Health TrialsbyHealthPanel

Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases

ConditionsRadionecrosis of BrainBrain Metastases
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstitut Cancerologie de l'Ouest

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have received the last cranial irradiation with photons or proton therapy for brain metastases ≥ 3 months with one or more sequences;

Age≥18-year-old;

ECOG performance status score ≤ 3

Life expectancy of at least 3 months assessed by graded prognostic score (DS-GPA) score 0.5 or greater;

Disqualifiers

Evidence of active bleeding or a pathological condition at high risk of bleeding: CNS hemorrhage, bleeding diathesis or coagulopathy, hemoptysis (>2.5ml of bright red blood per episode), evidence of history of bowel obstruction, abdominal fistula, or gastrointestinal tract perforation or gastro intestinal abscess occurring less than 28 days prior study entry;

Grade 4 venous thromboelism and peripheral arterial thrombus

Evidence of very high intracranial pressure that suggests brain hernia and needs emergency surgery;

Major surgical procedure or significant traumatic injury less than 28 days prior study entry; minor surgery within 3 days prior to initiation of study treatment;

Trial design

Design model

Parallel

Treatments tested in this trial

  • Bevacizumab

    Drug

    Drug: bevacizumab IV

  • Placebo

    Drug

    Drug: placebo IV

  • Prednisolone

    Drug

    Drug: corticosteroids IV

Treatment groups

84 Participants
are divided into 2 treatment groups
Group A: Experimental armExperimental treatment 2 interventions
Group B: Placebo armPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Efficacy at 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)

Time frame
90 days after start of treatment

Secondary outcomes

1

Patient-reported outcome symptoms of radionecrosis

OveOverall quality of life assessed using the EORTC core quality of life questionnaire (QLQ-C30) and brain module (QLQ-BN20). Evaluations will be conducted in both arms at the following time points: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, and at the End of Treatment visit

Time frame
90 days after start of treatment
2

Toxicity (CTCAE Version 4.0)

Toxicity associated with bevacizumab or placebo and corticosteroids in patients with radionecrosis using CTCAE Version 5.0.

Time frame
up to 90 days after end of treatment

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institut Cancerologie de l'Ouest

Lead sponsor

Source ClinicalTrials.gov
Apply now