Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases
NCT Number: NCT06471465
Acronym: BRADI
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Radionecrosis of Brain|Brain Metastases
Interventions: DRUG: Bevacizumab|DRUG: Placebo|DRUG: Prednisolone
Sponsor: Institut Cancerologie de l'Ouest
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 84
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-12
Completion Date: 2029-12
Locations: Institut de Cancérologie de l'Ouest, Saint-Herblain, 44805, France

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.

Primary Outcome Measures: Efficacy at 3 months (90 days) on decrease in corticosteroids, To investigate whether the addition of bevacizumab to standard corticosteroid therapy, compared to corticosteroid therapy plus placebo, results in greater efficacy at 3 months (90 days) on decrease in corticosteroids with radionecrosis (RN) after radiotherapy for brain. metastases.

Will be assessed corticosteroids dose at Cycle 1 Day 1 and at 3 months (90 days after Cycle 1 Day 1, End of treatment visit), 90 days after start of treatment|Efficacy at 3 months (90 days) on decrease in corticosteroids, To investigate whether the addition of bevacizumab to standard corticosteroid therapy, compared to corticosteroid therapy plus placebo, results in greater efficacy at 3 months (90 days) on decrease in neurological symptoms associated with radionecrosis (RN) after radiotherapy for brain metastases.

Wil be essassed the decrease of nano scale score at Cycle 1 Day 1 and at 3 months (90 days after Cycle 1 Day , End of treatment visit), 90 days after start of treatment
Secondary Outcome Measures: Patient-reported outcome (symptoms) of radionecrosis, Overall quality-of-life (EORTC core quality of life questionnaire; QLQ-BN20) ; to be assessed in both arm at Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and End of treatment visit, 90 days after start of treatment|Patient-reported outcome (symptoms) of radionecrosis, Overall quality-of-life (EORTC core quality of life questionnaire; QLQ-C30) ; to be assessed in both arm at at Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and End of treatment visit, 90 days after start of treatment|Toxicity (CTCAE Version 4.0), Toxicity associated with bevacizumab or placebo and corticosteroids in patients with radionecrosis using CTCAE Version 5.0., up to 90 days after end of treatment