Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma

Phase

Condition

Gliomas

Astrocytoma

Treatment

Dose escalation of radiation dose beyond the therapeutic standard

Clinical Study ID

NCT05871021

2021-000565-32

Ages 18-70
All Genders

Study 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.

Eligibility Criteria

Inclusion

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, Serumcreatinine <1.5-fold upper limit of normal (ULN), Bilirubin, AST or ALT <2.5-foldULN 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 urineprotein to creatinine ratio ≤ 1

Exclusion

Exclusion Criteria:

Evidence of significant hemorrhage on postoperative MRI of the brain. Patients withasymptomatic, minor hemosiderin deposition, resolving postsurgical hemorrhagicchanges, or punctate intratumoral hemorrhage (e.g., related to biopsy or surgery)are not excluded
Subjects on any drug suspected to interfere with bevacizumab at the time of studyinclusion
Immuno-compromised patients, including known seropositivity for humanimmunodeficiency 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 findingthat would, in the investigator's judgement, make the patient inappropriate for thisstudy, or would increase the risk associated with the patients' participation in thestudy
Incapability to undergo MRI
Prior treatment with bevacizumab for any indication
Contraindication and/or hypersensitivity to bevacizumab or its excipients. Fordetails check the Summary of Product Characteristics Aybintio®
Significant cardiovascular disease defined as congestive heart failure (NYHA ClassII, III, IV), unstable angina pectoris, or myocardial infarction within 6 monthsprior to enrolment
Inadequately controlled hypertension (defined as a blood pressure of > 150 mmHgsystolic and/or >100 mmHg diastolic on medication), or any prior history ofhypertensive crisis or hypertensive encephalopathy
History of clinically significant cerebrovascular events within 6 months prior toenrolment. This includes ischemic stroke or transient ischemic attack. Small,clinically silent perioperative ischemic changes are not exclusionary.
Significant vascular disease (e.g. aortic aneurysm, aortic dissection or recentperipheral arterial thrombosis) within 6 months prior to enrolment
Evidence or history of recurrent thromboembolism (> 1 episode of deep venousthrombosis / peripheral embolism) during the past 2 years
Evidence of bleeding diathesis or coagulopathy (in the absence of therapeuticanticoagulation)
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 priorto inclusion
Serious non-healing wound, ulcer or bone fracture

Study Design