Evaluation of FDOPA-PET/MRI in Pediatric Patients With CNS Tumors
Evaluation of FDOPA-PET/MRI in Pediatric Patients With CNS Tumors
To determine if FDOPA-PET/MRI imaging can predict response to treatment of bevacizumab.
Evaluate the feasibility of using FDOPA-PET/MRI pediatric patients with CNS tumors. Positive
 results in this small study would provide the data needed to expand the study to validate the
 use in a larger population of pediatric patients. Validating the use of FDOPA-PET imaging as
 an early predictor for response to anti-angiogenic therapy could greatly impact the standard
 of care for treating and evaluating pediatric brain tumors and provide a useful biomarker for
 assessing experimental therapeutics.
Inclusion Criteria:

 -  Patient must have histological verification of one of the eligible diagnosis listed
 below. Biopsy is required at time of diagnosis, with the exception of optic pathway
 tumors. Patients with spinal cord disease are eligible if they have a lesion >1 cm in
 2 dimensions. The following histologies are eligible:

 -  Astrocytoma variants: fibrillary, protoplasmic, mixed

 -  Pilocytic astrocytoma, including pilomyxoid variants

 -  Pleomorphic xanthoastrocytoma

 -  Infantile desmoplastic astrocytoma

 -  Ganglioneuroma

 -  Oligodendroglial tumor

 -  Mixed glioma (including oligoastrocytoma)

 -  Anaplastic astrocytoma

 -  Anaplastic oligoastrocytoma

 -  Anaplastic oligodendroglioma

 -  Anaplastic ganglioglioma

 -  Glioblastoma multiforme (including giant cell and gliosarcoma types)

 -  Medulloblastoma

 -  Ependymoma

 -  Other rare malignant CNS tumors (i.e., pineal blastoma, small cell astrocytoma,
 etc.)

 -  Patient must be ≤ 21 years of age at time of study enrollment.

 -  Patient must have measurable residual disease, defined as tumor that is measurable in
 two perpendicular diameters on MRI. Diffuse leptomeningeal disease is not considered
 measurable.

 -  Patient must have a Lansky or Karnofsky performance of >40% corresponding to ECOG
 categories 0, 1, or 2. Karnofsky will be used for patients >16 years of age and Lansky
 for patients <16 years of age. Patients who are unable to walk because of paralysis,
 but who are up in a wheelchair, will be considered ambulatory for the purpose of
 assessing the performance score.

 -  Patient must have a life expectancy of >8 weeks.

 -  Patient must have fully recovered from the acute toxic effects of all prior
 chemotherapy or radiation prior to entering this study.

 -  Patient must have recovered from any surgical procedure before enrolling on this
 study.

 -  Hypertensive patients are eligible provided the hypertension is well controlled (95th
 percentile for age and height if patient ≤17 years) on stable doses of medication.
 (See Appendices I and II for tables of blood pressure based on age and gender).

 -  Patients receiving corticosteroids are eligible provided the dose is stable or
 decreasing for at least 7 days.

 -  Patient must have adequate bone marrow function (including status post-SCT) defined
 as:

 1. Peripheral absolute neutrophil count (ANC) ≥1000/uL (must not have received G-CSF
 within the prior 7 days)

 2. Platelet count ≥ 100,000/uL (transfusion independent)

 3. Hemoglobin ≥ 8.0 gm/dL (may receive pRBC transfusions)

 -  Patient must have adequate renal function defined as:

 1. Creatinine clearance or radioisotope GFR ≥70ml/min/1.73 m2 or

 2. A serum creatinine based on age/gender as follows:

 -  1 month to < 6 months, male max 0.4, female max 0.4

 -  6 months to < 1 year, male max 0.5, female max 0.5

 -  1 to <2 years, male max 0.6, female max 0.6

 -  2 to < 6 years, male max 0.8, female max 0.8

 -  6 to <10 years, male max 1.0, female max 1.0

 -  10 to <13 years, male max 1.2, female max 1.2

 -  13 to <16 years, male max 1.5, female max 1.4

 -  16 years, male max 1.7, female max 1.4

 -  Urine protein should be screened by dipstick analysis. If protein ≥ 2+ on dipstick,
 then Urine Protein Creatinine (UPC) ratio should be calculated. If UPC ratio >1,
 24-hour urine protein should be obtained and the level should be <1000 mg/24 hours for
 patient enrollment.

 Note: UPC ratio of spot urine is an estimation of the 24 hour urine protein excretion- a
 UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is
 calculated using of the following formulae:

 [urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/dL
 [(urine protein x 0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L

 -  Patient must have adequate liver function defined as:

 1. Total bilirubin ≤1.5x upper limit of normal for age (ULN)

 2. SGPT (ALT) ≤ 2.5 x the upper limit of normal (ULN) for age

 -  Patients with a seizure disorder are eligible if well-controlled on anticonvulsants.
 If on a non-enzyme inducing anticonvulsant, the irinotecan dose will be adjusted as
 outline in treatment plan.

 -  Sexually active patients of childbearing potential must agree to use an effective
 method of contraception during the study and for at least 6 months after the
 completion of bevacizumab therapy.

 -  Patient or legally authorized representative must be able to understand and willing to
 sign a written informed consent document.

 Exclusion Criteria:

 -  Patient must not have had myelosuppressive chemotherapy ≤ 3 weeks prior to entry onto
 this study (or 6 weeks if prior nitrosourea).

 -  Patient must not have had any anti-neoplastic biologic agent ≤7 days prior to entry
 onto this study (or at least 3 half-lives for biologic agents with a long half-life).

 -  Patient must not have received craniospinal radiotherapy or involved field
 radiotherapy to the local tumor (and/or tumor designated as "measurable" for protocol
 purposes) ≤ 24 weeks prior to study entry; focal radiation to areas of symptomatic
 metastatic disease must not be given within 14 days of study entry.

 -  Patient must not have received bevacizumab, or other anti-VEGF inhibitor in the last 3
 months.

 -  Patient must not require a major surgical procedure ≤ 21 days prior to beginning
 therapy.

 -  Patient must not require an intermediate surgical procedure ≤14 days prior to
 beginning therapy.

 -  Patient must not require a minor surgical procedure (i.e., Broviac line or infusaport
 placement) ≤ 7 days prior to beginning therapy, and the wound must be healed prior to
 initiation of therapy.

 -  There should be no anticipation of need for major surgical procedures during the
 course of the study.

 -  Patient must not have received any growth factors ≤7 days of entry onto this study.

 -  Patient must not be taking NSAIDS, clopidogrel, dipyridamole, or aspirin therapy >81
 mg/day.

 -  Patient must not have a serious or non-healing wound, ulcer, or bone fracture.

 -  Patient must not require sedation for imaging purposes.

 -  Patient must not be receiving an investigational drug.

 -  Patient must not be receiving any other anti-cancer agent.

 -  Patient must not have an uncontrolled infection.

 -  Patient must not have a history of abdominal fistula, gastrointestinal perforation or
 intra-abdominal abscess ≤ 6 months prior to study entry.

 -  Patient must not have a known bleeding diathesis or coagulopathy.

 -  Patient must not have had significant vascular disease (e.g., Moya-Moya, aortic
 aneurysm requiring surgical repair, deep venous or arterial thrombosis) ≤ 6 months
 prior to study entry.

 -  Patient must not have a known thrombophilic condition (i.e. protein S, protein C or
 antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation,
 homocysteinemia, or antiphospholipid antibody syndrome). Testing is not required in
 patients without a thrombophilic history.

 -  Patient must not have evidence of a new CNS hemorrhage greater than 0.5cm on baseline
 MRI obtained ≤ 14 days prior to study enrollment.

 -  Patient must not have a history of stroke, myocardial infarction, transient ischemic
 attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or
 greater congestive heart failure ≤ 6 months prior to study entry.

 -  Patient must not have serious and inadequately controlled cardiac arrhythmia

 -  Patient must not be pregnant or breastfeeding.

 -  Patient must not have a known hypersensitivity to Chinese hamster ovary cell products
 or other recombinant human antibodies.

 -  Patient must not be known to be HIV-positive on combination antiretroviral therapy
 because of the potential for pharmacokinetic interactions with study therapy. In
 addition, these patients are at increased risk of lethal infections when treated with
 marrow-suppressive therapy.

 -  Patient must not have any contraindications to MRI imaging including implanted medical
 devices and metal objects which may be adversely affected by MRI imaging. All subjects
 will be required to complete a standard MRI screening form prior to imaging.