[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100303667":3},{"organization":4,"armGroups":7,"interventions":16,"overallOfficials":28,"centralContacts":28,"locations":34,"responsibleParty":46,"collaborators":28,"id":50,"slug":51,"hasResults":52,"nctId":53,"briefTitle":54,"officialTitle":55,"acronym":56,"eligibilityCriteria":57,"healthyVolunteers":52,"sex":58,"minAge":59,"maxAge":28,"enrollmentInfo":60,"targetDuration":28,"studyType":63,"phases":64,"briefSummary":67,"conditions":68,"keywords":70,"overallStatus":72,"whyStopped":28,"lastUpdateSubmitDate":73,"lastUpdatePostDateStruct":74,"startDateStruct":76,"completionDateStruct":78,"leadSponsor":81,"locationsCount":82},{"fullName":5,"class":6},"Universitair Ziekenhuis Brussel","OTHER",[8],{"label":9,"type":10,"description":11,"interventionNames":12},"ipilimumab + nivolumab + CD1c (BDCA-1)+ myDC and CD141 (BDCA-3)+ myDC","EXPERIMENTAL","Phase I CD1c(BDCA-1)+\u002FCD141(BDCA-3)+ myDC dose escalation (: 3 predefined dose levels) part of the study: to document the safety of peroperative injection of an escalating number of autologous CD1c(BDCA-1)+\u002FCD141(BDCA-3)+ myDC plus IT injection of nivolumab and ipilimumab, following tumor resection.\n\nPhase II part of the study: to document the anti-tumor activity of peroperative injection of a defined number of autologous CDC1(BDCA-1)+\u002FCD141(BDCA-3)+myDC. Ipilimumab (YervoyTM, 50 mg\u002F10 mL) and Nivolumab (OpdivoTM, 40 mg\u002F4mL solution) will be administered peroperatively at a dose of injection of 10 mg (2 ml of YervoyTM, 50 mg\u002F10mL vial). as well as intracavitary on days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169.\n\n10 mg Nivolumab by the intravenous route will be administered by a 15 minutes intravenous infusion on days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169. (or up to ± 3 days before or after the scheduled date if necessary).",[13,14,15],"Drug: Ipilimumab (YervoyTM, 50 mg\u002F10 mL solution)","Drug: Nivolumab (OpdivoTM, 40 mg\u002F4mL solution)","Biological: Autologous CD1c(BDCA-1)+ \u002FCD141(BDCA-3)+ myDC",[17,24,29],{"type":18,"name":19,"description":20,"armGroupLabels":21,"otherNames":22},"DRUG","Ipilimumab (YervoyTM, 50 mg\u002F10 mL solution)","Ipilimumab will be administered by at the end of the neurosurgical resection procedure at a dose of injection of 10 mg (: 2 ml of YervoyTM, 50 mg\u002F10mL vial).\n\nInjections will be performed manually using a 100 μ-liter dispensing syringe. Twenty needle tracks will dispense the ipilimumab solution within the brain tissue lining the resection cavity. The region suspect on preoperative MRI of the brain to be invaded by glioblastoma cells but not amenable to safe resection will be targeted by adjacent needle tracks through which up to 2 cm of depth a volume of 100 μl per needle track will be injected (: in total 20 needle tracks will be performed). This methodology has been applied previously within the context of phase III clinical trials with sitimagene ceradenovec.",[9],[23],"Nivolumab (OpdivoTM, 40 mg\u002F4 mL solution)",{"type":18,"name":25,"description":26,"armGroupLabels":27,"otherNames":28},"Nivolumab (OpdivoTM, 40 mg\u002F4mL solution)","First administration of 10 mg of nivolumab by the intravenous route should be administered within 24 hours prior to the planned neurosurgical resection. Administrations of 10 mg nivolumab (OpdivoTM, 40 mg\u002F4mL solution) will be by a 15 minutes intravenous infusion on days 15, 29, 43, 57, and 71 (or up to ± 3 days before or after the scheduled date if necessary).",[9],null,{"type":30,"name":31,"description":32,"armGroupLabels":33,"otherNames":28},"BIOLOGICAL","Autologous CD1c(BDCA-1)+ \u002FCD141(BDCA-3)+ myDC","Autologous CD1c(BDCA-1)+\u002FCD141(BDCA-3)+ myDC will be isolated from PBMC obtained from the leukapheresis. These are injected in the neighbouring brain tissue post tumor resection.",[9],[35],{"facility":5,"status":28,"city":36,"state":28,"zip":37,"country":38,"countryCode":39,"cosmosGeoPoint":40,"geoPoint":45,"contacts":28},"Brussels","1090","Belgium","BE",{"type":41,"coordinates":42},"Point",[43,44],4.34878,50.85045,{"lat":44,"lon":43},{"type":47,"investigatorFullName":48,"investigatorTitle":49,"investigatorAffiliation":5,"oldNameTitle":28,"oldOrganization":28},"PRINCIPAL_INVESTIGATOR","Bart Neyns","Head of Medical Oncology","100303667","phase-1-a-phase-iii-clinical-trial-on-the-per-operative-intratumoral-administration-of-myeloid-dendritic-cells-plus-ipilimumab-and-nivolumab-followed-by-repeated-intracavitary-plus-intravenous-administration-of-nivolumab-in-patients-with-recurrent-glioblastoma-100303667",false,"NCT03233152","A Phase I\u002FII Clinical Trial on the Per-operative Intratumoral Administration of Myeloid Dendritic Cells Plus Ipilimumab and Nivolumab, Followed by Repeated Intracavitary Plus Intravenous Administration of Nivolumab in Patients With Recurrent Glioblastoma.","A Phase I\u002FII Clinical Trial on the Per-operative Intratumoral Administration of Myeloid Dendritic Cells Plus Ipilimumab and Nivolumab, Followed by Repeated Intracavitary Plus Intravenous Administration of Nivolumab in Patients With Recurrent Glioblastoma","GlitIpNi","1. Subjects must have signed and dated an approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care\n2. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.\n3. Histopathological diagnosis of glioblastoma (= WHO grade IV glioma of the central nervous system); both patients with \"de novo\" and \"secondary\" glioblastoma are eligible; patients who have histological proof of a lower-grade glioma (WHO grade I, II or III) and have evidence for transformation to WHO-grade IV glioma on imaging of the brain (gadolinium enhancement, areas of necrosis) are eligible for study participation;\n4. Diagnosis of glioblastoma recurrence and\u002For progression following prior treatment with surgery consisting of a total or partial tumor resection, radiation therapy and temozolomide chemotherapy (recurrence\u002Fprogression is defined as significant \\[according to the investigators assessment\\] growth and\u002For recurrence of the glioblastoma tumor mass on sequential MRI of the brain);\n5. The following disease characteristics should be present:\n\n   1. Presence of a measurable tumor lesion that is characterized by gadolinium enhancement on T1-MRI of the brain (with a longest diameter of \\> 10 mm and a perpendicular diameter of \\>5mm).\n   2. No evidence of clinically relevant spontaneous intra-tumor hemorrhage on baseline MRI imaging or in the prior disease history\n6. No ventriculo-peritoneal drain\n7. No contraindication for evaluation by gadolinium enhanced MRI, FET-PET of the brain or whole-body contrast enhanced CT;\n8. ECOG performance status score of 0, 1 or 2;\n9. An interval of at least 4 months (: 16 weeks) after the end of postoperative radiation therapy for glioblastoma unless progression is confirmed on an MRI of the brain obtained \\> 4 week after the first observation of progression; and with an interval of at least 4 weeks after the last administration of temozolomide;\n10. Male or female, 18 years of age or older;\n11. Resolution of all acute treatment related adverse effects of prior surgical procedures, radiotherapy and temozolomide to NCI CTCAEv4.0 grade 0 or 1 except for alopecia;\n12. Adequate organ function as defined by the following criteria:\n\n    1. Total serum bilirubin \\\u003C 1.5 x ULN (patients with Gilbert's disease exempt who should have bilirubin \\\u003C 2x ULN)\n    2. AST and ALT \\\u003C 2.5 x upper limit of normal (ULN);\n    3. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL\u002Fmin\n    4. Absolute neutrophil count (ANC) \\> 1500\u002Fmm³ without growth factor support\n    5. Platelets \\> 75 000 cells\u002Fmm³\n    6. Hemoglobin ≥9 g\u002FdL (which may be obtained by transfusion or growth factor support)\n    7. FT4 hormone levels within normal range\n13. No prior treatment on a nivolumab and\u002For ipilimumab trial;\n14. No prior treatment with an anti-CTLA-4 or anti-PD-1\u002F-L1 targeted therapy\n15. No gastrointestinal abnormalities including:\n\n    1. Inability to take oral medication.\n    2. Requirement for intravenous alimentation.\n    3. Prior surgical procedures affecting absorption including gastric resection.\n    4. Treatment for active peptic ulcer disease in the past 6 months.\n    5. Malabsorption syndromes.\n    6. Active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;\n16. No evidence of pre-existing uncontrolled hypertension as documented by baseline blood pressure reading. The baseline systolic blood pressure reading must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. If baseline blood pressure reading exceeds the inclusion values a second blood pressure reading (taken at least 1 hour apart) must be documented in order to confirm the absence of uncontrolled hypertension. Patients whose hypertension is controlled by antihypertensive therapies are eligible;\n17. No concurrent treatment:\n\n    1. In another therapeutic clinical trial;\n    2. No requirement for permanent therapeutic anticoagulation therapy.\n18. Subjects with active, known, or suspected autoimmune disease are not eligible. Subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.\n19. Subjects requiring systemic treatment with either corticosteroids (\\> 8 mg daily methylprednisolone equivalent) or other immunosuppressive medications within 14 days of study enrollment. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.\n20. Adequate venous access to undergo a leukapheresis procedure.\n21. No active uncontrolled seizure disorder.\n22. No myocardial infarction, severe\u002Funstable angina, coronary\u002Fperipheral artery bypass graft, symptomatic congestive heart failure or any unstable arrhythmia, cerebrovascular accident or transient ischemic attack, within the 12 months prior to study drug administration. No current or recent (within 1 month) use of a thrombolytic agent or a thrombo-embolic event;\n23. No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness;\n24. No serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment;\n25. No history of a malignancy (other than glioma) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years;\n26. No other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study;\n27. No dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol;\n28. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.; Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception measures during the period of therapy which should be continued for 12 weeks after the last dose of nivolumab. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate; No pregnancy or breastfeeding; a) No contra-indication for neurosurgical resection of the glioblastoma recurrence.","ALL","18 Years",{"count":61,"type":62},110,"ACTUAL","INTERVENTIONAL",[65,66],"PHASE1","PHASE2","Phase I\u002FII clinical trial on the per-operative intra-tumoral administration of myeloid dendritic cells plus ipilimumab and nivolumab, followed by repeated intracavitary administration of ipilimumab and nivolumab plus intravenous administration of nivolumab in patients with recurrent glioblastoma.\n\nThe aim of this clinical trial is to exploit the potential synergy of combined intra-tumoral CTLA-4 and autologous CD1c(BDCA-1)+\u002FCD141(BDCA-3)+ myDC and systemic PD-1 blockade while minimizing the risk for increased immune-related toxicity by intratumoral administration of the CTLA-blocking mAb ipilimumab following the resection of the recurrent glioblastoma.",[69],"Glioblastoma",[71],"recurrence","ACTIVE_NOT_RECRUITING","2025-11-17",{"date":75,"type":62},"2025-11-21",{"date":77,"type":62},"2016-11-17",{"date":79,"type":80},"2026-11-17","ESTIMATED",{"name":5,"class":6},1]