Bevacizumab and Irinotecan to Treat Brain Tumors
Condition: High-Grade Gliomas
MeSH terms: Glioma
Intervention: Bevacizumab; Irinotecan hydrochloride
Intervention description: 10 mg/kg intravenous injection; 125 mg/m^2 if patient is on a non-enzyme inducing anti-epileptic drugs 340 mg/m^2 if patient is on enzyme inducing anti-epileptic drugs every two weeks on a 4 week cycle
Intervention MeSH terms: Bevacizumab; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Brain Tumor; Chemotherapy; Progression; Radiotherapy; Antiangiogenesis; Glioma

Summary:

      Background:

        -  Bevacizumab is a genetically engineered antibody that blocks the growth of new blood
           vessels in tumors. It has shown activity against human brain tumors in laboratory tests
           and human clinical trials.

        -  Irinotecan causes damage to the deoxyribonucleic acid (DNA) in cancer cells so that the
           cells cannot reproduce or repair themselves. It is approved for treating patients with
           colorectal cancer.

        -  Bevacizumab and irinotecan in combination are more effective against colon cancer than
           either drug alone.

      Objectives:

        -  To determine the safety of bevacizumab and irinotecan and any side effects associated
           with the combination of the two drugs when given to patients with high grade gliomas.

        -  To determine if the combination of bevacizumab and irinotecan can help patients with
           brain tumors that have grown after treatment with bevacizumab alone.

      Eligibility:

      -Patients 18 years of age and older who have been treated on National Cancer Institute (NCI)
      trial 06-C-0064 (NCT00271609), "Bevacizumab Alone for Recurrent Gliomas," and whose tumor has
      progressed.

      Design:

      Participants receive infusions of bevacizumab and irinotecan through a vein once every 2
      weeks in 4-week treatment cycles, plus the following procedures:

        -  History, physical and neurological examinations every 2 weeks for the first treatment
           cycle and then every 4 weeks

        -  Magnetic Resonance Imaging (MRI) scan of the head every 4 weeks.

        -  Routine lab every week.

        -  Quality-of-life questionnaire every 4 weeks
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Patients must have been treated on the National Cancer Institute (NCI) trial 06-C-0064
        (NCT00271609); bevacizumab alone for recurrent gliomas and now have evidence for tumor
        progression by magnetic resonance imaging (MRI) scan.

        Patients with histologically proven intracranial malignant glioma will be eligible for this
        protocol. Malignant glioma include glioblastoma multiforme (GBM), gliosarcoma, anaplastic
        astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma
        (AMO), or malignant astrocytoma NOS (not otherwise specified).

        Patients must have evidence for tumor progression by MRI or computed tomography (CT) scan.
        This scan should be performed within 14 days prior to registration and on a fixed dose of
        steroids for at least 5 days. If the steroid dose is increased between the date of imaging
        and registration a new baseline magnetic resonance (MR)/CT is required. The same type of
        scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor
        measurement.

        Patients must be greater than or equal to 18 years old, and with a life expectancy greater
        than 8 weeks.

        All patients or their previously designated durable power of attorney (DPA) (if the patient
        is deemed by the treating physician to be impaired or questionably impaired in such a way
        that the ability of the patient to give informed consent is questionable) must sign an
        informed consent indicating that they are aware of the investigational nature of this
        study.

        Patients must have a Karnofsky performance status of greater than or equal to 60.

        Patients must not be more than 4 weeks since their last bevacizumab treatment and may have
        received no form of treatment (i.e. radiation, chemotherapy, surgery, investigational
        therapy) for their progressive tumor between their last bevacizumab treatment and
        enrollment of this companion trial.

        Patients must have adequate bone marrow function (white blood cell (WBC) greater than or
        equal 3,000/microl, absolute neutrophil count (ANC) greater than or equal to1,500/mm^3,
        platelet count of greater than to or equal 100,000/mm^3), and hemoglobin greater than or
        equal to 10 gm/dl), adequate liver function (serum glutamic oxaloacetic transaminase (SGOT)
        and bilirubin less than 2.5 times upper limits of normal (ULN)), and adequate renal
        function (creatinine less than 1.5 mg/dL and/or creatinine clearance greater than or equal
        to 60 cc/min) before starting therapy. These tests must be performed within 14 days prior
        to registration. Eligibility level for hemoglobin may be reached by transfusion.

        Patients must not have any significant medical illnesses that in the investigator's opinion
        cannot be adequately controlled with appropriate therapy or would compromise the patients'
        ability to tolerate this therapy.

        This study was designed to include women and minorities, but was not designed to measure
        differences of intervention effects. Males and females will be recruited with no preference
        to gender. No exclusion to this study will be based on race.

        Urine protein should be screened by dipstick or urine analysis for Urine Protein Creatinine
        (UPC) ratio. For proteinuria greater than or equal to 1+ or urine protein:creatinine UPC
        ratio greater than 1.0, 24-hour urine protein should be obtained and the level should be
        less than 1000 mg for patient enrollment.

        Subjects must be willing and able to practice adequate contraception.

        EXCLUSION CRITERIA:

        Concurrent use of other standard chemotherapeutics or investigative agents.

        Patients who have an active infection.

        Pregnant (positive pregnancy test) or nursing women. Both fertile men and women must agree
        to use adequate contraceptive measures during study therapy and for at least 6 months after
        the completion of bevacizumab therapy.

        Concurrent anti-coagulation or anti-platelet medication (including aspirin, non-steroidal
        anti-inflammatories, cyclooxygenase-2 (COX-2) inhibitors).

        Serious or non-healing wound, ulcer or bone fracture.

        History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
        within 28 days.

        Invasive procedures defined as follows:

          -  Major surgical procedure, open biopsy or significant traumatic injury within 28 days
             prior to Day 1 therapy

          -  Anticipation of need for major surgical procedures during the course of the study

          -  Core biopsy within 7 days prior to day (D)1 therapy

        Patients with clinically significant cardiovascular disease:

          -  History of cerebrovascular accident (CVA) within 6 months

          -  Uncontrolled hypertension (greater than 150/100 mmHg)

          -  Myocardial infarction or unstable angina within 6 months

          -  New York heart association grade II or greater congestive heart failure

          -  Serious cardiac arrhythmia requiring medication

          -  Unstable angina pectoris

          -  Clinically significant peripheral vascular disease

        Clinical evidence of bleeding diathesis or coagulopathy.

        Patients with known hypersensitivity of Chinese hamster ovary cell products or other
        recombinant human antibodies.