Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma (PRIDE)

Ludwig Maximilian University of Munich

Status and phase

Enrolling

Phase 2

Conditions

Glioblastoma

Treatments

Radiation: Dose escalation of radiation dose beyond the therapeutic standard

Study type

Interventional

Funder types

Other

Identifiers

NCT05871021

2021-000565-32

Details and patient eligibility

About

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.

Enrollment

146 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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