Concomitant Association of Ultrafractionated Brain Irradiation - Temozolomide in Inoperable Primary Glioblastoma Multiforme

Study Overview
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Brief Summary
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The main purpose of this study is the evaluation of concomitant association of ultrafractionated irradiation and Temodal® in patients with inoperable primary glioblastoma multiforme; study of tolerance and objective response rate. The secondary purposes of this study are the evaluation of progression free survival, global survival and tolerance through toxicity study. The therapeutic response according to methylation or not of MGMT is also evaluated.

Official Title
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Phase II Clinical Trial of Concomitant Association of Ultrafractionated Brain Irradiation - Temozolomide in Inoperable Primary Glioblastoma Multiforme

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Radiation: Ultrafractionated brain irradiation
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: giving their informed consent having a supratentorial malignant glioma, either grade 4 of St. Anne/Mayo grading, or glioblastoma multiforme according to WHO classification having an inoperable brain tumor (diagnosed by stereotactic biopsy) having a general status, evaluated by Karnofsky scale, >60 having a life expectancy >3 months not having previously had a brain irradiation and/or adjuvant or neo-adjuvant chemotherapy potentially having another cancer, if histology and clinical history are available for comparison being able to take oral tablets no HIV disease satisfactory hematology, hepatic and renal functions: polymorphonuclear neutrophils >1500/mm3, platelets >100000/mm3, Hb >8g/dl, creatinemia ≤1.5 times upper normal value, total bilirubin <1.5 times upper normal value, ASAT and ALAT <3 times upper normal value for women of childbearing potential, a contraception is given Exclusion Criteria: having an under tentorial malignant glioma (brain stem and/or cerebellum), grade 4 of St. Anne/Mayo grading having a Karnofsky score <60 having a life expectancy <3 months having had a brain irradiation or an adjuvant or neoadjuvant chemotherapy refusing any additional therapy having a non-malignant but serious systemic disease or uncontrolled active infection having a severe psychiatric disorder not having signed the informed consent pregnant or breastfeeding woman

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ultrafractionated brain irradiation - temozolomide<br> | Radiation: Ultrafractionated brain irradiation<br>* 0.75 Gy a day, 5 times a week, for 6 weeks (total dose: 67.5 Gy)<br>Drug: Temozolomide<br>* 75 mg/m2/day, 7 times a week, for 6 weeks (total 42 days)<br>* Other names: Temodal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete response | defined as total regression of tumor area contrast in MRI, with stability or amelioration of neurological status of patient without corticoids | through study completion, 2 years | 
| partial response | defined by at least 50% diminution of tumor size, evaluated by the product of 2 perpendicular diameters measured by MRI, with stability or amelioration of neurological status of patient receiving stable or reduced corticoid doses | through study completion, 2 years | 
| stabilization | corresponding to at least 50% diminution of tumor size in MRI, with stability of neurological status of patient receiving steady corticoid doses | through study completion, 2 years | 
| progression | defined by increase of at least 25% of tumor size and/or a second brain localization in MRI, with degradation of neurological status of patient | through study completion, 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| global survival |  | through study completion, 2 years | 
| treatment tolerance | evaluated by general, neurological and hematological status, according to National Cancer Institute-Common toxicity criteria (NCI-CTC) | through study completion, 2 years | 
| survival without tumor recurrence | tumor recurrence detected with radiology examination | through study completion, 2 years | 
| life quality | evaluated with European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ - C30) | through study completion, 2 years |