Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme
Condition: Glioblastoma Multiforme; Glioblastoma - Category
MeSH terms: Glioblastoma
Intervention: Bevacizumab; Magnetic Resonance Spectroscopy (MRS); Border Zone Stereotactic Radiosurgery (BZ-SRS)
Intervention description: Patients will receive bevacizumab (10 mg/kg) one day before and then at day 14 followed by10 mg/kg/day every 14 days until progression.; Subjects will have MRS prior to BZ-SRS.; The 'border zone' of the tumor will be targeted by SRS in a single session.
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Border Zone Stereotactic Radiosurgery; Bevacizumab; Recurrent Glioblastoma Multiforme; Progressive Glioblastoma Multiforme; Magnetic Resonance Spectroscopy; Glioblastoma; Brain Cancer; Brain Tumor; Radiosurgery

Summary:

      This is a phase II study on the usage of stereotactic Gamma Knife radiosurgery as a boost to
      the tumor bed border zone in conjunction with the usage of bevacizumab.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed glioblastoma multiforme, WHO grade IV astrocytoma.

          2. Prior first-line treatment with surgery or biopsy followed by fractionated
             radiotherapy with concurrent temozolomide-containing chemotherapy is required for
             glioblastoma patients. Additional prior chemotherapy is allowed, without limitation on
             number of recurrences.

          3. An interval of at least 2 months since completion of fractionated radiotherapy.

          4. Age > 18 years

          5. Life expectancy of at least 12 weeks.

          6. Karnofsky Performance Status score (KPS) of ≥ 60

          7. Documented recurrent disease; Disease must be evaluable, but does not need to be
             measurable; the target site for SRS does not need to be located in a
             previously-irradiated area.

          8. All patients must have no restrictions to obtaining MRI with and without gadolinium
             contrast.

          9. Adequate bone marrow, hepatic and renal function ; BUN < 25 and Cr < 1.7

         10. Negative pregnancy test at the time of SRS in any patient who could be pregnant.

         11. Willingness to forego additional therapy until evidence of disease progression

        Exclusion Criteria:

        1. General Medical Exclusions:

          1. Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study.

          2. Active malignancy, other than superficial basal cell and superficial squamous (skin)
             cell, or carcinoma in situ of the cervix within last 3 years.

          3. Prior radiosurgery

          4. Prior intracavitary irradiation or Gliadel wafers.

        2. Disease-Specific Exclusions:

          1. Inability to comply with protocol or study procedures

          2. Prior treatment with bevacizumab.

          3. Inability to undergo MRI with and without contrast administration.

        3. Bevacizumab-Specific Exclusions:

          1. Inadequately controlled hypertension.

          2. Prior history of hypertensive crisis or hypertensive encephalopathy.

          3. New York Heart Association (NYHA) Grade II or greater congestive heart failure.

          4. History of myocardial infarction or unstable angina within 6 months prior to Day 1.

          5. History of stroke or transient ischemic attack within 6 months prior to Day 1.

          6. Significant vascular disease within 6 months prior to Day 1.

          7. History of hemoptysis within 1 month prior to Day 1.

          8. Evidence of bleeding diathesis or significant coagulopathy

          9. Major surgical procedure, open biopsy, or significant traumatic injury within 14 days
             prior to Day 1 or anticipation of need for major non -cranial surgical procedure
             during the course of the study.

         10. Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to Day 1.

         11. History of abdominal fistula or gastrointestinal perforation within 6 months prior to
             Day 1.

         12. Serious, non-healing wound, active ulcer, or untreated bone fracture.

         13. Proteinuria

         14. Known hypersensitivity to any component of bevacizumab

         15. Pregnancy (positive pregnancy test) or lactation. Use of effective means of
             contraception (men and women) in subjects of child-bearing potential.