Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma
Condition: Brain Cancer; Malignant Glioma
MeSH terms: Glioma; Brain Neoplasms
Intervention: radiotherapy (RT) in combination with temozolomide and bevacizumab
Intervention description: 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.
Intervention MeSH terms: Bevacizumab; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Radiation; BEVACIZUMAB; AVASTIN; TEMOZOLOMIDE; newly diagnosed; Glioblastoma; GBM; malignant glioma; Radiotherapy; 08-126

Summary:

      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.
    

Eligibility criteria:

        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