Angiotensin II Receptor Blockers, Steroids and Radiotherapy in Glioblastoma

Study Overview
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Brief Summary
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To assess the efficacy of an Angiotensin-II inhibitor (Losartan) to reduce peritumoral edema in newly diagnosed glioblastoma patients.

Detailed Description
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Multicentre, randomized (1:1), double blinded trial:- Arm A: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide ) + Losartan 50mg*2/day until the halting for any reason - Arm B: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide + Placebo 2/day until the halting for any reason.

Official Title
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Angiotensin II Receptor Blockers, Steroids and Radiotherapy in Glioblastoma- A Randomized Multicenter Trial

Conditions
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Newly-diagnosed Glioblastoma

Intervention / Treatment
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* Drug: Losartan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Histologically confirmed glioblastoma (Grade 4 WHO) patients eligible for radiotherapy and concomitant Temozolomide KPS ≥ 50% Adequate hematologic, liver and renal functions Exclusion Criteria: Patients unable to undergo an MRI with contrast Patients without any residual tumor left on the screening MRI of both flair and contrast-enhanced lesions complete surgical resection) Any prior treatment of glioblastoma including any local therapy (immunotherapy, Gliadel wafers, …..) during or after surgical resection Any on-going treatment for high blood pressure at time of inclusion, whatever the therapeutic class of drugs Systolic blood pressure <110 mmHg. relative or definite contra-indication to Losartan: Pregnant or breast feeding women; Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception Non-affiliation to the sécurité sociale

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A: Losartan<br>Arm A: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide ) + Losartan 50mg*2/day until the halting for any reason | Drug: Losartan<br>* Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide ) + Losartan or placebo (Arm A or B) 50mg*2/day until the halting for any reason<br>|
| Placebo Comparator: Arm B: Placebo<br>Arm B: Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide + Placebo 2/day until the halting for any reason | Drug: Placebo<br>* Standard of care (Radiotherapy with concomitant temozolomide followed by monthly cures of temozolomide + Placebo 2/day until the halting for any reason<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steroid dosage required to control brain edema on the last day of radiotherapy in each arm |  | Up to Day 42+ 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steroids dosage 1 month after the end of RT |  | Day 42+ 1 month | 
| Assessment of cerebral edema on MRI |  | Day -28 at -13, Day 42, Day 42+1 month | 
| Tolerance (NCI-CTCAE v3.0) | To be reported according to NCI/CTC version 3.0 (adverse events) | up to day42 +1 month + 7 days | 
| Blood pressure |  | Day -10 at -7, Day0, 42, Day 42+1month | 
| HbA1C |  | Day -10 at -7, D42, Day 42+1month | 
| glycemia |  | Day -10 at -7, Day14, 28, 42, Day 42+1month | 
| body weight |  | Day -10 at -7, Day42, Day 42+1month | 
| side-effects of steroids |  | up to day42 +1 month | 
| Executive functions (  Moca test ) |  | Day-10 at -7, Day 42, Day 42+1 month | 
| Quality of life (EORTC) |  | Day-10 at -7, Day 42, Day 42+1 month | 
| Progression free survival |  | up to 24 months | 
| Overall survival |  | up to 24 months | 
| Survival |  | at 1 year, 2 year | 
| Performance status (KPS) at the end, 1 month , and 2 months after the end of RT |  | at the end, 1 month, and 2 months after the end of RT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Edema, Glioblastoma, Angiotensin-II inhibitors, Losartan, steroids, Radiotherapy, Randomized trial