BEVACIZUMAB for Brain radionecrosis | Brain metastases

Inclusion criteria

• {"criterion_text":"- 1.\tPatient with a diagnosis of radionecrosis based on a clinical onset of symptoms and radiological findings of RN following radiotherapy, with or without pathological confirmation: o\tMRI evidence to support the diagnosis of RN (transient increase in irradiated lesion volume -FLAIR hypersignal and/or enhanced portion- without rCBV increase) o\tCOMBINED with nuclear medicine imaging: \t biphasic 18FDG-PET-TDM/MRI according to Horky or \t 18F-FDOPA PET TDM/MRI with stage 0-1 according to Lizarraga"}
• {"criterion_text":"- 2.\tSymptoms are persistent or worsening despite administration of corticosteroids: at least 1 mg/kg/d of prednisolone or equivalent: -\tCorticoresistant: neurological symptoms despite administration of at least 2 weeks of 1 mg/kg/d prednisolone or equivalent; -\tCorticodependant: worsening of neurological signs or symptoms after an initial improvement when weaning off steroids at a dose < 0.5 mg/kg/d prednisolone or equivalent;"}
• {"criterion_text":"- 3.\tPatients must have received the last cranial irradiation with photons or proton therapy for brain metastases ≥ 3 months with one or more sequences;"}
• {"criterion_text":"- 4.\tAge ≥ 18-year-old;"}
• {"criterion_text":"- 5.\tECOG performance status score ≤ 2 or Karnofsky Performance Score (KPS) ≥ 50"}
• {"criterion_text":"- 6.\tLife expectancy of at least 3 months assessed by graded prognostic score (DS-GPA) score 0.5 or greater;"}
• {"criterion_text":"- 7.\tPatient who has never received Bevacizumab for the indication of radionecrosis."}
• {"criterion_text":"- 8.\tAdequate organ function: Bone marrow function •\tAbsolute Neutrophil Count (ANC) ≥ 1,500/mm3 Platelet Count ≥ 100,000/mm3, Haemoglobin ≥ 10 g/dL (allowing transfusion or other intervention to achieve this minimum haemoglobin) Coagulation •\tInternational normalized ratio (INR) or prothrombin time < 1.5 × ULN Renal function •\tNo proteinuria with urine dipstick for proteinuria > 2+ •\tSerum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min (measured or calculated using the CDK-EPI formula) Hepatic Function •\tTotal bilirubin ≤1.5 x the upper limit of normal (ULN) •\tAlanine transaminase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN"}
• {"criterion_text":"- 9. Women of childbearing potential must use effective contraceptive measures during the treatment and for 6 months following its cessation"}
• {"criterion_text":"- 10.\tSigned informed consent;"}
• {"criterion_text":"- 11.\tPatient affiliated to a social security scheme."}

Exclusion criteria

• {"criterion_text":"- 1.\tEvidence of active bleeding or a pathological condition at high risk of bleeding: CNS hemorrhage, bleeding diathesis or coagulopathy, hemoptysis (>2.5ml of bright red blood per episode), evidence of history of bowel obstruction, abdominal fistula, or gastrointestinal tract perforation or gastro intestinal abscess occurring less than 28 days prior study entry"}
• {"criterion_text":"- 2.\tGrade 4 venous thromboelism and peripheral arterial thrombus;"}
• {"criterion_text":"- 3.\tEvidence of very high intracranial pressure that suggests brain hernia and needs emergency surgery;"}
• {"criterion_text":"- 4.\tMajor surgical procedure or significant traumatic injury less than 28 days prior study entry; minor surgery within 3 days prior to initiation of study treatment;"}
• {"criterion_text":"- 5.\tClinically significant cardiovascular disease such as uncontrolled arterial hypertension (BP ≥160 mm Hg or diastolic BP ≥100 mm Hg despite maximal medical therapy), cerebrovascular event, myocardial infarction, cardiac arrhythmias, unstable angina, or congestive heart failure within the last 6 months;"}
• {"criterion_text":"- 6.\tHistory of hypertensive crisis or hypertensive encephalopathy"}
• {"criterion_text":"- 7. Patients scheduled to undergo head and neck, thoracic, or abdominal radiotherapy during the study treatment"}
• {"criterion_text":"- 8.\tPrior bevacizumab ≤ 3 months before randomization;"}
• {"criterion_text":"- 9.\tProgressive brain metastases;"}
• {"criterion_text":"- 10.\tHistory of severe allergic anaphylactic reactions to bevacizumab"}
• {"criterion_text":"- 11.\tPatients with a known hypersensitivity to athe active substance or to any of the excipients of bevacizumab are not eligible for participation;"}
• {"criterion_text":"- 12.\tPatients with a contraindication to the treatment with bevacizumab according to the European SmPC"}
• {"criterion_text":"- 13.\tPatient pregnant and/or nursing;"}
• {"criterion_text":"- 14.\tMental impairment (psychiatric illness/social situations) that may compromise the ability of the patient to give informed consent and comply with the requirements of the study;"}
• {"criterion_text":"- 15.\tPatient who has forfeited his/her freedom by administrative or legal award or who is under guardianship."}
• {"criterion_text":"- 16.\tNew cerebral metastasis detected during the inclusion imaging evaluation;"}
• {"criterion_text":"- 17.\tPrior diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES) with bevacizumab;"}
• {"criterion_text":"- 18.\tHypersensitivity known to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies."}

Primary endpoints

• {"endpoint_text":"- Corticosteroids dose at Cycle 1 Day 1 (C1D1) and at 3 months (90 days, End of treatment (EOT) visit) - NANO (Neurological Assessment in Neuro-Oncology) score (60) at C1D1 and at 3 months (90 days -EOT visit) The NANO scale evaluates 8 major domains of neurologic function that are most relevant to patients with supratentorial, infratentorial, and brainstem tumors","definition_or_measurement_approach":"Corticosteroid dose measured at C1D1 and at 3 months (90 days, EOT visit). NANO score measured at C1D1 and at 3 months; NANO scale evaluates 8 major domains of neurologic function."}

Secondary endpoints

• {"endpoint_text":"- a) Safety assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 for up to 90 days following C1D1","definition_or_measurement_approach":"Safety assessed by NCI-CTCAE v5.0 up to 90 days following C1D1."}
• {"endpoint_text":"- b) Quality of life is measured with EORTC QLQ-C30 and BN20 (59) ; assessed at C1D1, C2D1, C3D1, C4D1 and EOT visit","definition_or_measurement_approach":"QoL measured by EORTC QLQ-C30 and BN20 at specified cycles (C1D1, C2D1, C3D1, C4D1) and EOT."}
• {"endpoint_text":"- c)\tSuccess assessed using: -\tCorticosteroid’s dose: at C1D1 and at 3 months (90 days) -\t NANO score: at C1D1, C2D1, C3D1, C4D1 and EOT visit -\tEORTC QLQC-30 and BN20 scores: at C1D1, C2D1, C3D1, C4D1 and EOT visit","definition_or_measurement_approach":"Composite success measures: corticosteroid dose, NANO score, and EORTC QLQ-C30/BN20 at listed timepoints."}
• {"endpoint_text":"- d)\tClinical changes assessed using: -\tPatient Global Impression of Change (PGIC) questionnaire (from 1 to 7) and Scale (from 0 to 10): at C4D1 and EOT visit -\tNANO score: at C1D1, C2D1, C3D1, C4D1 and EOT visit","definition_or_measurement_approach":"Clinical changes assessed by PGIC at C4D1 and EOT and by serial NANO scores at specified visits."}
• {"endpoint_text":"- e)\tvolume on brain MRI T1 post-gadolinium and T2-weighted FLAIR: at EOT visit","definition_or_measurement_approach":"MRI volumetric assessment on T1 post-gadolinium and T2-FLAIR at EOT."}
• {"endpoint_text":"- f)\tDuration of response assessed using: -\tNANO scale: every 3 months until 2 years -\tdose of corticosteroids: every 3 months until 2 years","definition_or_measurement_approach":"Duration of response measured by NANO scale and corticosteroid dose every 3 months up to 2 years."}
• {"endpoint_text":"- g)\tCorticosteroids dose at 3 months and vital status up to 3 months","definition_or_measurement_approach":"Corticosteroid dose at 3 months; vital status assessed up to 3 months."}
• {"endpoint_text":"- h)\tCorrelative biomarkers (ceramide, VEGF, angiopoietin, TGF-alpha) and nuclear medicine images","definition_or_measurement_approach":"Correlative biomarker analyses for listed biomarkers; nuclear medicine imaging assessments as ancillary studies."}

France

Earliest CTIS Part Ii Submission Date

19-04-2024

Latest Decision Or Authorization Date

20-03-2026

Processing Time Days

700

Number Of Sites

22

Number Of Participants

84

Primary sponsor

Full Name

Institut De Cancerologie De L Ouest

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France