Avastin/Radiation (XRT)/Temozolomide (Temodar) Followed by Avastin/Temodar/Topotecan for Glioblastoma
Condition: Malignant Glioma; Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Glioma; Gliosarcoma
Intervention: Bevacizumab; Temozolomide; Radiation Therapy (XRT); Topotecan
Intervention description: Bevacizumab (Avastin) at 10 mg/kg every other week during standard radiation therapy (XRT). Following XRT, bevacizumab will remain at 10 mg/kg every other week.; Daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation therapy (XRT). Following XRT, temozolomide will be dosed at 150 mg/m2 daily the first 5 days of each 28-day cycle.; Standard radiation therapy for approximately 6.5 weeks; Following standard radiation therapy, patients will receive topotecan on days 2 through 6 of each 28-day cycle at a dose of 1.5 mg/m2 for patients not taking enzyme-inducing anti-epileptic drugs (EIAEDs) and 2.0 mg/m2 for patients taking EIAEDs.
Intervention MeSH terms: Bevacizumab; Temozolomide; Topotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: malignant glioma; glioblastoma; gliosarcoma; Avastin; bevacizumab; Topotecan; Hycamtin; Temozolomide; Temodar; Pro00019960; Vredenburgh; Duke; Desjardins

Summary:

      This is a phase II study of the combination of radiation therapy, temozolomide and Avastin
      followed by Avastin, temozolomide, and topotecan in grade IV malignant glioma patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of WHO grade IV primary
             malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within
             6 weeks of the last major surgical procedure.

          -  Age > or = to 18 years.

          -  An interval of at least 2 weeks and not > 6 weeks between prior major surgical
             procedure and study enrollment.

          -  No prior radiotherapy or chemotherapy for a brain tumor

          -  Karnofsky > or = to 60%.

          -  Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,500 cells/microliter,
             platelets ≥ 125,000 cells/microliter.

          -  Serum creatinine ≤ 1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) and
             bilirubin ≤ 1.5 times upper limit of normal.

          -  Signed informed consent approved by the Institutional Review Board

          -  If sexually active, patients must agree to use appropriate contraceptive measures for
             the duration of the study and for 6 months afterwards as stated in the informed
             consent.

        Exclusion Criteria:

          -  Pregnancy or breast feeding.

          -  Co-medication that may interfere with study results; e.g. immuno-suppressive agents
             other than corticosteroids.

          -  Active infection requiring IV antibiotics.

          -  Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of
             the grade of the tumor.

          -  Evidence of > grade 1 central nervous system (CNS) hemorrhage on baseline MRI on CT
             scan.

        Avastin-specific Exclusion Criteria:

          -  Inadequately controlled hypertension (defined as systolic blood pressure > 150 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 6 months prior to study
             enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

          -  Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to study enrollment

          -  History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month
             prior to study enrollment

          -  Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic
             anticoagulation)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment 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 study enrollment

          -  History of abdominal fistula, gastrointestinal perforation within 6 months prior to
             study enrollment

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC)
             ratio ≥ 1.0 at screening OR urine dipstick for proteinuria ≥ 2+ (patients discovered
             to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour
             urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

          -  Known hypersensitivity to any component of Avastin

          -  Pregnant (positive pregnancy test) or lactation. Use of effective means of
             contraception (men and women) in subjects of child-bearing potential