PRIDE: Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma

Sponsor

Ludwig-Maximilians - University of Munich (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05871021

Collaborator

(none)

146

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Radiation: Dose escalation of radiation dose beyond the therapeutic standard	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

146 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2026

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 75 Gy with two cycles of bevacizumab	Radiation: Dose escalation of radiation dose beyond the therapeutic standard Dose escalation to 75 Gy with concomitant radioprotectant bevacizumab Other Names: bevacizumab

Arm

Intervention/Treatment

Experimental: 75 Gy with two cycles of bevacizumab

Radiation: Dose escalation of radiation dose beyond the therapeutic standard

Dose escalation to 75 Gy with concomitant radioprotectant bevacizumab

Other Names:

bevacizumab

Outcome Measures

Primary Outcome Measures

OS [Date of study inclusion (informed consent) to death or end of F/U]
Overall Survival

Secondary Outcome Measures

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-6 [6 months after the date of study inclusion (informed consent)]
6 months rate of progression-free survival
PFS [Date of study inclusion (informed consent) to death or progression]
Progression-free survival
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
Exploratory objective [Date of study inclusion (informed consent) to death or end of F/U]
Validation of prognostic 4-miRNA signature-based risk score

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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