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CASE 4309   |   CC845
Phase I/II Trial of Radiosurgery Plus Bevacizumab in Patients with Recurrent / Progressive Glioblastoma

Main Campus
Phase 1
Phase 2

Contact Information
Cancer Answer Line


8:00 am - 4:30 pm, Monday - Friday

  1. Primary:
    • To determine the maximum tolerated dose of radiosurgery used to treat recurrent/progressive GBM concurrently with bevacizumab.
    • To determine the overall survival of patients with recurrent/progressive GBM treated with bevacizumab and radiosurgery.
  2. Secondary:
    • To evaluate the toxicities of the combination of bevacizumab and radiosurgery.
    • To evaluate the progression-free survival of patients treated with bevacizumab and radiosurgery.

Inclusion Criteria
  1. Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV) at primary or subsequent resection.
  2. Completed standard concurrent conventional fractionated radiotherapy plus daily temozolomide (75 mg/m2/day)
  3. Radiographic evidence of tumor recurrence/progression as defined by a contrast enhanced MRI at least 3 months after the completion of radiation therapy
  4. Unifocal enhancing disease. The enhancing focus must be <= 3 cm in maximum diameter.
  5. History/physical examination within 14 days prior to registration;
  6. The patient must have recovered from the effects of prior therapy before study entry. The patient must not have received chemotherapy within the following time frames: Non-cytotoxic agents: 2 weeks Cytotoxic agents: 3 weeks Nitrosoureas: 6 weeks
  7. Must be able to undergo MRI imaging.
  8. Documentation of steroid doses within 14 days prior to registration.
  9. Karnofsky performance status > 60;
  10. Age ≥ 18;
  11. CBC obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:
    • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
    • Platelets ≥ 100,000 cells/mm3;
    • Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.);
  12. Adequate renal function, as defined below:
    • BUN ≤ 30 mg/dl within 14 days prior to study entry.
    • Creatinine ≤ 1.7 mg/dl within 14 days prior to study entry.
    • Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio. For UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg.
  13. Adequate hepatic function, as defined below:
    • Bilirubin ≤ 2.0 mg/dl within 14 days prior to study entry
    • ALT/AST ≤ 3 x normal range within 14 days prior to study entry
  14. Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior study entry
  15. Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study entry.
    • Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:
      • No active bleeding or pathological condition that carries a high risk of bleeding e.g., tumor involving major vessels or known varices)
      • In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
  16. Patient must provide study specific informed consent prior to study entry.
  17. Women of childbearing potential and male participants must practice adequate contraception.
  18. For females of child-bearing potential, negative serum pregnancy test within 14 days prior to entry

Exclusion Criteria
  1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible).
  2. More than one focus of enhancement
  3. Involvement of the brainstem (defined as the midbrain or lower), or proximity to the optic chiasm/optic nerves requiring radiosurgery dose reduction.
  4. Prior use of chemotherapy wafers or any other intratumoral or intracavitary treatment are not permitted. Prior radiosurgery is not permitted.
  5. Prior treatment with intravenous bevacizumab
  6. Severe, active co-morbidity, defined as follows:
    • Unstable angina and/or congestive heart failure within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Evidence of recent myocardial infarction or ischemia by the findings of ST elevations of ≥ 2 mm using the analysis of an EKG performed within 14 days of entry
    • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration
    • History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
    • Serious and inadequately controlled cardiac arrhythmia
    • Uncontrolled hypertension
    • Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
    • Evidence of bleeding diathesis or coagulopathy
    • Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection.
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of entry
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of entry
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
    • Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
    • Active connective tissue disorders, such as lupus or scleroderma that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
    • Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
  7. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  8. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug.
  9. Patients treated on any other therapeutic clinical trials within 30 days prior to study entry or during participation in the study.

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