Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases

Sponsor
Institut Cancerologie de l'Ouest
Study ID
NCT06471465
Phase
PHASE3
Status
Recruiting
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Conditions

  • Brain Metastases
  • Radionecrosis of Brain

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Bevacizumab — DRUG
    Drug: bevacizumab IV
  • Placebo — DRUG
    Drug: placebo IV
  • Prednisolone — DRUG
    Drug: corticosteroids IV

Study Details

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.

Key Dates

First listed
Jun 24, 2024
Start date
Apr 29, 2025
Status verified
Jul 2025
Primary completion
Aug 31, 2028
Completion
Aug 31, 2030

Study Design

Enrollment
84 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental arm
    Experimental: bevacizumab + prednisolone The patient will receive bevacizumab 7.5 mg/kg IV given on Q3W for4 cycles or until progression of radionecrosis or unacceptable adverse event. Once the patient has started the study treatment, the dose of prednisolone will be tapered every 7 days beginning at C2D1 (at least 10 mg prednisolone or equivalent), depending on tolerance. If the patient weighs more than 100 kg, the tapering can be increased by 10 to 20 mg per week for the first 3 months. Interventions: Drug: bevacizumab Drug : prednisolone
  • Placebo Comparator: Placebo arm
    Placebo arm: placebo + prednisolone The patient will receive placebo 0.9% NaCl volume equal to bevacizumab volume added to 100 mL bag of 0.9% NaCl delivered IV given on on Q3W for4 cycles or until progression of radionecrosis or unacceptable adverse event. Once the patient has started the study treatment, the dose of prednisolone will be tapered every 7 days beginning at C2D1 (at least 10 mg prednisolone or equivalent), depending on tolerance. If the patient weighs more than 100 kg, the tapering can be increased by 10 to 20 mg per week for the first 3 months. Interventions: Drug: placebo Drug : prednisolone

Primary Outcome Measure

Efficacy at 90 days on decrease in corticosteroids [ Time Frame: 90 days after start of treatment ]

Central Contacts

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