Radionecrosis of BrainPhase 3BRADINCT06471465
Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases
A Phase 3 study testing Bevacizumab and Prednisolone in people with Radionecrosis of Brain and Brain Metastases, run by Institut Cancerologie de l'Ouest at 10 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Radionecrosis of Brain, Brain Metastases
- What is being tested?
- Bevacizumab and Prednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 10 sitesFrance
- Study dates
- 29 Apr 2025to Aug 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with a diagnosis of radionecrosis based on a clinical onset of symptoms and radiological findings of RN following radiotherapy, with or without pathological confirmation:
- MRI evidence to support the diagnosis of RN (transient increase in irradiated lesion volume -FLAIR hypersignal and/or enhanced portion- without rCBV increase) COMBINED with nuclear medicine imaging:
- biphasic 18FDG-PET-TDM/MRI according to Horky or 18F-FDOPA with stage 0-1 according to Lizarraga;
- Symptoms are persistent or worsening despite administration of corticosteroids: at least 1 mg/kg/d of prednisolone or equivalent:
- Corticoresistant: neurological symptoms despite administration of at least 2 weeks of 1 mg/kg/d prednisolone or equivalent; Corticodependant: worsening of neurological signs or symptoms after an initial improvement when weaning off steroids at a dose < 0.5 mg/kg/d prednisolone or equivalent;
- Patients must have received the last cranial irradiation with photons or proton therapy for brain metastases ≥ 3 months with one or more sequences;
Show all 21Show fewer
- 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;
- Patient who has never received Bevacizumab for the indication of radionecrosis.
- Adequate organ function:
- Bone marrow function
- Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 Platelet Count ≥ 100,000/mm3, Haemoglobin ≥ 10 g/dL (allowing transfusion or other intervention to achieve this minimum haemoglobin) Coagulation
- International normalized ratio (INR) or prothrombin time < 1.5 × ULN Renal function
- No proteinuria with urine dipstick for proteinuria > 2+
- Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min (measured or calculated using the CDK-EPI formula) Hepatic Function
- Total bilirubin ≤1.5 x the upper limit of normal (ULN)
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN
- Women of childbearing potential must use effective contraceptive measures during the treatment and for 6 months following its cessation;
- Signed informed consent;
- Patient affiliated to a social security scheme.
Who cannot join
- 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;
- Clinically significant cardiovascular disease such as uncontrolled arterial hypertension (BP ≥160 mm Hg or diastolic BP ≥100 mm Hg despite maximal medical therapy), cerebrovascular event, myocardial infarction, cardiac arrhythmias, unstable angina, or congestive heart failure within the last 6 months;
- History of hypertensive crisis or hypertensive encephalopathy
Show all 18Show fewer
- Patients scheduled to undergo head and neck, thoracic, or abdominal radiotherapy during the study treatment
- Prior bevacizumab ≤ 3 months before randomization;
- Progressive brain metastases;
- History of severe allergic anaphylactic reactions to bevacizumab
- Patients with a known hypersensitivity to the active substance or to any of the excipients of bevacizumab are not eligible for participation;
- Patients with a contraindication to the treatment with bevacizumab according to the European SmPC
- Patient pregnant and/or nursing;
- Mental impairment (psychiatric illness/social situations) that may compromise the ability of the patient to give informed consent and comply with the requirements of the study;
- Patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship;
- New cerebral metastasis detected during the inclusion imaging evaluation;
- Prior diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES) with bevacizumab;
- Hypersensitivity known to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
France10 sites, 10 recruiting
- Recruiting
CHRU de Brest
Brest, 29609
Vincent Bourbonne, vincent.boubonne@chu-brest.fr
- Recruiting
Centre Francois Baclesse
Caen, 14000
Dinu Stefan, MD, d.stefan@baclesse.unicancer.fr
- Recruiting
Centre D'Oncologie Et de Radiotherapie 37
Chambray-lès-Tours, 37170
Aurélien Robert, md, a.robert@cort37.fr
- Not yet recruiting
Centre Georges François Leclerc
Dijon, 21079
Julie Vincent, MD, +33 3 80 73 75 00, jvincent@cgfl.fr
- Recruiting
Centre Guillaume le Conquérant
Le Havre, 76600
Paul Lesueur, MD, (33) 2 35 22 21 61, p.lesueur@cglc.fr
- Recruiting
Centre Léon Bérard
Lyon, 69373
Aurélien Maureille, MD, aurelien.maureille@lyon.unicancer.fr
- Recruiting
Centre Eugène marquis
Rennes, 35042
Elodie Vauleon, MD, e.vauleon@rennes.unicancer.fr
- Recruiting
Institut de Cancérologie de l'Ouest
Saint-Herblain, 44805
Mélanie Doré, MD, melanie.dore@ico.unicancer.fr
- Recruiting
Centre Paul Strauss
Strasbourg, 67000
Georges Noel, MD, (33) 3 88 14 18 20, g.noel@icans.eu
- Recruiting
Centre Saint Yves
Vannes, 56000
Osman El Kabbaj, MD, o.elkabbaj@centre-st-yves.fr
About this study
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
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.
Read the detailed description
Brain metastases (BM) are increasingly common in cancer patients; between 10% and 50% (1) will develop BM resulting in potentially disabling symptoms, degrading quality of life and impacting overall survival. The main local treatment options include surgery, hypo-fractionated radiotherapy in stereotactic condition (SRS) and whole brain radiotherapy (WBRT). Over the past decade, SRS has become the most frequently administered focal treatment(2). SRS delivers a single or multi-fraction "ablative" dose as the sole treatment for BM with an overall survival (OS) benefit in patients with single BM (HR = 0.76; CI95%: 0.66 - 0.88)(3) or postoperatively decreasing the risk of recurrence (HR = 0.46; CI95%: 0.24 - 0.88)(4). SRS compared to neurosurgery, has the ability to treat inoperable sites, multiple lesions, and has the advantage of being less invasive. WBRT is now limited to certain patients with multiple BMs and not eligible for SRS. SRS is often preferred to WBRT because of a lower rate of neurocognitive toxicities at 12 months (difference, -34.4%; CI95%: -74.4% to 5.5%; P = .04) for patients with 5 to 10 BMs. Local control at 1 year is high in the order of 90%, and SRS is generally considered a cost-effective treatment.
However, after SRS there can be late side effects, that can start 3 months to several years after irradiation, the most common is cerebral radio necrosis (RN) in 10% of treated patients. The pathophysiology is poorly understood and includes vascular injury, immune-mediated mechanisms and direct neuronal effects. Vascular injury leads to increased permeability after radiotherapy resulting in vasogenic oedema and ischemia, induce hypoxia and an increase in hypoxia inducible factor (HIF-1α) then upregulating vascular endothelial growth factor (VEGF) which exacerbates the oedema by increasing vascular permeability which creates a vicious cycle and RN, hence the importance of inhibiting VEGF(5).
RN may remain as radiological changes (CTCAE v5 grade I toxicity approximately 50%)(6) to be monitored or be symptomatic (grade II-IV) and requiring treatment. Symptoms are usually manifested by focal neurological signs and symptoms related to cerebral oedema. Corticosteroids are the only standard of care before surgery, which is performed when possible. The problem is that high-dose, long-term corticosteroids have multiple side effects and some patients with RN may remain symptomatic despite corticosteroid administration (cortico-resistance) or relapse while decreasing the corticosteroid dose (cortico-dependence) and no standard treatment is available. Only one small (14 patients) randomized double-blind study compared bevacizumab 7.5 mg/kg every 3 weeks versus placebo in RN after irradiation. All 7 patients in the bevacizumab arm had a decrease in FLAIR oedema volume with clinical improvement in contrast to the placebo arm where everything worsened(7).
Thus, the anti-VEGF, bevacizumab, is an option but needs to be validated in a phase 3 randomized trial.
This randomized phase III trial aims to determine whether the impact of adding bevacizumab to standard corticosteroid therapy results in greater symptomatic improvement than corticosteroid therapy alone in patients with symptomatic RN. RN will be defined by a multimodal imaging approach combining brain MRI and nuclear medicine imaging (18F-FDOPA PET or dual phase 18F-FDG PET on CT or MRI). The primary objective of this study is to investigate whether the addition of bevacizumab to standard corticosteroid therapy, compared to corticosteroid therapy plus placebo, results in greater efficacy at 3 months on decrease in corticosteroids and in neurological symptoms associated with radionecrosis (RN). Secondary endpoints were toxicities, quality of life, PROs (Patient Reported Outcomes) and Clinician Reported Outcomes (CRO), imaging changes at 3 months, total weaning of corticosteroids and response duration. An ancillary study will evaluate the correlation between the initial nuclear medicine imaging parameters and the response to treatment as well as the evolution of biological parameters under bevacizumab.
- Conditions
- Radionecrosis of Brain, Brain Metastases
- Being tested
- Bevacizumab, Placebo, Prednisolone
- Keywords
- radionecrosis of brain, brain metastasis, quality of life, bevacizumab
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
Drug: bevacizumab IV
PlaceboDrug
Also called NaCl
Drug: placebo IV
PrednisoloneDrug
Also called Corticosteroids
Drug: corticosteroids IV
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | 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 Receives: Drug: Bevacizumab; Drug: Prednisolone |
| Placebo arm | Placebo comparator | 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 Receives: Drug: Placebo; Drug: Prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 90 days after start of treatment
Secondary outcomes (2)
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
Measured: 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.
Measured: up to 90 days after end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2024
- Study start29 Apr 2025
- Primary completionAug 2028 (estimated)
- Study completionAug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Radionecrosis of BrainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Cancerologie de l'Ouest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luc Ollivier, MD, Principal investigator, Institut de Cancérologie de l'Ouest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06471465
- Sponsor's protocol ID
- ICO-2023-15
- Acronym
- BRADI
- Status last verified
- Jul 2025
- First submitted
- 10 May 2024
- Last updated
- 17 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06471465
- Acronym / sponsor ID
- BRADI / ICO-2023-15
- Conditions
- Radionecrosis of Brain, Brain Metastases
- Keywords
- radionecrosis of brain, brain metastasis, quality of life, bevacizumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Institut Cancerologie de l'OuestUniversity, hospital or other
- Study start
- 29 Apr 2025 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2030 (estimated)
- First posted
- 24 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Brain metastases (BM) are increasingly common in cancer patients; between 10% and 50% (1) will develop BM resulting in potentially disabling symptoms, degrading quality of life and impacting overall survival. The main local treatment options include surgery, hypo-fractionated radiotherapy in stereotactic condition (SRS) and whole brain radiotherapy (WBRT). Over the past decade, SRS has become the most frequently administered focal treatment(2). SRS delivers a single or multi-fraction "ablative" dose as the sole treatment for BM with an overall survival (OS) benefit in patients with single BM (HR = 0.76; CI95%: 0.66 - 0.88)(3) or postoperatively decreasing the risk of recurrence (HR = 0.46; CI95%: 0.24 - 0.88)(4). SRS compared to neurosurgery, has the ability to treat inoperable sites, multiple lesions, and has the advantage of being less invasive. WBRT is now limited to certain patients with multiple BMs and not eligible for SRS. SRS is often preferred to WBRT because of a lower rate of neurocognitive toxicities at 12 months (difference, -34.4%; CI95%: -74.4% to 5.5%; P = .04) for patients with 5 to 10 BMs. Local control at 1 year is high in the order of 90%, and SRS is generally considered a cost-effective treatment.
However, after SRS there can be late side effects, that can start 3 months to several years after irradiation, the most common is cerebral radio necrosis (RN) in 10% of treated patients. The pathophysiology is poorly understood and includes vascular injury, immune-mediated mechanisms and direct neuronal effects. Vascular injury leads to increased permeability after radiotherapy resulting in vasogenic oedema and ischemia, induce hypoxia and an increase in hypoxia inducible factor (HIF-1α) then upregulating vascular endothelial growth factor (VEGF) which exacerbates the oedema by increasing vascular permeability which creates a vicious cycle and RN, hence the importance of inhibiting VEGF(5).
RN may remain as radiological changes (CTCAE v5 grade I toxicity approximately 50%)(6) to be monitored or be symptomatic (grade II-IV) and requiring treatment. Symptoms are usually manifested by focal neurological signs and symptoms related to cerebral oedema. Corticosteroids are the only standard of care before surgery, which is performed when possible. The problem is that high-dose, long-term corticosteroids have multiple side effects and some patients with RN may remain symptomatic despite corticosteroid administration (cortico-resistance) or relapse while decreasing the corticosteroid dose (cortico-dependence) and no standard treatment is available. Only one small (14 patients) randomized double-blind study compared bevacizumab 7.5 mg/kg every 3 weeks versus placebo in RN after irradiation. All 7 patients in the bevacizumab arm had a decrease in FLAIR oedema volume with clinical improvement in contrast to the placebo arm where everything worsened(7).
Thus, the anti-VEGF, bevacizumab, is an option but needs to be validated in a phase 3 randomized trial.
This randomized phase III trial aims to determine whether the impact of adding bevacizumab to standard corticosteroid therapy results in greater symptomatic improvement than corticosteroid therapy alone in patients with symptomatic RN. RN will be defined by a multimodal imaging approach combining brain MRI and nuclear medicine imaging (18F-FDOPA PET or dual phase 18F-FDG PET on CT or MRI). The primary objective of this study is to investigate whether the addition of bevacizumab to standard corticosteroid therapy, compared to corticosteroid therapy plus placebo, results in greater efficacy at 3 months on decrease in corticosteroids and in neurological symptoms associated with radionecrosis (RN). Secondary endpoints were toxicities, quality of life, PROs (Patient Reported Outcomes) and Clinician Reported Outcomes (CRO), imaging changes at 3 months, total weaning of corticosteroids and response duration. An ancillary study will evaluate the correlation between the initial nuclear medicine imaging parameters and the response to treatment as well as the evolution of biological parameters under bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: Bevacizumab, Drug: PrednisoloneExperimental: 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 arm | Placebo comparator | Drug: Placebo, Drug: PrednisolonePlacebo 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patient with a diagnosis of radionecrosis based on a clinical onset of symptoms and radiological findings of RN following radiotherapy, with or without pathological confirmation:
- MRI evidence to support the diagnosis of RN (transient increase in irradiated lesion volume -FLAIR hypersignal and/or enhanced portion- without rCBV increase) COMBINED with nuclear medicine imaging:
- biphasic 18FDG-PET-TDM/MRI according to Horky or 18F-FDOPA with stage 0-1 according to Lizarraga;
- Symptoms are persistent or worsening despite administration of corticosteroids: at least 1 mg/kg/d of prednisolone or equivalent:
- Corticoresistant: neurological symptoms despite administration of at least 2 weeks of 1 mg/kg/d prednisolone or equivalent; Corticodependant: worsening of neurological signs or symptoms after an initial improvement when weaning off steroids at a dose < 0.5 mg/kg/d prednisolone or equivalent;
Key exclusion criteria (18 listed)
- 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;
- Clinically significant cardiovascular disease such as uncontrolled arterial hypertension (BP ≥160 mm Hg or diastolic BP ≥100 mm Hg despite maximal medical therapy), cerebrovascular event, myocardial infarction, cardiac arrhythmias, unstable angina, or congestive heart failure within the last 6 months;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: AvastinDrug: bevacizumab IV | Drug | Experimental arm |
| PlaceboAlso: NaClDrug: placebo IV | Drug | Placebo arm |
| PrednisoloneAlso: CorticosteroidsDrug: corticosteroids IV | Drug | Experimental arm, Placebo arm |
Primary outcome
Efficacy at 90 days on decrease in corticosteroids
Time frame: 90 days after start of treatment
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)
2 secondary outcomes
Patient-reported outcome symptoms of radionecrosis
Time frame: 90 days after start of treatment
Toxicity (CTCAE Version 4.0)
Time frame: up to 90 days after end of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Luc Ollivier, MD principal investigator
Institut de Cancérologie de l'Ouest
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bevacizumab and Prednisolone in people with Radionecrosis of Brain and Brain Metastases, run by Institut Cancerologie de l'Ouest at 10 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Luc Ollivier, MD (02 40 67 99 00 ext. +33, luc.ollivier@ico.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy at 90 days on decrease in corticosteroids (time frame: 90 days after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.