Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05871021

Studienbeginn:
April 2024

Letztes Update:
16.04.2024

Wirkstoff:
-

Indikation (Clinical Trials):
Glioblastoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Ludwig-Maximilians - University of Munich

Collaborator:
-

Studienleiter

Maximilian Niyazi, Prof. Dr.
Principal Investigator
University Hospital, LMU Munich

Kontakt

Ulrike Plugradt
Kontakt:
Phone: 004989440074770
E-Mail: Ulrike.Pflugradt@med.uni-muenchen.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Department of Radiation Oncology
81377 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Maximilian Niyazi, Prof.» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. OS (Time Frame - Date of study inclusion (informed consent) to death or end of F/U):
Overall Survival

Secondary outcome:

1. Safety and tolerability (Time Frame - 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

2. PFS-6 (Time Frame - 6 months after the date of study inclusion (informed consent)):
6 months rate of progression-free survival

3. PFS (Time Frame - Date of study inclusion (informed consent) to death or progression):
Progression-free survival

4. QoL (Time Frame - 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

5. Cognitive function (Time Frame - Date of study inclusion (informed consent) to death or end of F/U):
Cognitive function determined by standard test batteries

6. Exploratory objective (Time Frame - Date of study inclusion (informed consent) to death or end of F/U):
Validation of prognostic 4-miRNA signature-based risk score

Geprüfte Regime

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

Quelle: ClinicalTrials.gov

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