Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma

NCT05871021 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 2021-000565-32
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 9

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.

Conditions

Glioblastoma

Keywords

Dose escalation; bevacizumab; VEGF inhibition; FET PET; VMAT

Outcome Measures

Primary Outcomes (1)

• OS

  Overall Survival

  Date of study inclusion (informed consent) to death or end of F/U

Secondary Outcomes (6)

• Safety and tolerability

  Date of study inclusion (informed consent) to death or end of F/U

• PFS-6

  6 months after the date of study inclusion (informed consent)

• PFS

  Date of study inclusion (informed consent) to death or progression

• QoL

  Date of study inclusion (informed consent) to death or end of F/U

• Cognitive function

  Date of study inclusion (informed consent) to death or end of F/U

Study Arms (1)

75 Gy with two cycles of bevacizumab

EXPERIMENTAL

Radiation: Dose escalation of radiation dose beyond the therapeutic standard

Interventions

Dose escalation of radiation dose beyond the therapeutic standard RADIATION

Dose escalation to 75 Gy with concomitant radioprotectant bevacizumab

Also known as: bevacizumab

75 Gy with two cycles of bevacizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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 abdominal or tracheo-oesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrolment
• Serious non-healing wound, ulcer or bone fracture

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (9)

Department of Radiation Oncology, University Hospital Augsburg

Augsburg, Germany

Location

Department of Radiation Oncology, University Hospital Köln

Cologne, Germany

Location

Department of Radiation Oncology, University Hospital Frankfurt

Frankfurt, Germany

Location

Department of Radiation Oncology, University Hospital Freiburg

Freiburg im Breisgau, Germany

Location

Department of Radiation Oncology, University Hospital Leipzig

Leipzig, Germany

Location

Department of Radiation Oncology, Medical Faculty Mannheim

Mannheim, Germany

Location

Department of Radiation Oncology, University Hospital, LMU Munich

Munich, Germany

Location

Department of Neurology, University Hospital Regensburg

Regensburg, Germany

Location

Department of Radiation Oncology

Tübingen, 72076, Germany

Location

Related Publications (1)

• Maier SH, Schonecker S, Anagnostatou V, Garny S, Nitschmann A, Fleischmann DF, Buttner M, Kaul D, Imhoff D, Fokas E, Seidel C, Hau P, Kolbl O, Popp I, Grosu AL, Haussmann J, Budach W, Celik E, Kahl KH, Hoffmann E, Tabatabai G, Paulsen F, Holzgreve A, Albert NL, Mansmann U, Corradini S, Belka C, Niyazi M, Bodensohn R. Dummy run for planning of isotoxic dose-escalated radiation therapy for glioblastoma used in the PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06). Clin Transl Radiat Oncol. 2024 May 4;47:100790. doi: 10.1016/j.ctro.2024.100790. eCollection 2024 Jul.

  PMID: 38765202 DERIVED

Related Links

• Dosimetric feasibility analysis and presentation of an isotoxic dose-escalated radiation therapy concept for glioblastoma used in the PRIDE trial
• Dummy run for planning of isotoxic dose-escalated radiation therapy for glioblastoma used in the PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06)
• FET PET-based target volume delineation for the radiotherapy of glioblastoma: A pictorial guide to help overcome methodological pitfalls

MeSH Terms

Conditions

Glioblastoma

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Maximilian Niyazi, Prof. Dr.

  University Hospital Tuebingen, Department of Radiation Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2023
• First Posted: May 23, 2023
• Study Start: April 10, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): April 15, 2029
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9)