Clinical trial NCT05871021: Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Glioblastoma
Keywords: Dose escalation
bevacizumab
VEGF inhibition
FET PET
VMAT
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2023-05-23
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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 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

Primary outcomes:
measure: OS
timeFrame: Date of study inclusion (informed consent) to death or end of F/U
Secondary outcomes:
measure: Safety and tolerability
timeFrame: Date of study inclusion (informed consent) to death or end of F/U
measure: PFS-6
timeFrame: 6 months after the date of study inclusion (informed consent)
measure: PFS
timeFrame: Date of study inclusion (informed consent) to death or progression
measure: QoL
timeFrame: Date of study inclusion (informed consent) to death or end of F/U
measure: Cognitive function
timeFrame: Date of study inclusion (informed consent) to death or end of F/U
measure: Exploratory objective
timeFrame: Date of study inclusion (informed consent) to death or end of F/U
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Radiation Oncology
Study officials:
affiliation: University Hospital, LMU Munich
name: Maximilian Niyazi, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: