",{"count":19,"type":20},[23],[26,27,28,29,30,31,32],[34,35,36,37,38,39,40,41,42,43,44,45,46],"2026-02-24",{"date":146,"type":51},"2026-02-25",{"date":53,"type":51},{"date":55,"type":20},{"name":57,"class":58},""]