Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma

Glioblastoma Clinical Trial

— PRIDE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05871021
• Other study ID #: 2021-000565-32
• Status: Recruiting
• Phase: Phase 2
• Start date: April 10, 2024
• Est. completion date: July 10, 2027

Study information

• Verified date: April 2024
• Source: Ludwig-Maximilians - University of Munich
• Contact: Ulrike Plugradt
• Phone: 004989440074770
• Email: Ulrike.Pflugradt[@]med.uni-muenchen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 146
• Est. completion date: July 10, 2027
• Est. primary completion date: April 10, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Radiation:
• Dose escalation of radiation dose beyond the therapeutic standard
Dose escalation to 75 Gy with concomitant radioprotectant bevacizumab

Locations

Country	Name	City	State
Germany	Department of Radiation Oncology	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OS	Overall Survival	Date of study inclusion (informed consent) to death or end of F/U
Secondary	Safety and tolerability	Safety and tolerability of dose escalation with bevacizumab according to CTCAE v5.0	Date of study inclusion (informed consent) to death or end of F/U
Secondary	PFS-6	6 months rate of progression-free survival	6 months after the date of study inclusion (informed consent)
Secondary	PFS	Progression-free survival	Date of study inclusion (informed consent) to death or progression
Secondary	QoL	Quality of life as determined by EORTC QLQ-C30/QLQ-BN 20	Date of study inclusion (informed consent) to death or end of F/U
Secondary	Cognitive function	Cognitive function determined by standard test batteries	Date of study inclusion (informed consent) to death or end of F/U
Secondary	Exploratory objective	Validation of prognostic 4-miRNA signature-based risk score	Date of study inclusion (informed consent) to death or end of F/U