Glioblastoma MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Bevacizumab
Pharmaceutical Form:
INN or Proposed INN: Bevacizumab
CAS Number: 216974-75-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number:
Sponsors
Klinikum der Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Diagnosis of glioblastoma, IDH-wildtype and MGMT unmethylated status must be proven histologically. MRI images must not be older than 2 weeks before initiating RT 2. = 18 and = 70 years of age, smoking or non-smoking, of any ethnic origin 3.Eastern Cooperative Oncology Group (ECOG) Performance Status 0–2 4.Patient must have provided signed informed consent (informed consent document to be approved by the institution’s Independent Ethics Committee and consent obtained prior to any study-specific procedure). This includes the willingness to give written informed consent, written consent for data protection (according to the German General Data Protection Regulation (Datenschutz-Grundverordnung, DSGVO) in addition to willingness to participate and comply with the study. 5.Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of inclusion 6.Adequate hematological function: white blood cell (WBC) count ? 3x109/L, absolute neutrophil count (ANC) >1,5x109/L, platelet count 100x109/L, hemoglobin = 8 g/dl (may be obtained by the use of erythropoietin-stimulating agents or transfusion for anemia) 7.Adequate liver function: Total bilirubin 2 weeks at time of enrolment. Therefore, during the study, the preferred choice for anticoagulation treatment with therapeutic intent should be low molecular weight heparin as per ASCO guidelines. 10.Women of childbearing potential (i.e., a woman, who is biologically capable of becoming pregnant) must have a negative serum (ß-HCG) pregnancy test within 7 days prior to the first dose of study medication and radiotherapy; adequate contraception should be applied. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 136 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Positive test results for HbsAG, anti-HCV, anti-HIV-1/-2 2. Any other condition or treatment that, in the opinion of the Investigator, might interfere with the study or current drug 3. Controlled substance abuse according to the German Narcotic Drugs Act (Betäubungsmittelgesetz, BtMG) 4. Past medical history of diseases with poor prognosis according to the judgement of the investigator, e.g. severe coronary heart disease, severe diabetes, immune deficiency, residual deficits after stroke, severe mental retardation 5. Foreseeable non-compliance with the protocol requirements, instructions and study-related restrictions, e.g. uncooperative attitude, inability to return for follow-up visits, and low probability of completing the study 6. Pregnancy or breast feeding 7. Patient is the investigator, research assistant, pharmacist, study coordinator, other staff or relative there of directly involved in the conduct of the study. 8. Evidence of recent hemorrhage on postoperative MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor are permitted entry into the study 9. Any prior radiotherapy to the brain or prior radiotherapy resulting in a potential overlap in the radiation field 10. Patients simultaneously enrolled in another clinical trial or patients who participated in another clinical trial during the 28 days (or five-half lives of the respective investigational product, whichever is longer) before enrolment 11.Patients who previously participated in this trial 12.Evidence for any active infection requiring hospitalization or i.v. antibiotics within 2 weeks prior to inclusion 13.Patients who are underage or patients who are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 und Abs. 3 AMG). 14.Patients who possibly are dependent on the sponsor or investigator. 15.Immuno-compromised patients, including known seropositivity for human immunodeficiency virus (HIV) 16.History of chronic gastrointestinal disease with diarrhea; history of abdominal or pelvic radiotherapy 17.Any other significant medical illness or medically significant laboratory finding that would, in the investigator’s judgement, make the patient inappropriate for this study, or would increase the risk associated with the patients’ participation in the study 18.Inability to undergo MRI 19.Contraindication and/or hypersensitivity to bevacizumab or its excipients. For details check the Summary of Product Characteristics of Aybintio® 20.Prior treatment with bevacizumab for any indication 21.Parallel administration of any drug suspected to interfere with bevacizumab at the time of inclusion 22.Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, III, IV), unstable angina pectoris or myocardial infarction within 6 months prior to enrolment 23. Inadequately controlled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or >100 mmHg diastolic on medication) or any prior history of hypertensive crisis or hypertensive encephalopathy 24. History of stroke or transient ischemic attack within 6 months prior to enrolment 25. Significant vascular disease (e.g., aortic aneurysm, aortic dissection or recent peripheral arterial thrombosis) within 6 months prior to enrolment 26.Evidence or history of recurren
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall survival;Secondary Objective: Safety and tolerability of isotoxic dose escalation and bevacizumab Progression-free survival after 6 months (PFS-6) Progression-free survival (PFS) Quality of life as determined by EORTC QLQ-C30 and the EORTC brain module QLQ-BN 20. Cognitive function as determined by MMSE and MOCA Exploratory objective: validation of 4-miRNA signature-based risk subgroups in FFPE material and plasma samples ;Primary end point(s): Overall survival after 2 years;Timepoint(s) of evaluation of this end point: 2 years after study inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Safety and tolerability of isotoxic dose escalation and bevacizumab •Progression-free survival after 6 months (PFS-6) •Progression-free survival (PFS) •Quality of life as determined by EORTC QLQ-C30 and the EORTC brain module QLQ-BN 20. •Cognitive function as determined by MMSE and MOCA • Exploratory objective: validation of 4-miRNA ;Timepoint(s) of evaluation of this end point: After 2 years | — |
Countries
Germany
Contacts
Public ContactDr. med. Christiane Blankenstein
Münchner Studienzentrum der TU München Fakultät für Medizin
Outcome results
None listed