Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma
Phase 2
Recruiting
- Conditions
- Glioblastoma
- Interventions
- Radiation: Dose escalation of radiation dose beyond the therapeutic standard
- Registration Number
- NCT05871021
- Lead Sponsor
- Ludwig-Maximilians - University of Munich
- Brief Summary
Glioblastoma is the most aggressive brain tumor and often recurs locally despite intensive treatment. Standard chemoradiotherapy with 60 Gy may not be sufficient to control the tumor, and dose escalation seems to be warranted, but causes more toxicity. To address this, the multicentric PRIDE trial employs two cycles of bevacizumab to achieve dose escalation isotoxically. The goal is improved survival without significantly increasing side effects. The study uses a simultaneous integrated boost with a total dose of 75 Gy in 2.5 Gy per fraction.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 146
Inclusion Criteria
- IDH wild-type, MGMT unmethylated glioblastoma patients
- Informed consent
- Age ≥18 and ≤ 70 years, smoking or non-smoking, of any ethnic origin
- ECOG 0-2
- Neutrophil counts > 1500/μl; Platelet counts > 100.000/μl; Hemoglobin > 8 g/dl; Serum creatinine < 1.5-fold upper limit of normal (ULN); Bilirubin, AST or ALT < 2.5-fold ULN unless attributed to anticonvulsants; Alkaline phosphatase < 2.5-fold ULN
- Adequate contraception
- Serum creatinine ≤ 1.5 x ULN AND patients with urine dipstick for proteinuria < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should show urine protein to creatinine ratio ≤ 1
Exclusion Criteria
- Evidence of recent hemorrhage on postoperative MRI of the brain
- Subjects on any drug suspected to interfere with bevacizumab at the time of study inclusion
- Immuno-compromised patients, including known seropositivity for human immunodeficiency virus (HIV)
- Known hypersensitivity to any component of the investigational drugs or excipients (allergy to or other intolerability of bevacizumab or excipients)
- 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
- Incapability to undergo MRI
- Prior treatment with bevacizumab for any indication
- 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
- Inadequately controlled hypertension (de-fined 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
- History of stroke or transient ischemic attack within 6 months prior to enrolment
- Significant vascular disease (e.g. aortic aneurysm, aortic dissection or recent peripheral arterial thrombosis) within 6 months prior to enrolment
- Evidence or history of recurrent thromboembolism (> 1 episode of deep venous thrombosis / peripheral embolism) during the past 2 years
- Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
- Chronic daily intake of aspirin > 325 mg/day or clopidogrel > 75 mg /day
- History of intracranial abscess within 6 months prior to inclusion
- History of abdominal or tracheo-oesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrolment
- History of ≥ grade 2 hemoptysis according to NCI-CTC criteria within 1 month prior to inclusion
- Serious non-healing wound, ulcer or bone fracture
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 75 Gy with two cycles of bevacizumab Dose escalation of radiation dose beyond the therapeutic standard -
- Primary Outcome Measures
Name Time Method OS Date of study inclusion (informed consent) to death or end of F/U Overall Survival
- Secondary Outcome Measures
Name Time Method Safety and tolerability Date of study inclusion (informed consent) to death or end of F/U Safety and tolerability of dose escalation with bevacizumab according to CTCAE v5.0
PFS Date of study inclusion (informed consent) to death or progression Progression-free survival
PFS-6 6 months after the date of study inclusion (informed consent) 6 months rate of progression-free survival
Exploratory objective Date of study inclusion (informed consent) to death or end of F/U Validation of prognostic 4-miRNA signature-based risk score
QoL Date of study inclusion (informed consent) to death or end of F/U Quality of life as determined by EORTC QLQ-C30/QLQ-BN 20
Cognitive function Date of study inclusion (informed consent) to death or end of F/U Cognitive function determined by standard test batteries
Trial Locations
- Locations (1)
Department of Radiation Oncology
🇩🇪Munich, Germany