Using VEGF inhibition to safely increase radiation doses in glioblastoma treatment
A Phase IIa, Open-label, Multicenter Study of Radiochemotherapy With Isotoxic Dose Escalation and Protective VEGF Inhibition Using Bevacizumab in the Treatment of Patients With First Diagnosis of IDH Wild-type, MGMT Unmethylated Glioblastoma
This study is testing if giving a drug called bevacizumab can help people with glioblastoma safely receive higher doses of radiation therapy to improve their chances of survival.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 146 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | University Hospital Tuebingen Academic / other |
| Drugs / interventions | bevacizumab |
| Locations | 1 site (Tübingen) |
| Trial ID | NCT05871021 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to improve treatment outcomes for patients with glioblastoma by employing bevacizumab to enable isotoxic dose escalation of radiation therapy. The study will administer two cycles of bevacizumab to allow for a total radiation dose of 75 Gy, delivered in 2.5 Gy fractions, while minimizing side effects. The goal is to enhance survival rates without significantly increasing toxicity compared to standard treatment. Participants will be closely monitored for both efficacy and safety throughout the trial.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 to 70 with IDH wild-type, MGMT unmethylated glioblastoma who meet specific health criteria.
Not a fit: Patients with recent brain hemorrhage, those on conflicting medications, or immunocompromised individuals may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could lead to improved survival rates for glioblastoma patients with manageable side effects.
How similar studies have performed: While the approach of dose escalation in glioblastoma is being explored, this specific method of combining VEGF inhibition with radiation is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
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 significant hemorrhage on postoperative MRI of the brain. Patients with asymptomatic, minor hemosiderin deposition, resolving postsurgical hemorrhagic changes, 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 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 * Contraindication and/or hypersensitivity to bevacizumab or its excipients. For details check the Summary of Product Characteristics Aybintio® * 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 (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 * History of clinically significant cerebrovascular events within 6 months prior to enrolment. 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 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
Where this trial is running
Tübingen
- Department of Radiation Oncology — Tübingen, Germany (Recruiting)
Study contacts
- Principal investigator: Maximilian Niyazi, Prof. Dr. — University Hospital Tuebingen, Department of Radiation Oncology
- Study coordinator: Barbara Gehler, Dr. med.
- Email: pride_tuebingen@med.uni-tuebingen.de
- Phone: +49 7071 29 83420
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.