Hypofractionated Stereotactic Radiotherapy in Recurrent Glioblastoma Multiforme

Study Overview
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Brief Summary
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Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The treatment comprises maximal safe resection followed by radiotherapy and chemotherapy. Despite appropriate management, 90% of the patients will develop relapse or progression. After progression, the median survival is 5.2 months (Stupp, 2009). The treatment of GBM relapse remains investigational. Reirradiation is an option in selected cases. The objective of this study is to compare 2 schemes of stereotactic hypofractionated radiotherapy in the management of recurrent GBM.

Official Title
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Prospective Randomized Phase II Trial of Hypofractionated Stereotactic Radiotherapy in Recurrent Glioblastoma Multiforme

Conditions
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Recurrent Glioblastoma Multiforme

Intervention / Treatment
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* Radiation: Stereotactic hypofractionated RT 5x5Gy
* Radiation: Stereotactic hypofractionated RT 5x7Gy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older KPS equal or greater than 60 Anatomopathological confirmation of GBM Previous RT with therapeutic doses At least 5 months from the end of RT course Not a candidate to surgical resection Patients with partial resection after resection of recurrent GBM will be allowed Patients with local progression after resection of recurrent GBM will be allowed Lesion with a maximal 150cc volume, as defined by enhancing portion in contrast enhanced MRI Hemoglobin levels (Hb) equal or greater than 10ng/dl. Blood transfusions to correct the Hb will be allowed. Exclusion Criteria: Important comorbidities Concomitant chemotherapy Contraindication to MRI Brainstem glioma

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: Stereotactic hypofractionated RT 5x5Gy<br>Stereotactic hypofractionated radiation therapy delivered as follows: Gross tumor volume (GTV) equals enhancement area in T1 contrast enhanced MRI. Planning tumor volume (PTV) equals GTV plus 3mm margin. the dose of radiation will be 25Gy delivered in 5 fractions.1 fraction per day, non consecutive days in a maximum period of 10 working days. RT to begin in a maximum of 2 weeks after randomization. | Radiation: Stereotactic hypofractionated RT 5x5Gy<br>* Stereotactic hypofractionated radiation therapy delivered as follows: Gross tumor volume (GTV) equals enhancement area in T1 contrast enhanced MRI. Planning tumor volume (PTV) equals GTV plus 3mm margin. The dose of radiation will be 25Gy delivered in 5 fractions.1 fraction per day, non consecutive days in a maximum period of 10 working days. RT to begin in a maximum of 2 weeks after randomization<br>|
| Experimental: Stereotactic hypofractionated RT 5x7Gy<br>Stereotactic hypofractionated radiation therapy delivered as follows: Gross tumor volume (GTV) equals enhancement area in T1 contrast enhanced MRI. Planning tumor volume (PTV) equals GTV plus 3mm margin. the dose of radiation will be 35Gy delivered in 5 fractions.1 fraction per day, non consecutive days in a maximum period of 10 working days. RT to begin in a maximum of 2 weeks after randomization. | Radiation: Stereotactic hypofractionated RT 5x7Gy<br>* Stereotactic hypofractionated radiation therapy delivered as follows: Gross tumor volume (GTV) equals enhancement area in T1 contrast enhanced MRI. Planning tumor volume (PTV) equals GTV plus 3mm margin. The dose of radiation will be 35Gy delivered in 5 fractions.1 fraction per day, non consecutive days in a maximum period of 10 working days. RT to begin in a maximum of 2 weeks after randomization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | progression free survival as defined by the Response Assesment in Neuro Oncology Working Group(Wen, 2010). Briefly progression is defined as: increase in 25% of the product of perpendicular diameters of enhancing lesions significant increase in T2/Flair non enhancing component appearance of new lesions clinical deterioration not atributable to other causes other than the tumor or reduction in corticosteroid dose | from date of randomization until date of first documented progression or death from any cause, which ever comes first, assessed up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | from date of randomization until death from any cause, assessed up to 48 months | 
| local control |  | from date of randomization until date of local progression, assessed up to 48 months | 
| toxicity | toxicity scored by the Common Terminology of Adverse Events version 4 will be assessed every 2 months or in case of patient hospitalization or visit to the E.R. | from date of randomization until death, assessed up to 48 months | 
| quality of life | quality of life measured by the FACT Br questionary will be assessed every 2 months | from date of randomization until last follow-up, assessed up to a period of 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malignant glioma, glioblastoma, radiotherapy, randomized