Dose Escalation Radiotherapy With Modulation of Intensity and Integrated Boost (SIB-IMRT) in the Treatment of Glioblastomas in Adults

Study Overview
=================
Brief Summary
-----------------
The main goal of this study is to evaluate and to determine the dose of a highly accurate irradiation (allowing to increase the dose delivered while restricting the risk of complication) in association with temozolomide.

Official Title
-----------------
Dose Escalation Radiotherapy With Modulation of Intensity and Integrated Boost in Association With a Temozolomide in the Treatment of Glioblastoma

Conditions
-----------------
Glioblastoma

Intervention / Treatment
-----------------
* Radiation: radiotherapy
* Drug: temozolomide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histopathologically proven diagnosis of glioblastoma (WHO grade IV astrocytoma) Diagnosis must be obtained by a stereotactic or surgical biopsy Age between 18 and 70 Total or partial surgical resection deemed as not possible by a neurosurgeon OMS performance status 0 or 1 Adequate blood function : absolute neutrophil count > 1.5 x 109/L, platelets count > 100 x 109/L platelets; Adequate liver function: bilirubin < 1.5 ULN (upper limit of normal), ALT and AST < 3 ULN, Adequate renal function: creatinine < 1.5 ULN Patient must have been informed and must have signed the specific informed consent form. Exclusion Criteria: other malignancy histology resection of the brain tumor complete on MRI exploration patient unable to give informed consent patient presenting counter-indication to MRI exploration patient must not have received neither radiotherapy nor chemotherapy for that affection concomitant malignancy patient already enrolled in another biomedical study with an experimental molecule pregnant, nursing woman, or without contraception private individuals of freedom or under tutelage (including legal guardianship) psychiatric, behavioural disorders or geographical situation precluding the administration or follow-up of the protocol (including claustrophobia)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: radiotherapy + temozolomide<br>Radiotherapy: dose given at PTV-g will be 70 Gy/28 fractions level 1 75 Gy/30 fractions level 2 80 Gy/32 fractions level 3 dose given at PTV-a will be 56 Gy/28 fractions level 1 60 Gy/30 fractions level 2 60.8 Gy/32 fractions level 3 Chemotherapy: temozolomide given at the dose of 75mg/m2 | Radiation: radiotherapy<br>* patients will receive from 6 to 7 weeks 5 days a week radiations. The dose of radiation will depend on the level they will be included.<br>Drug: temozolomide<br>* patient will receive whatever the level 7 days a week, temozolomide at the dose of 75mg/m2 during radiotherapy period. They will then follow one month after the end the radiochemotherapy an adjuvant treatment corresponding to a 5 days treatments of temozolomide at the dose of 200mg/m2 every 28 days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the OTR (optimal tolerated regimen) of radiotherapy administered in combination with temozolomide as first-line therapy in patients with de novo glioblastoma |  | 3 months after the start of the radiotherapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IMRT, Radiotherapy escalation dose, glioblastoma, escalation radiotherapy dose