Hypofractionated Intensity-Modulated Radiation Therapy With Temozolomide and Bevacizumab for Glioblastoma Multiforme
Condition: Glioblastoma Multiforme
MeSH terms: Glioblastoma
Intervention: Bevacizumab; Temozolomide; RT (Radiation Therapy)
Intervention description: Bevacizumab will be administered at 10 mg/kg on day 1 and day 15. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab, patients will receive 6 cycles of Bevacizumab.; Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx) and daily temozolomide at 75 mg/m2 qd concurrent with IMRT. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab, temozolomide will be given at 150-200 mg/m2 qd on days 1-5 of each cycle.; Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx)
Intervention MeSH terms: Bevacizumab; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma; Multiforme

Summary:

      The purpose of this study is to find out whether Hypofractionated Intensity-Modulated
      Radiation Therapy (Hypo-IMRT) combining with temozolomide chemotherapy can be safely given
      with a targeted agent, bevacizumab, and how effective this study treatment will be in
      controlling your brain tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of WHO grade IV primary malignant glioma (GBM or
             gliosarcoma).

          -  Age ≥ 18 years at the time of study registration

          -  Karnofsky Performance Scale ≥ 60%

          -  Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3, hemoglobin ≥ 9.0 g/dl, platelets ≥
             100,000 cells/ mm3

          -  Serum creatinine ≤ 1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) and
             bilirubin ≤ 1.5 times upper limit of normal

          -  Signed informed consent approved by the Institutional Review Board

          -  Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or
             cellulitis, and the underlying cranioplasty must appear intact at the time of study
             entry. Study treatment should be initiated > 28 days following the last surgical
             procedure (including open biopsy, surgical resection, wound revision, or any other
             major surgery involving entry into a body cavity)

        Exclusion Criteria:

          -  Life expectancy of less than 12 weeks

          -  Prior treatment, including radiation therapy or chemotherapy, for GBM with the
             exception of surgery (Gliadel Wafers are allowed at the time of surgery)

          -  Active malignancy, with the exception of superficial basal cell and/or superficial
             squamous (skin) cell, or carcinoma in situ of the cervix

          -  Active infection requiring IV antibiotics

          -  Pregnant or breast feeding

          -  International normalized ratio (INR) > 1.5 and activated partial thromboplastin time
             (aPTT) > 1.5 × the upper limit of normal (ULN) (except for subjects receiving
             anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the
             subject. Therapeutic anticoagulation is permitted

          -  Evidence of ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) v.3 grade 2 CNS
             hemorrhage (CNS hemorrhage when medical intervention indicated), but grade 1 CNS
             hemorrhage (asymptomatic radiographic findings on the baseline brain CT or MRI only)
             is allowed. Punctate hemorrhage or the presence of hemosiderin is not considered a
             Grade 1 event for the purpose of this study. )

          -  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

          -  Current New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  History of myocardial infarction or unstable angina within 6 months prior to
             enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to enrollment

          -  Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to enrollment

          -  History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month
             prior to enrollment

          -  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 enrollment or anticipation of need for major surgical procedure during the
             course of the study

          -  Core needle biopsy or other minor surgical procedure, excluding placement of a
             vascular access device, within 7 days prior to enrollment

          -  History of abdominal fistula or gastrointestinal perforation within 6 months prior to
             enrollment

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria as demonstrated by a Urine protein-creatinine ratios (UPC) ratio ≥ 1.0 at
             screening (Appendix A).

          -  Known hypersensitivity to any component of bevacizumab