Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma
Condition: Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma
MeSH terms: Glioma; Astrocytoma; Ependymoma; Medulloblastoma; Oligodendroglioma; Spinal Cord Neoplasms; Recurrence
Intervention: Bevacizumab; Fludeoxyglucose F-18; Irinotecan Hydrochloride
Intervention description: Given IV; Undergo fludeoxyglucose F18 PET; Given IV
Intervention MeSH terms: Deoxyglucose; Bevacizumab; Antineoplastic Agents, Immunological; Irinotecan; Camptothecin; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G; Fluorodeoxyglucose F18
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 97.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving bevacizumab together with irinotecan works in
      treating young patients with recurrent, progressive, or refractory glioma, medulloblastoma,
      ependymoma, or low grade glioma. 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 glioma by blocking blood flow to the tumor. Drugs used in
      chemotherapy, such as irinotecan, 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 irinotecan may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed high-grade glioma (WHO grade III or IV) at any site within
             the brain, including the following:

               -  Anaplastic astrocytoma

               -  Glioblastoma multiforme (including giant cell and gliosarcoma subtypes)

               -  Anaplastic oligodendroglioma

               -  Anaplastic ganglioglioma

               -  Anaplastic oligoastrocytoma

               -  Diffuse brain stem glioma

                    -  Histologic confirmation not required

               -  Histologically confirmed medulloblastoma

               -  Histologically confirmed ependymoma

               -  Primary spinal cord malignant glioma with measurable metastatic disease within
                  the brain

                    -  Histologic confirmation required

                    -  Neuraxis dissemination allowed provided there is bidimensionally measurable
                       disease within the brain and spinal cord

               -  Low grade glioma at any site within the brain with or without spinal cord disease

          -  Recurrent, progressive, or refractory disease (must have received prior
             chemoradiotherapy)

          -  No more than 2 prior chemotherapy regimens following relapse

          -  Bidimensionally measurable disease, defined as ≥ 1 lesion that can be accurately
             measured in ≥ 2 planes

          -  If there is spinal cord disease as well, response assessment will be based only upon
             the measurable tumor in the brain

          -  No diffuse gliomatosis cerebri with < 1 discrete, measurable lesion

          -  No evidence of new symptomatic CNS hemorrhage (> grade 2) within the past 2 weeks

          -  No central non-cerebellar PNET's (e.g., cerebral PNET or pineoblastoma)

          -  No spinal cord tumors only

          -  Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤
             16 years of age)

          -  Absolute neutrophil count ≥ 1,500/mm³ (unsupported)

          -  Platelet count ≥ 100,000/mm³ (unsupported)

          -  Hemoglobin > 8 g/dL (support allowed)

          -  Creatinine normal

          -  BUN < 25 mg/dL

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  ALT and AST ≤ 3 times ULN

          -  Neurological deficits must be stable for ≥ 1 week prior to study entry

          -  No active renal, cardiac (congestive cardiac failure, myocarditis), or pulmonary
             disease

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for ≥ 6 months after
             completion of study treatment

          -  No clinically significant unrelated systemic illness that would preclude study
             treatment, including any of the following:

               -  Serious infections

               -  Significant cardiac, pulmonary, hepatic, or other organ dysfunction

               -  No uncontrolled systemic hypertension, defined as systolic blood pressure (BP)
                  and/or diastolic BP > 95th percentile for age

               -  No stroke, myocardial infarction, or unstable angina within the past 6 months

               -  No clinically significant peripheral vascular disease

               -  No significant traumatic injury within the past 6 weeks

               -  No evidence of bleeding diathesis, coagulopathy, or PT INR > 1.5

               -  Urine protein/creatinine ratio ≤ 1.0

               -  No abdominal fistula or gastrointestinal perforation within the past 6 months

               -  No serious nonhealing wound, ulcer, or bone fracture

          -  At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for
             nitrosoureas)

          -  At least 7 days since prior investigational or biologic agents (3 weeks if patient
             experienced ≥ grade 2 myelosuppression or if agent has a prolonged half-life)

          -  More than 7 days since prior minor surgery

          -  More than 12 weeks since prior craniospinal or focal irradiation to primary tumor or
             other sites

          -  At least 4 weeks since prior major surgery and recovered

          -  At least 3 months since prior autologous bone marrow or stem cell transplantation

          -  At least 2 weeks since prior colony-forming growth factors (i.e., filgrastim [G-CSF],
             sargramostim [GM-CSF], epoetin alfa)

          -  No prior bevacizumab or irinotecan hydrochloride

          -  No anticipated surgery during treatment

          -  No concurrent prophylactic G-CSF, GM-CSF, or epoetin alfa

          -  Concurrent dexamethasone allowed provided the dose is stable or decreasing over the
             past week

          -  No other concurrent anticancer or investigational drugs

          -  No concurrent medications that may interfere with study (e.g., immunosuppressive
             agents other than corticosteroids)

          -  No concurrent therapeutic anticoagulation

          -  No concurrent nonsteroidal anti-inflammatory drugs, clopidogrel bisulfate,
             dipyridamole, or acetylsalicylic acid (aspirin) > 81 mg/day