[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"mgmt-unmethylated-glioblastoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:mgmt-unmethylated-glioblastoma":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,6,0,[8,40,70,98,120,144],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":4},"100627732","phase-3-temporally-modulated-pulsed-radiation-therapy-versus-standard-radiation-therapy-for-the-treatment-of-newly-diagnosed-idh-wildtype-mgmt-unmethylated-glioblastoma-100627732",false,"NCT07452458","Temporally-Modulated Pulsed Radiation Therapy Versus Standard Radiation Therapy for the Treatment of Newly Diagnosed, IDH Wildtype, MGMT-Unmethylated Glioblastoma","A Randomized Phase III Study Comparing Temporally-Modulated Pulsed Radiation Therapy (TMPRT) Versus Standard Radiation Therapy With Temozolomide for Adults With Newly Diagnosed MGMT-Unmethylated Glioblastoma","Inclusion Criteria:\n\n* PRIOR TO STEP 1 REGISTRATION:\n* No known IDH mutation. (If tested before step 1 registration, patients known to have IDH mutation in the tumor on local or other testing are ineligible and should not be registered).\n* Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block and hematoxylin and eosin (H\\&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Surgical resection is required; stereotactic biopsy alone is not allowed because it will not provide sufficient tissue for MGMT analysis. Note that tissue for central pathology review and central MGMT assessment must be shipped to the New York University (NYU) Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 30. If tissue cannot be shipped by postoperative calendar day 30, then patients may NOT enroll on this trial as central pathology review will not be complete in time for the patient to start treatment no later than 8 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be completed within 10 business days of receipt of tissue. Results will be entered by the central lab directly into Rave. Note: In the event of an additional tumor resection(s), tissue must be shipped within 30 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection.\n* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to Step 1 registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.\n* No known leptomeningeal disease or metastatic disease outside the brain.\n* Age ≥ 18\n* Because neurocognitive testing is the primary goal of this study, patients must be proficient in English or French Canadian.\n* Karnofsky Performance Status ≥ 70\n* Hemoglobin ≥ 10 g\u002Fdl (Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) ≥ 10.0 g\u002Fdl is acceptable)\n* Leukocytes ≥ 2,000\u002Fmm\\^3 OR absolute neutrophil count ≥ 1,500\u002Fmm\\^3\n* Platelets ≥ 100,000\u002Fmm\\^3\n* Creatinine clearance (CrCl) ≥ 50 mL\u002Fmin\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase \\[SGPT\\]) ≤ 3 x ULN\n* No prior cranial radiation therapy that would result in overlap of radiation therapy fields.\n* No previous therapy for GBM except surgery, laser interstitial thermal therapy (LITT) or Gliadel wafer.\n\n  * Note: 5-aminolevulinic acid (ALA)-mediated fluorescence-guided resection (FGR) photodynamic therapy (PDT) or fluorescein administered prior to\u002Fduring surgery to aid resection is not exclusionary and is not considered a chemotherapy or intracerebral agent.\n* No history of unstable angina requiring hospitalization in the last 3 months\n* No history of myocardial infarction within the last 3 months\n* New York Heart Association Functional Classification II or better (NYHA Functional Classification III\u002FIV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)\n* No active infection currently requiring IV antibiotic management\n* No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy\n* No movement disorder that could impede ability to lie still with an immobilization mask for approximately 40 minutes\n* No significant sensory deficits (i.e., blindness, mutism) that would prohibit participation of NCF testing\n* No history of allergic reaction attributed to compounds of similar chemical or biological composition to temozolomide\n* PRIOR TO STEP 2 REGISTRATION:\n* The following baseline neurocognitive tests must be completed within 28 days prior to Step 2 registration: (Hopkins Verbal Learning Test - Revised \\[HVLT-R\\], Trail Making Test \\[TMT\\], Controlled Oral Word Association \\[COWA\\]). The neurocognitive tests will be uploaded into RAVE for evaluation by Dr. Wefel. The following scores must be obtained for patient eligibility: HVLT-R Total Recall \\> 5, HVLT-R Delayed Recall \\> 3, HVLT-R Delayed Recognition \\> -10, TMT Part A . 2738, TMT Part B . 3724, COWA . 12. Central review of the Neurocognitive tests will be completed in Rave within 3 business days after the upload is completed. Users with the Rave clinical research associate (CRA) role will be able to view the results in Rave. The CRA must confirm that the results are available and meet eligibility requirements prior to proceeding with Step 2 Registration.\n\n  * NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.\n  * Note: Patients whose neurocognitive test scores do not meet the criteria above will not be eligible for the study and will be reported as ineligible due to \"Failure to meet Neurocognitive testing criteria\" on Step 2 registration.\n* Pathology proven diagnosis of IDH-wildtype glioblastoma with unmethylated MGMT promoter confirmed by central pathology review. IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e. IDH-wildtype). (If a mutation is identified then the patient will be ineligible and must be registered as ineligible at Step 2.)\n\n  * Central pathology review will generally be completed within 10 business days of receipt of the tissue. Users with the Rave CRA role will be able to view the results in Rave. It must be confirmed that the results are available and meet eligibility requirements prior to proceeding with Step 2 Registration.\n  * Note: Patients with tissue that is insufficient or inadequate for analysis, has failed MGMT testing, or has indeterminate or methylated MGMT promoter are excluded and will be reported as a \"central pathology review failure\" on step 2 registration.","ALL","18 Years",{"count":19,"type":20},398,"ESTIMATED","INTERVENTIONAL",[23],"PHASE3","This phase III trial compares temporally-modulated pulsed radiation therapy versus standard radiation therapy in treating patients with newly diagnosed, IDH wildtype, MGMT-unmethylated glioblastoma. After completion of surgery, the standard of care for glioblastoma is radiation therapy. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. For older and frail patients, standard treatment also includes the chemotherapy drug temozolomide. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Approximately 70% of glioblastoma patients have MGMT-unmethylated status. MGMT unmethylated tumors are less likely to respond to temozolomide chemotherapy, so there is more reliance on radiation therapy to kill the tumor cells. Recent clinical trials studying new therapies for MGMT-unmethylated glioblastoma have failed to improve outcomes over temozolomide. These recent studies also indicate that 80% of patients experience a decline in memory and thinking function after treatment. TMPRT differs from standard radiation therapy by delivering the same amount of radiation dose in 10-13 \"pulses\" with 3-minute breaks between pulses. TMPRT with temozolomide may work better than standard radiation therapy with temozolomide in increasing survival, as well as improving memory and thinking function in patients with newly diagnosed, IDH wildtype, MGMT-unmethylated glioblastoma.",[26,27],"Glioblastoma, IDH-Wildtype","MGMT-Unmethylated Glioblastoma","NOT_YET_RECRUITING","2026-04-28",{"date":31,"type":32},"2026-05-04","ACTUAL",{"date":34,"type":20},"2026-06-08",{"date":36,"type":20},"2031-07-15",{"name":38,"class":39},"NRG Oncology","OTHER",{"id":41,"slug":42,"hasResults":11,"nctId":43,"briefTitle":44,"officialTitle":45,"acronym":4,"eligibilityCriteria":46,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":47,"targetDuration":4,"studyType":21,"phases":49,"briefSummary":51,"conditions":52,"keywords":56,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":60,"lastUpdatePostDateStruct":61,"startDateStruct":63,"completionDateStruct":65,"leadSponsor":67,"locationsCount":69},"100530409","phase-1-anti-egfrviii-synnotch-receptor-induced-anti-epha2il-13ralpha2-car-e-sync-t-cells-100530409","NCT06186401","Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2\u002FIL-13Ralpha2 CAR (E-SYNC) T Cells","Phase 1 Study of Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2\u002FIL-13R alpha2 CAR (E-SYNC) T Cells in Adult Participants With EGFRvIII+ Glioblastoma","Inclusion Criteria:\n\n* Inclusion Criteria for Cohort 1:\n\n  1. Age \\>= 18 years.\n  2. Karnofsky performance status (KPS) score of \\>=70.\n  3. All participants must have adequate organ function defined as:\n\n     1. Peripheral absolute neutrophil count \\>=1000\u002Fmm\\^3.\n     2. Platelet count \\>=100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n     3. Absolute lymphocyte count (ALC) \\>= 300\u002FμL and\u002For Cluster of differentiation 3 (CD3) count of \\>=150\u002FμL.\n     4. Creatinine clearance or radioisotope glomerular filtration rate \\>= 50 mL\u002Fmin\u002F1.73m\\^2.\n     5. Total Bilirubin \\\u003C= 1.5 x ULN except for Gilbert's syndrome and\n     6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C= 3x upper limit of normal (ULN).\n     7. Left ventricular ejection fraction (LVEF) \\>= 50% by echocardiogram or multi-gated acquisition scanning (MUGA).\n     8. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \\> 92% while breathing room air.\n  4. Pathological criteria: EGFRvIII+ GBM from most recent surgery, confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using a next-generation sequencing panel.\n  5. MGMT promoter must be unmethylated or with a methylation index \\\u003C 3.\n  6. Must have completed at least standard of care (SOC) external beam radiotherapy (EBRT) as initial therapy.\n  7. Participants must be anticipated to be able to complete E-SYNC T cell infusion within 12 weeks after completion of EBRT.\n  8. All participants must be off systemic steroids for 3 days or more prior to leukapheresis.\n  9. Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed) and for study treatment.\n\nNOTE: There are two sets of eligibility criteria for Cohort 2. Step 1 defines eligibility for tissue screening and apheresis, and Step 2 defines eligibility for study enrollment and E-SYNC T cell treatment.\n\n* Inclusion Criteria for Cohort 2, Step 1:\n\n  1. Age \\>=18 years.\n  2. KPS score \\>=70.\n  3. All participants must have adequate organ function defined as:\n\n     1. Peripheral absolute neutrophil count \\>=1000\u002Fmm\\^3.\n     2. Platelet count \\>=100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n     3. Absolute lymphocyte count (ALC) \\>= 300\u002FμL and\u002For CD3 count of \\>=150\u002FμL.\n     4. Creatinine clearance or radioisotope glomerular filtration rate \\>= 50 mL\u002Fmin\u002F1.73m\\^2.\n     5. Total Bilirubin \\\u003C= 1.5 x ULN except for Gilbert's syndrome and\n     6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C= 3x upper limit of normal (ULN).\n     7. Left ventricular ejection fraction (LVEF) \\>= 50% by echocardiogram or multi-gated acquisition scanning (MUGA).\n     8. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \\> 92% while breathing room air.\n  4. Pathological criteria: EGFRvIII+ GBM from most recent surgery, as defined by an EGFRvIII + H-score of \\>=250 based on central review.\n  5. All participants must be off systemic steroids for 3 days or more prior to leukapheresis.\n  6. Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed).\n* Inclusion Criteria for Cohort 2, Step 2. Note: Prior to Step 2, participants must have undergone leukapheresis in Step 1. In addition:\n\n  1. KPS score \\>=70.\n  2. Must have received at least SOC EBRT as initial therapy; any number of prior recurrences is allowed.\n  3. Pathological criteria: EGFRvIII+ GBM from most recent surgery, as defined by an EGFRvIII + H-score of \\>=250 based on central review.\n  4. Must have radiographic progression consistent with the Response assessment in neuro-oncology criteria (RANO) criteria for progressive disease (PD)\n  5. Recurrence must be surgically amenable, with expectation for ability to resect at least 500mg of tumor tissue\n  6. Participants with reproductive potential agree to use reliable and double barrier method of contraception during the study and for at least 6 months after the last study intervention, including refraining from donating sperm during this period.\n  7. Females of childbearing potential must have a negative serum beta-Human Chorionic Gonadotropin (hCG) pregnancy test prior to receiving study interventions.\n  8. All participants must have adequate organ function defined as:\n\n     1. Peripheral absolute neutrophil count \\>=1000\u002Fmm\\^3.\n     2. Platelet count \\>=100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n     3. Absolute lymphocyte count (ALC) \\>= 300\u002FμL and\u002For CD3 count of \\>=150\u002FμL.\n     4. Creatinine clearance or radioisotope glomerular filtration rate \\>= 50 mL\u002Fmin\u002F1.73m\\^2.\n     5. Total Bilirubin \\\u003C= 1.5 x ULN except for Gilbert's syndrome and\n     6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C= 3x upper limit of normal (ULN).\n     7. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) have to be within normal limits, unless the participant has been therapeutically anticoagulated for previous venous thrombosis.\n     8. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \\> 92% while breathing room air.\n     9. Adequate cardiac function, confirmed within the last 12 months, defined as left ventricular ejection fraction (LVEF) \\>= 40% by echocardiogram or multi-gated acquisition scanning (MUGA).\n  9. Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed).\n\nExclusion Criteria:\n\n* Exclusion Criteria for Cohort 1\n\n  1. Participant who has been treated with any investigational agents and chemotherapy targeting GBM \\\u003C= 4 weeks prior to date of study registration. Exceptions to this include: must be \\>=23 days from last dose of temozolomide (TMZ) or radiotherapy, mush be \\>= 6 weeks from last dose of nitrosourea.\n  2. Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of eligibility confirmation.\n  3. Known addiction to alcohol or illicit drugs.\n  4. Prior treatment with any Epithelial Growth Factor Receptor (EGFR)-targeting therapy.\n  5. Participants with leptomeningeal dissemination.\n  6. Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy. Participants who are currently using non-systemic steroids (e.g., inhaled, intranasal, ocular, topical) are not excluded from the study.\n  7. Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.\n  8. Participants who have received prior solid organ or bone marrow transplantation.\n  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, second cancer currently receiving active treatment or anticipated to receive treatment within the next year, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n  10. Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.\n* Exclusion Criteria for Step 1 for Cohort 2\n\n  1. Participant who has been treated with any investigational agents or chemotherapy targeting GBM \\\u003C=4 weeks prior to date of study registration. Exceptions to this include: must be\\>= 23 days from last dose of TMZ or radiotherapy, must be\\>=6 weeks from last dose of nitrosourea.\n  2. Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of Step 1 eligibility confirmation.\n  3. Uncontrolled active infection.\n  4. Participants with a known disorder that affects their immune system, such as HIV or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy.\n\n     Participants who are currently using non-systemic steroids (e.g., inhaled, intranasal, ocular, topical) are not excluded from the study.\n  5. Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.\n  6. Known addiction to alcohol or illicit drugs.\n* Exclusion Criteria for Step 2 for Cohort 2\n\nPrior to Step 2, participants must have undergone leukapheresis in Step 1. In addition:\n\n1. Prior treatment with any EGFR-targeting therapy\n2. Participant who has been treated with any investigational agents or chemotherapy targeting GBM \\\u003C= 4 weeks prior to date of study registration. Exceptions to this include: must be \\>= 23 days from last dose of TMZ or radiotherapy, must be \\>= 6 weeks from last dose of nitrosourea.\n3. Participants with imaging or clinical evidence of uncontrolled tumor mass effect; the assessment of mass effect will be made by the Investigators.\n4. Participants with leptomeningeal dissemination.\n5. Participants with a known disorder that affects their immune system, such as HIV or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy.\n\n   Participants who are currently using inhaled, intranasal, ocular, topical, or other non-oral or non-IV steroids are not necessarily excluded from the study.\n6. Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.\n7. Participants who have received prior solid organ or bone marrow transplantation.\n8. Female participants who are pregnant or breast-feeding.\n9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, second cancer currently receiving active treatment or anticipated to receive treatment within the next year, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n10. Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.",{"count":48,"type":20},20,[50],"PHASE1","This phase I trial tests the safety, side effects, and best dose of E-SYNC chimeric antigen receptor (CAR) T cells after lymphodepleting chemotherapy in treating patients with EGFRvIII positive (+) glioblastoma. Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so the CAR T cells will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine before treatment with CAR T cells may make the CAR T cells more effective.",[53,54,27,55],"EGFR Gene Mutation","Glioblastoma","Recurrent Glioblastoma",[57,58],"Immunotherapy","CAR T Therapy","RECRUITING","2026-03-12",{"date":62,"type":32},"2026-03-16",{"date":64,"type":32},"2024-04-30",{"date":66,"type":20},"2027-12-31",{"name":68,"class":39},"Hideho Okada, MD, PhD",1,{"id":71,"slug":72,"hasResults":11,"nctId":73,"briefTitle":74,"officialTitle":75,"acronym":4,"eligibilityCriteria":76,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":77,"targetDuration":4,"studyType":21,"phases":79,"briefSummary":81,"conditions":82,"keywords":85,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":88,"lastUpdatePostDateStruct":89,"startDateStruct":91,"completionDateStruct":93,"leadSponsor":95,"locationsCount":97},"100554845","phase-1-db107-rrv-db107-fc-and-radiation-therapy-with-or-without-temozolomide-tmz-for-high-grade-glioma-100554845","NCT06504381","DB107-RRV, DB107-FC, and Radiation Therapy With or Without Temozolomide (TMZ) for High Grade Glioma","A Phase I\u002FIIa Study to Evaluate the Efficacy of DB107-RRV (Formerly Toca511), Administered to Subjects at Time of Resection and Intravenously Thereafter, in Combination With DB107-FC (Formerly Toca FC) and Radiation Therapy or DB107-FC, Temozolomide (TMZ) and Radiation Therapy in Patients With Newly Diagnosed High Grade Glioma","Inclusion Criteria:\n\nEach patient must meet all of the following inclusion criteria to be eligible for study entry:\n\n1. Participant has provided written informed consent.\n2. Participant is between 18 years of age and 75 years of age, inclusive.\n3. Participant must have a Karnofsky Performance Scale (KPS) of \\>= 70.\n4. Participant must have newly diagnosed adult-type diffuse gliomas (World Health Organization Classification 2021) that has not been previously treated with surgery, radiation or chemotherapy (specifically astrocytoma, Isocitrate dehydrogenase (IDH)-mutant or glioblastoma, IDH-wildtype).\n5. Based on the pre-operative evaluation by neurosurgeon, participant is a candidate for \\>= 80% resection of the enhancing region.\n6. The primary tumor must be made available for central testing for IDH1 mutation, O6-methylguanine-DNA methyl-transferase (MGMT) methylation status.\n7. Willing to provide a blood sample to determine Denovo Genomic Marker 7 (DGM7) status.\n8. Laboratory values adequate for patient to undergo surgery, including:\n\n   1. Platelet count \\>= 60,000\u002Fmm\\^3\n   2. Hemoglobin \\>= 10 g\u002FdL\n   3. Absolute neutrophil count (ANC) \\>= 1,500\u002Fmm\\^3\n   4. Absolute lymphocyte count \\>= 500\u002Fmm\\^3\n   5. Total bilirubin \\\u003C=1.5 x upper limit of normal (ULN) (unless patient had Gilbert's syndrome)\n   6. alanine aminotransferase (ALT) \\\u003C= 2.5 x ULN\n   7. Estimated glomerular filtration rate of at least 50 mL\u002Fmin by Cockcroft Gault Formula\n9. Female participants of child-bearing potential and male participants must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30-days prior to the first administration of study drug, for the duration of study participation, and for 90-days following completion of the therapy. Should a female participant become pregnant or suspect a pregnancy while participating in this study, the treating physician must be informed immediately. IF a male participant impregnates or is suspected of impregnating a woman while participating in this study, the treating physician must be informed immediately.\n\n   • A female of child-bearing potential is any women (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:\n   * Has not undergone a hysterectomy or bilateral oophorectomy or\n   * Has not had \\>= 12 months of non-therapy-induced amenorrhea.\n10. Participants must not be breastfeeding.\n11. Participants must have the ability to understand, and the willingness to comply with the scheduled visits, treatment schedule, laboratory testing and other requirements of the study.\n\nExclusion Criteria:\n\nParticipants may not meet any of the following exclusion criteria to be eligible for study entry:\n\n1. Prior treatment for High Grade Glioma (HGG).\n2. History of other malignancy unless the participant has been disease-free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is not exclusionary regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment.\n3. Histological confirmed oligodendroglioma (IDH-mutant and 1p.19q-codeleted) or mixed glioma.\n4. A contrast-enhancing brain tumor that is any of the following:\n\n   1. Multi-focal (defined as 2 separate areas of presumed tumor whether contrast enhancing or not, measuring at least 1cm in 2 planes that are not contiguous\n   2. Associated with either diffuse subependymal or leptomeningeal dissemination or\n   3. \\> 5cm in any dimension.\n5. Participant has or had an active infection requiring antibiotic, antifungal or antiviral therapy in the 4 weeks preceding study Cycle 1: Day 1.\n6. Participant has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be interrupted for surgery.\n7. Participant is HIV positive.\n8. Participant has Hepatitis B (positive test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and positive test for hepatitis B Virus (HBV) DNA) or Hepatitis C (positive tests for hepatitis C Virus (HCV) Antibody and HCV-RNA) or Hepatitis B and C co-infection (positive test for HBsAg or HBcAb and positive test for HCV Antibody).\n9. Participant has a history of allergy or intolerance to flucytosine (DB107-FC).\n10. Participant has a gastrointestinal disease that would, in the opinion of the Investigator, prevent him or her from being able to swallow or absorb flucytosine.\n11. Participant intends to undergo treatment with the Gliadel® wafer at the time of resection surgery or has received Gliadel® wafer \\\u003C 30 days from Cycle 1: Day 1.\n12. Severe pulmonary, cardiac or other systemic disease, which as per Investigator assessment would prevent surgical resection.\n13. Participant who have any other disease or condition, which as per Investigator assessment may affect the participant's compliance or place the participant at higher risk of potential treatment complications.",{"count":78,"type":20},70,[50,80],"PHASE2","This is a multicenter, open-label study of DB107-RRV (formerly Toca 511) and DB107-FC (formerly Toca FC) when administered following surgical resection in newly diagnosed High Grade Glioma (HGG) patients. The study is designed to evaluate whether treatment with DB107-RRV in combination with DB107-FC when added to standard of care provides clinical benefit to newly diagnosed HGG when compared to historical performance previously determined in well controlled clinical trials published in the peer reviewed literature. This study is going to be conducted in newly diagnosed HGG patients receiving with maximum surgical resection treatment followed by radiation and temozolomide treatment using the established Stupp Protocol for O6-methylguanine-DNA methyl-transferase (MGMT) methylated patients or radiation therapy for MGMT unmethylated patients.",[83,27,84],"High Grade Glioma","MGMT-Methylated Glioblastoma",[86,87],"Gene therapy","Combination therapy","2026-03-09",{"date":90,"type":32},"2026-03-11",{"date":92,"type":32},"2025-01-08",{"date":94,"type":20},"2042-01-31",{"name":96,"class":39},"University of California, San Francisco",5,{"id":99,"slug":100,"hasResults":11,"nctId":101,"briefTitle":102,"officialTitle":103,"acronym":4,"eligibilityCriteria":104,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":105,"targetDuration":4,"studyType":21,"phases":107,"briefSummary":108,"conditions":109,"keywords":4,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":110,"lastUpdatePostDateStruct":111,"startDateStruct":113,"completionDateStruct":115,"leadSponsor":117,"locationsCount":119},"100506812","phase-2-wp1066-and-radiation-therapy-in-treating-patients-with-newly-diagnosed-glioblastoma-100506812","NCT05879250","WP1066 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma","A Multi-Arm, Open Label, Phase II Trial of WP1066 and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma","Inclusion Criteria:\n\n* Newly diagnosed, histologically confirmed World Health Organization (WHO) glioblastoma multiforme (GBM), IDH wild-type\n\n  * External pathology reports are permitted for confirmation of histological diagnosis\n  * Documentation of isocitrate dehydrogenase (IDH) wild-type status will be by IDH1 R123H immunohistochemistry, except for patients =\\\u003C age 54 for whom IDH sequencing will be required to detect noncanonical IDH mutations\n* Documentation of O6-methylguanine-DNA methyltransferase (MGMT) unmethylated status per testing at any Clinical Laboratory Improvement Amendment (CLIA) certified laboratory\n* Cohort 1 only: Patients with prior gross total resection (GTR)\n* Cohort 2 only: Patients without prior gross total resection (GTR)\n* Cohort 2 only: Measurable disease in the brain (per RANO criteria) on brain magnetic resonance imaging (MRI) scan conducted within =\\\u003C 4 weeks prior to initiating trial therapy\n* Cohort 2 only: Patients who would benefit from non-emergent, palliative surgical resection, in the opinion of the local site's tumor board\n* Able to initiate trial therapy within 8 weeks of the initial brain surgical procedure (biopsy or resection) that lead to the patient's initial diagnosis of GBM\n* Age \\>=18 years\n* Karnofsky performance scale score \\>= 60%\n* White blood cell (WBC) count \\>= 3.0 x 10\\^9\u002FL (within =\\\u003C 30 days prior to registration) (without growth factor support and\u002For receipt of blood products within =\\\u003C 14 days prior to testing)\n* Absolute neutrophil count (ANC) \\>= 1.0 x 10\\^9\u002FL (within =\\\u003C 30 days prior to registration) (without growth factor support and\u002For receipt of blood products within =\\\u003C 14 days prior to testing)\n* Platelet count \\>= 75 x 10\\^9\u002FL (within =\\\u003C 30 days prior to registration) (without growth factor support and\u002For receipt of blood products within =\\\u003C 14 days prior to testing)\n* Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN) or direct bilirubin =\\\u003C ULN for subjects with total bilirubin levels \\> 1.5 x ULN (within =\\\u003C 30 days prior to registration)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) =\\\u003C 2.5 x ULN (within =\\\u003C 30 days prior to registration)\n* Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x ULN (within =\\\u003C 30 days prior to registration)\n* Creatinine or creatinine clearance within normal institutional limits. A creatinine level above the institutional normal limit is acceptable, provided creatinine clearance (CrCl) is \\>= 60 mL\u002Fmin\u002F1.73 m\\^2 (within =\\\u003C 30 days prior to registration). Creatinine clearance should be calculated using the Cockcroft-Gault formula\n* International normalized ratio (INR) =\\\u003C 1.5 x ULN or for subjects receiving anticoagulant therapy, INR must be within the therapeutic range of intended use of anticoagulants, as determined by the treating investigator (within =\\\u003C 30 days prior to registration)\n* Activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN or for subjects receiving anticoagulant therapy, aPTT must be within the therapeutic range of intended use of anticoagulants, as determined by the treating investigator (within =\\\u003C 30 days prior to registration)\n* Willing and able to tolerate brain MRI with contrast. Patients with any known severe allergy to contrast agent(s) should not participate in the study. Patients with mild allergies to contrast agents (e.g., rash only) may participate in the study per treating investigator discretion; it is recommended that these patients be pretreated with acetaminophen and diphenhydramine \\[or other institutional standard combination of agent(s) for allergy prep\\] prior to injection of the contrast agent\n* Willing and able to follow the below contraception requirements:\n\nFor Females:\n\n* Female subjects of childbearing potential (defined below) must agree to use adequate contraception (e.g., abstinence or 2 methods of birth control, such as a barrier method in combination with hormonal contraception) starting from the time of informed consent, throughout the duration of treatment with WP1066, and for 2 months after the last dose of WP1066. They also must agree to not donate\u002Ffreeze eggs during the same timeframe. A female of reproductive potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets both of the following two criteria:\n\n  * Has not undergone a hysterectomy or bilateral oophorectomy\n  * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \\> 12 months)\n\nFor Males:\n\n* Male subjects must agree to use adequate contraception (e.g., abstinence or 2 methods of birth control, such as a barrier method in combination with partner's use of hormonal contraception) starting from the time of informed consent, throughout the duration of treatment with WP1066, and for 4 months after the last dose of WP1066. They also must agree to not donate sperm during the same timeframe Note: The effects of WP1066 on the developing human fetus are unknown. WP1066 could potentially be teratogenic or have abortifacient effects. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately\n\n  * Subject (or subject's legally authorized representative if subject has impaired decision-making capacity) must have the ability to understand and the willingness to sign a written informed consent document\n  * Both men and women of all races and ethnic groups may participate in this trial\n\nExclusion Criteria:\n\n* Receipt of investigational agents within =\\\u003C 2 weeks prior to registration\n* Prior receipt of gene therapy, at any time\n* Prior receipt of bevacizumab, at any time\n* Prior receipt of Gliadel, at any time\n* Patients who are on active therapy with Optune and who are unable to safely discontinue Optune prior to initiating trial therapy Note: Patients who can safely discontinue Optune prior to initiating trial therapy may participate\n* Patients who are on active therapeutic anti-cancer therapy and who are unable to discontinue the anti-cancer therapy prior to initiating trial therapy Note: Patients who discontinue anti-cancer therapy prior to initiating trial therapy may participate. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial may participate\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to WP1066 or its excipients\n* Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy Note: These patients are ineligible because of the potential for pharmacokinetic interactions with WP1066. (HIV testing is not required, unless mandated by a local health authority.)\n* Patients who have received drugs that significantly interact with CYP450 enzyme(s) within =\\\u003C 2 weeks prior to planned first study treatment day Note: Patients who are able to safely discontinue the aforementioned agents \\> 2 weeks prior to initiating treatment with WP1066 may participate. The enzymatic metabolism profile of WP1066 is unknown. Drugs that have a minor interaction with CYP450 are allowed, and drugs with a moderate interaction are allowed at the principal investigators (PI's) discretion. Zofran (ondansetron) is allowed\n* Patients who have received any of the following agents within 7 days of planned first study treatment day:\n\n  * Agents that are predominantly CYP2D6, 2C9, or 2C19 substrates\n  * Agents that are strong inhibitors or inducers of CYP2D6, 2C9, or 2C19\n  * Agents that are sensitive substrates of CYP3A4 with narrow therapeutic range Note: Patients who are able to safely discontinue the aforementioned agents \\> 7 days prior to initiating treatment with WP1066 may participate. The enzymatic metabolism profile of WP1066 is unknown. Drugs that are minor CYP2D6, 2C9 or 2C19 substrates; minor inhibitors or inducers of CYP2D6, 2C9, or 2C19; or minor substrates of CYP3A4 are allowed. Moderate drugs will be allowed per PI's discretion. Zofran (ondansetron) is allowed\n* Patients on corticosteroids who require escalation of the corticosteroid dose Note: Patients receiving a stable or decreasing dose for at least one week may participate. Zofran (ondansetron) is allowed\n* History of brain hemorrhage, unless the following exception is met:\n\n  * Exception: Small, asymptomatic brain hemorrhage may be permitted, provided written documentation of PI approval has been obtained Note: The potential for further hemorrhaging with the use of WP1066 is unknown. It will be at the PIs discretion to enroll a patient who has a small, asymptomatic brain hemorrhage, but patients who have had symptomatic hemorrhages will be excluded\n* Uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drug\n* Lesion(s) larger than 50 mm in maximal diameter on MRI, or with midline shift exceeding 5 mm, or with hydrocephalus\n* Diffuse leptomeningeal disease Note: Because one of the objectives is PFS based on radiographic volumetric analysis of the tumor, the presence of diffuse leptomeningeal disease is excluded. This is secondary to the inadequacy of measuring the extent of the tumor burden within this setting and the very poor prognosis of these patients\n* Corrected QT (QTc) B interval \\>= 450 ms These patients are excluded because the cardiac toxicities of WP1066 are unknown. Concomitant use of agents that prolong the QT interval should be avoided whenever feasible, or used with caution. Zofran (ondansetron) is allowed\n* Subjects who are at increased risk for radiation therapy (RT)-associated toxicities, such as those with known active collagen vascular disease (e.g., scleroderma, Sjogren's disease, etc.) or other inherited RT-hypersensitivity syndromes (e.g., Gorlin syndrome, Fanconi anemia, ataxia-telangiectasia, etc.)\n* For female patients of childbearing potential only:\n\nPatients with a positive serum beta-human chorionic gonadotropin (HCG) pregnancy test within =\\\u003C 2 days prior to planned start date for trial therapy or who are immediately planning to become pregnant\n\n* Breastfeeding patients who are unwilling\u002Funable to discontinue breastfeeding while receiving WP1066 Note: Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with WP1066, breastfeeding should be discontinued if the mother is treated with WP1066. Patients who discontinue breastfeeding prior to initiating treatment with WP1066 may participate\n* Uncontrolled intercurrent illness or condition including, but not limited to any of the following:\n\nOngoing or active infection requiring systemic treatment, except uncomplicated urinary tract infection;\n\n* Symptomatic congestive heart failure\n* Unstable angina pectoris\n* Cardiac arrhythmia\n* Psychiatric illness\u002Fsocial situation that would limit compliance with study requirements\n* Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the subject's safety or study endpoints",{"count":106,"type":20},39,[80],"This phase II trial tests how well the combination of WP1066 and radiation therapy works in treating newly diagnosed glioblastoma. Glioblastoma is difficult to treat effectively because the cells within the tumor vary widely and are controlled by factors within and around the tumor, requiring multiple approaches to treat the tumor. The study drug WP1066 targets a specific pathway, known as STAT3, which is responsible for promoting tumor growth and causing the body's immune system to avoid attacking the tumor. Radiation therapy prevents glioblastoma from growing. Giving WP1066 with radiation therapy may prevent glioblastoma from growing and prolong survival.",[26,27],"2025-12-26",{"date":112,"type":32},"2025-12-30",{"date":114,"type":32},"2024-05-22",{"date":116,"type":20},"2028-12-27",{"name":118,"class":39},"Northwestern University",2,{"id":121,"slug":122,"hasResults":11,"nctId":123,"briefTitle":124,"officialTitle":125,"acronym":4,"eligibilityCriteria":126,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":127,"targetDuration":4,"studyType":21,"phases":129,"briefSummary":130,"conditions":131,"keywords":4,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":136,"lastUpdatePostDateStruct":137,"startDateStruct":138,"completionDateStruct":140,"leadSponsor":142,"locationsCount":69},"100592259","phase-2-ruxolitinib-with-radiation-and-temozolomide-compared-to-radiation-and-temozolomide-for-newly-diagnosed-glioblastoma-100592259","NCT06991101","Ruxolitinib With Radiation and Temozolomide Compared to Radiation and Temozolomide for Newly Diagnosed Glioblastoma","Randomized Phase 2 Trial of Ruxolitinib in Combination With Radiation and Temozolomide Compared to Radiation and Temozolomide for Newly Diagnosed Glioblastoma.","Inclusion Criteria:\n\n1. Provision of signed informed consent form.\n2. Stated willingness to comply with all study procedures and availability for the duration of the study.\n3. Individuals of any sex, gender, race, or ethnicity ≥ 18 years of age.\n4. Histologically confirmed glioblastoma as defined by the World Health Organization (WHO) 2021 Criteria (IDH-wildtype) that is either methylated, unmethylated, or indeterminate MGMT.\n5. Confirmation that patient has sufficient tissue to undergo MGMT and IDH testing, as mandated.\n6. Must have a Karnofsky performance status (KPS) ≥ 70% (i.e., the patient must be able to care for themself with occasional help from others).\n7. Adequate organ (liver and renal) and bone marrow function within 14 days before randomization. For all parameters listed below, the most recent results available must be used:\n\n   1. Absolute neutrophil count (ANC) ≥ 1500\u002Fmm3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment.\n   2. Platelet count ≥ 100,000\u002Fmm3. Note: Platelet transfusion is not allowed within 1 week prior to registration.\n   3. Total bilirubin (TBL) ≤ 1.5 × institutional upper limit of normal (ULN).\n   4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.\n   5. Serum albumin ≥ 2.5 g\u002FdL.\n8. Patients able to become pregnant: use of highly effective contraception for at least one (1) month prior to screening and agreement to use such a method. Should a participant become pregnant or suspect that they are pregnant while participating in this study, they should notify the treating physician immediately. Such individuals must have a negative pregnancy test.\n9. Patients must have no concurrent malignancy except curatively treated early-stage bladder and prostate cancer that has been completed resected, basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Patients with other prior malignancies must be disease-free for ≥ 3 years.\n\nExclusion Criteria:\n\n1. Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug and temozolomide may be harmful to the developing fetus or nursing infant.\n2. Patients receiving concurrent therapy for their brain tumor (e.g., chemotherapeutics or investigational agents).\n3. Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for at least 3 years are eligible for this study.\n4. Patients who have had repeat craniotomy for tumor therapy after receiving radiation therapy and temozolomide treatment.\n5. Patients who received other chemotherapeutics or investigational agents in addition to their radiation therapy and concomitant temozolomide treatment.\n6. Patient has previously taken ruxolitinib or is allergic to components of the study drug.\n7. Patients using warfarin.\n8. Uncontrolled immunodeficiency virus infection or active tuberculosis.\n9. Patients with active serious infections requiring systemic therapy.\n10. Known Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Participants with previous positive serology results must have negative polymerase chain reaction results.\n11. Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, New York Heart Association (NYHA) Grade ≥2 heart failure, uncontrolled hypertension, valvular disease, pericarditis, myocardial infarction, or other thrombosis events like including pulmonary embolism or deep vein thrombosis within 6 months of screening.\n12. Any other serious medical\u002Fpsychiatric condition, in the judgement of the investigator, that likely to interfere or limit compliance with study requirements\u002Ftreatment.",{"count":128,"type":20},190,[80],"The purpose of this research is to test the safety and effectiveness of the investigational drug ruxolitinib when it is combined with standard of care treatment (radiation therapy and temozolomide) for the treatment of newly diagnosed glioblastoma. Half the people in the study will be assigned to take the study drug ruxolitinib in addition to the standard of care temozolomide and radiation therapy and the other half will be assigned to the standard of care temozolomide and radiation therapy only. This assignment will be randomized in a 1-to-1 ratio, like the flip of a coin.",[54,132,133,134,135,27,84],"Brain Cancer","Glioblastoma Multiforme","Glioblastoma Multiforme of Brain","Glioblastoma Multiforme, Adult","2025-12-23",{"date":110,"type":32},{"date":139,"type":32},"2025-12-03",{"date":141,"type":20},"2030-12",{"name":143,"class":39},"Baptist Health South Florida",{"id":145,"slug":146,"hasResults":11,"nctId":147,"briefTitle":148,"officialTitle":149,"acronym":150,"eligibilityCriteria":151,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":152,"targetDuration":4,"studyType":21,"phases":154,"briefSummary":155,"conditions":156,"keywords":4,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":159,"lastUpdatePostDateStruct":160,"startDateStruct":162,"completionDateStruct":164,"leadSponsor":166,"locationsCount":69},"100509145","phase-2-crizanlizumab-alone-or-in-combination-with-nivolumab-for-glioblastoma-and-melanoma-with-brain-metastases-100509145","NCT05909618","Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases","An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases","14","Cohort 1 (MBM) Inclusion Criteria\n\n1. Age ≥ 18 years.\n2. Estimated life expectancy at least 3 months\n3. Have metastatic melanoma with primarily diagnosed or newly progressing brain metastases.\n4. Was treated with 1 prior systemic line of immunotherapy - either PD-1 inhibitor monotherapy or combined CTLA4 and PD-1 antibodies or another investigational combination of immunotherapy. Patients with BRAF-mutant melanoma who have also received BRAF mutation targeted therapy are also eligible.\n5. Have failed prior immunotherapy line, either due to primary resistance or acquired resistance.\n6. Have measurable disease defined by RECIST criteria and have at least one, non-previously irradiated brain metastasis of at least 1-cm short diameter. Otherwise, previously irradiated lesions should present with enlargement following radiation therapy.\n7. Is clinically stable with no neurological deficits. Patients may receive steroid supportive therapy up to 10 mg of prednisone or the equivalent.\n8. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n9. Adequate organ function defined by blood tests for blood count and chemistry.\n10. Women of childbearing potential practicing an acceptable method of birth control.\n11. Understand study procedures and willingness to comply for the entire duration of the study and to give written informed consent.\n\n    Exclusion Criteria\n12. Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 10 mg prednisone will be allowed\n13. Have leptomeningeal spread.\n14. Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.\n15. Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.\n16. Previous exposure to Crizanlizumab or any other P-selectin inhibitor.\n17. Previous or current brain hemorrhage.\n18. The patient had, or is expected to undergo, allogeneic hematopoietic stem cell transplantation (HSCT).\n19. The patient had a contraindication for undergoing brain MRI.\n20. Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.\n21. Pregnant or lactating\n22. Treatment with other investigational drugs within \\\u003C21 days of start of day 1 of the study treatment.\n23. Any contraindication for treatment with nivolumab according to the product's labels.\n\nCohort 2 (Recurrent or Progressive GB) Inclusion Criteria\n\n1. Age ≥ 18 years.\n2. Estimated life expectancy at least 3 months\n3. Have with recurrent or persistent GB\n4. Received first line therapy with brain irradiation and maintenance temozolamide.\n5. Measurable disease per RANO criteria on brain MRI.\n6. Have Eastern Cooperative Oncology Group (ECOG) performance status \\\u003C2.\n7. Adequate organ function defined by blood tests for blood count and chemistry.\n8. Women of childbearing potential practicing an acceptable method of birth control.\n9. Understand study procedures and willingness to comply for the entire duration of the study and to give written informed consent.\n\nExclusion Criteria\n\n1. Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 20 mg prednisone will be allowed\n2. Have leptomeningeal spread.\n3. Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.\n4. Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.\n5. Previous exposure to Crizanlizumab or any other P-selectin inhibitor.\n6. Previous or current brain hemorrhage.\n7. The patient had, or is expected to undergo, allogeneic HSCT.\n8. The patient had a contraindication for undergoing brain MRI.\n9. Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.\n10. Pregnant or lactating\n11. Treatment with other investigational drugs within \\\u003C21 days of start of day 1 of the study treatment.\n12. Any contraindication for treatment with nivolumab according to the product's labels.\n\nCohort 3 (Newly Diagnosed Unmethylated GB) Inclusion Criteria\n\n1. Age ≥ 18 years.\n2. Estimated life expectancy at least 3 months.\n3. Histologically confirmed newly diagnosed GB.\n4. Tumor test result shows MGMT unmethylated type.\n5. Received definitive brain irradiation.\n6. Patients may be treated with novo TTF (optune) per local standard.\n7. Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.\n8. Adequate organ function defined by blood tests for blood count and chemistry.\n9. Women of childbearing potential practicing an acceptable method of birth control.\n10. Understand study procedures and willingness to comply for the entire duration of the study and to give written informed consent.\n\nExclusion Criteria\n\n1. Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 20 mg prednisone will be allowed\n2. Have leptomeningeal spread.\n3. Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.\n4. Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.\n5. Previous exposure to Crizanlizumab or any other P-selectin inhibitor.\n6. Previous or current brain hemorrhage.\n7. The patient had, or is expected to undergo, allogeneic HSCT.\n8. The patient had a contraindication for undergoing brain MRI.\n9. Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.\n10. Be pregnant or lactating\n11. Treatment with other investigational drugs within \\\u003C21 days of start of day 1 of the study treatment.\n\nAny contraindication for treatment with nivolumab according to the product's labels",{"count":153,"type":20},33,[80],"A single-center, open-label, non-randomized phase I\u002FII study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.\n\nSubjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:\n\nCohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.\n\nCohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.\n\nCohort 3: Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.",[157,158,27],"Advanced Glioblastoma","Metastatic Melanoma in the Central Nervous System","2025-07-17",{"date":161,"type":32},"2025-07-22",{"date":163,"type":32},"2023-07-11",{"date":165,"type":20},"2030-07-30",{"name":167,"class":168},"Sheba Medical Center","OTHER_GOV"]