Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma
Condition: Glioma
MeSH terms: Glioma
Intervention: bevacizumab; carmustine
Intervention description: Bevacizumab (10 mg/kg) will be given intravenously every other week starting one week before the first dose of BCNU. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.; BCNU (200 mg/m2), will be given over 4 hours as a continuous intravenous infusion every 8 weeks. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.
Intervention MeSH terms: Bevacizumab; Carmustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult anaplastic astrocytoma; adult glioblastoma; adult gliosarcoma; adult giant cell glioblastoma; adult anaplastic oligodendroglioma; adult mixed glioma; recurrent adult brain tumor

Summary:

      RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the
      growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such
      as carmustine, work in different ways to stop the growth of tumor cells, either by killing
      the cells or by stopping them from dividing. Giving bevacizumab together with carmustine may
      kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving bevacizumab together with carmustine
      works in treating patients with relapsed or progressive high-grade glioma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed GBM, anaplastic astrocytoma, anaplastic oligoastrocytoma or
             anaplastic oligodendroglioma.

          -  Disease progression (confirmed by MRI, PET or both) after radiation therapy

          -  At least 28 days have elapsed since chemotherapy, major surgery or radiation therapy.

          -  No other malignancy within 3 years except for non-melanomatous skin cancer or in situ
             cervical cancer.

          -  Karnofsky performance score at least 70

          -  Platelet count ≥ 130/mm3.

          -  Absolute neutrophil count ≥ 1500/mm3

          -  Calculated creatinine clearance greater than 45 mg/dl

          -  AST < 2 times the upper limit of normal

          -  Bilirubin < 1.5 times the upper limit of normal

          -  Ability to give signed informed consent

          -  Patients must be 18 years of age or older.

        Exclusion Criteria:

          -  Prior intravenous or oral nitrosoureas (BCNU, CCNU) or prior VEGF targeted therapy
             including bevacizumab. No more than two prior chemotherapy regimens are allowed. Prior
             or current steroid use is allowed.

          -  Evidence of CNS hemorrhage

          -  Requirement for therapeutic anticoagulation

          -  Any grade 3 or greater hemorrhage within the previous 28 days

          -  Active inflammatory bowel disease

          -  Inadequately controlled hypertension

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association 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

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  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, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Proteinuria at screening

          -  Pregnant (or lactating). Use of effective means of contraception in subjects of
             child-bearing potential

          -  Prior organ transplantation

          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  Known acquired immune deficiency syndrome (AIDS) or HIV positive status