Exploratory Study of the Modulation of the Immune System by VEGF Blockade in Patients With Glioblastoma Multiforme (GBM)

Study Overview
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Brief Summary
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Blood samples will be obtained from newly diagnosed GBM patients treated with combined radiotherapy (RT), temozolomide (TMZ) and bevacizumab (BEV) at specific time points. The primary outcome is the shift in T reg cell fraction a defined by determining the proportion of CD4 cells that are CD4+ CD25.

Detailed Description
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Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor and it remains a lethal disease. Approximately 4 weeks post surgery for tumor resection, patients will proceed to standard of care treatment which currently consists of temozolomide (TMZ) with concurrent radiation therapy (RT) for 6 weeks. This study will add bevacizumab (BEV) to the standard of care regimen in newly diagnosed patients. The Bevacizumab will be added 2 weeks post start of RT/TMZ. Administration of bevacizumab will continue concurrently with TMZ every 2 weeks for 12 months. Blood samples will be obtained from these patients at 3 different time points during this study.

Official Title
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DMS 0947 Exploratory Study of the Modulation of the Immune System by Vascular Endothelial Growth Factor (VEGF) Blockade in Patients With Glioblastoma Multiforme (GBM)

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven GBM Karnofsky status equal to or greater than 60% Exclusion Criteria: Inadequately controlled hypertension Prior history of hypertension crisis or hypertensive encephalopathy History of stroke or transient ischemic attach within 12 months

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab<br>Bevacizumab + temozolomide + radiotherapy followed by adjuvant bevacizumab + temozolomide | Drug: Bevacizumab<br>* Bevacizumab every 2 weeks 10mg/kg beginning 2 weeks after start of Radiation Therapy<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the peripheral blood T-reg profile between pretreatment and 4 weeks after completion of treatment with the addition of bevacizumab to RT and TMZ in patients with glioblastoma |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic shift in the phenotypic T cell, B cell, NK cell and DC repertoire induced by RT-TMZ-BEV comparing pretreatment and 4 weeks after completion of treatment |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GBM, Grade IV, glioma