Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of a new plan for treating glioblastoma. The usual first treatment for glioblastoma is to give focused radiation over 6 weeks in combination with a chemotherapy called temozolomide. In this study the radiation will be given over 2 weeks in combination with temozolomide and another drug, bevacizumab, will also be given. Our idea is that this treatment plan may attack both the tumor and the blood vessels feeding the tumor more effectively. This study will look at what effects, good or bad, this approach has on the patient and the tumor.

Official Title
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A Phase II Study of Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma

Conditions
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Brain Cancer, Malignant Glioma

Intervention / Treatment
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* Other: radiotherapy (RT) in combination with temozolomide and bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic diagnosis of glioblastoma or grade IV glioma. Tumor volume should be less than 60 cc (approximately 5cm maximum diameter). Age > or = to 18 KPS ≥70 Granulocyte count >1.5 X 10 9/L Platelet count >99 X 10 9/L SGOT < 2.5X upper limit of normal (ULN) Serum creatinine < 2X ULN Bilirubin < 2X ULN All patients must sign written informed consent Exclusion Criteria: Any prior chemotherapy, radiotherapy and biologic therapy for glioma. Any prior experimental therapy for glioma. Multicentric glioma Other concurrent active malignancy (with the exception of cervical carcinoma in situ or basal cell ca of the skin). Serious medical or psychiatric illness that would in the opinion of the investigator interfere with the prescribed treatment. Pregnant or breast feeding women. Refusal to use effective contraception Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg) Prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction or unstable angina within 12 months prior to Day 1 History of stroke or transient ischemic attack Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment or anticipation of need for major surgical procedure during the course of the study Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 Serious, non-healing wound, active ulcer, or untreated bone fracture Proteinuria as demonstrated by a UPC ratio ≥ 1.0 at screening Known hypersensitivity to any component of bevacizumab

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RT, with temozolomide and bevacizumab<br>This treatment regimen is novel in that it delivers the initial course of RT over 2 weeks instead of 6 weeks; also, the addition of bevacizumab during and after RT is a new approach. | Other: radiotherapy (RT) in combination with temozolomide and bevacizumab<br>* Bevacizumab10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (Cycle defined as 28 days). Temozolomide 75mg/m2 daily beginning on day 1 through completion of radiotherapy. Hypofractionated dose painting IMRT will start on day 1 and will be delivered on a Monday, Wednesday, Friday schedule for a total of 6 fractions. Post RT therapy: Bevacizumab 10mg/kg IV every two weeks. Temozolomide 150-200mg/m2 daily for 5 consecutive days will be given on 28 day cycles. Follow up: CBC weekly, comprehensive panel and urinalysis monthly, blood pressure every other week. Neurological/physical examination monthly. Gd-enhanced MRI with perfusion every 2 cycles. Neurocognitive testing (approximately 4months post RT, 1 year after diagnosis and then annually in long term survivors). Blood sample for correlative studies monthly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Safety assessments and toxicity grading will follow CTCAE Version 4 Grade | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | through study completion, an average of 1 year | 
| Neurocognitive Outcome |  | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation, BEVACIZUMAB, AVASTIN, TEMOZOLOMIDE, newly diagnosed, Glioblastoma, GBM, malignant glioma, Radiotherapy, 08-126