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RECRUITING
NCT06471465
PHASE3

Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases

Sponsor: Institut Cancerologie de l'Ouest

View on ClinicalTrials.gov

Summary

Brain metastases (BM) afflict a significant portion of cancer patients, ranging from 10% to 50%, leading to debilitating symptoms and diminished quality of life, thereby impacting overall survival. Treatment options typically include surgery, stereotactic radiosurgery (SRS), and whole brain radiotherapy (WBRT). SRS has emerged as the preferred focal treatment due to its efficacy, delivering ablative doses with notable overall survival benefits, especially for single BM or postoperative cases, while being less invasive than neurosurgery and capable of addressing inoperable sites and multiple lesions. Contrastingly, WBRT is now reserved for select cases with multiple BMs ineligible for SRS, owing to its lower rate of neurocognitive toxicities and high local control rates at one year. Despite its advantages, SRS can engender late side effects, with cerebral radio necrosis (RN) being the most common, occurring in approximately 10% of patients treated. The exact pathophysiology of RN remains unclear but is thought to involve vascular injury, immune-mediated mechanisms, and direct neuronal effects, culminating in radiological changes or symptomatic manifestations necessitating treatment. Corticosteroids are the mainstay therapy, albeit with associated side effects and instances of cortico-resistance or cortico-dependence. Bevacizumab, an anti-VEGF agent, has shown promise in small studies but awaits validation in larger trials. Consequently, a randomized phase III trial seeks to evaluate the efficacy of adding bevacizumab to standard corticosteroid therapy in patients with symptomatic RN. The trial aims to determine if this combination therapy yields superior symptomatic improvement compared to corticosteroids alone. RN will be diagnosed using multimodal imaging, and the primary objective is to assess the efficacy of bevacizumab in reducing corticosteroid usage and neurological symptoms associated with RN at three months. Secondary endpoints include toxicities, quality of life, imaging changes, and response duration. Additionally, an ancillary study will explore correlations between initial imaging parameters and treatment response, as well as changes in biological parameters with bevacizumab therapy.

Official title: Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases: a Multicentre Randomized, Controlled Double-blind Phase III Study, Comparing Bevacizumab Versus Placebo

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

84

Start Date

2025-04-29

Completion Date

2030-08

Last Updated

2025-08-17

Healthy Volunteers

No

Interventions

DRUG

Bevacizumab

Drug: bevacizumab IV

DRUG

Placebo

Drug: placebo IV

DRUG

Prednisolone

Drug: corticosteroids IV

Locations (10)

CHRU de Brest

Brest, France

Centre Francois Baclesse

Caen, France

Centre D'Oncologie Et de Radiotherapie 37

Chambray-lès-Tours, France

Centre Georges François Leclerc

Dijon, France

Centre Guillaume le Conquérant

Le Havre, France

Centre Léon Bérard

Lyon, France

Centre Eugène marquis

Rennes, France

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

Centre Paul Strauss

Strasbourg, France

Centre Saint Yves

Vannes, France