Evaluation of FDOPA-PET/MRI in Pediatric Patients With CNS Tumors

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.