A Study of Subcutaneous Bevacizumab in Relapsed / Progressive Glioblastoma
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: Bevacizumab 25 mg in 1 ml subcutaneously daily
Intervention description: Bevacizumab delivered by subcutaneous injection instead of intravenous infusion.
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GBM; Glioblastoma; Bevacizumab; Avastin; Subcutaneous

Summary:

      STUDY BACKGROUND:

      This research will involve patients with glioblastoma. The drug bevacizumab (Avastin) is FDA
      approved for the treatment of glioblastoma that gets worse after standard therapy. For
      glioblastoma, bevacizumab is given by vein every 14 days. The purpose of this study is to see
      if bevacizumab works as well when it is given as a daily subcutaneous shot as it does when
      given intravenously. A subcutaneous shot is like an insulin shot or a heparin shot. The dose
      of bevacizumab given on this study is in total slightly lower than the FDA approved dose for
      glioblastoma.

      STUDY DESCRIPTION:

      About 10 people will take part in the study. Participants or caregivers will be educated on
      injection and given prefilled syringes to take home. Participants or caregivers will
      administer bevacizumab subcutaneously each day. The bevacizumab will be stored in the
      refrigerator.

      Follow up visits will be weekly for the first 3 weeks, then every 3 weeks. After 18 weeks,
      the follow up interval can be increased to every 6 weeks at the treating physician's
      discretion.

      Participants can keep taking the bevacizumab until:

        -  Tests show that they are not benefiting from it,

        -  The participant has a bad side effect related to study treatment,

        -  The participant can no longer comply with study requirements, or

        -  The participant or doctor feels it is no longer in the participant's best interest.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis: Participants with glioblastoma are eligible for this study. These will
             include

               -  Those with a histologically proven diagnosis of glioblastoma who have developed
                  new changes on MRI following primary treatment.

               -  Those who received primary treatment for a histologically proven lower grade (2
                  or 3) glioma and who now progress with radiographic characteristics of
                  transformed glioma.

          -  Disease status: Patients must have abnormal enhancement on contrast enhanced MRI of
             the brain. They must be patients for whom bevacizumab is indicated and appropriate, as
             drug will be charged to insurance.

               -  Participants with newly detected enhancement are eligible, with bevacizumab
                  treatment hoped to prevent symptoms.

               -  Participants with stable enhancement / edema are eligible if they require
                  corticosteroids to control symptoms, and it is thought bevacizumab treatment
                  might allow lowering of the corticosteroid dose or improvement of symptoms.

          -  Performance status: Eastern Cooperative Oncology Group (ECOG) 0-3.

          -  Age: Greater than 18 years.

          -  Life expectancy: > 3 months.

          -  Prior therapy:

               -  Anti-VEGF treatments: 3 months must have elapsed between any prior anti-VEGF
                  treatment (for example, given as a component of primary treatment) and study
                  participation. These therapies include bevacizumab, cediranib, axitinib,
                  sunitinib as well as other therapeutics targeting VEGF.

               -  Other anti-cancer treatments: Treatments in this category include chemotherapy
                  and targeted therapies not targeting VEGF. 14 days must have elapsed since
                  discontinuation of prior chemotherapeutic treatments for glioma and study
                  treatment.

          -  Radiation: Radiation is integral to the primary treatment of glioma. All participants
             on this study must have had prior radiation to the brain. Radiation must have been
             completed 14 days prior to first study treatment.

          -  Surgery: 14 days must have elapsed since prior major surgery.

          -  Organ function requirements:

               -  Creatinine clearance of 50 or greater.

               -  Absolute neutrophil count of 1500 or greater.

          -  Blood pressure requirements: Participants must have a baseline blood pressure of
             160/90 or less. Participants requiring medicines to control blood pressure are
             eligible.

          -  Informed consent: All patients must sign a written informed consent.

          -  Urine pregnancy test: Women of childbearing age must have a negative urine pregnancy
             test.

        Exclusion Criteria:

          -  People who progress with only nonenhancing tumor on MRI are ineligible. Patients must
             have some component of abnormal enhancement on contrast enhanced MRI of the brain.
             Combinations of nonenhancing and enhancing tumor are eligible.

          -  Pregnancy or breast-feeding: Pregnant or breast-feeding women will not be entered on
             this study.

          -  Renal insufficiency: Patients with a creatinine clearance of less than 50 are
             ineligible.

          -  Proteinuria: Patients with 2+ proteinuria/Moderate or more at baseline are ineligible.

          -  Comorbidities: Patients may not have any baseline comorbidities or laboratory
             abnormalities which would be of grade 3 or worse if graded as toxicities by CTCAE
             (excepting alopecia). An exception is also made for neurologic comorbidities (eg
             ataxia, aphasia) arising as a consequence of the brain tumor; symptoms severe enough
             to warrant medical treatment as is offered on this study are by definition grade 3.

          -  Patients who in the opinion of the investigator may not be able to comply with the
             safety monitoring requirements of the study.

          -  Illness or any other circumstances (as defined by the investigator), which would
             preclude safe performance of study procedures or compromise the ability of the patient
             to consent to study.