Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors

Inclusion Criteria:

ARM A

- Presumed pediatric gliomas (grades I-IV) on MRI that are determined to be candidates
for MLA by the treating neurosurgeon

- Age 3 to ≤ 21

- Karnofsky/Lansky performance status ≥ 60%

ARM B

- Recurrent pediatric brain tumors determined candidates for MLA as determined by the
treating neurosurgeon.

- Unequivocal evidence of tumor progression by MRI

- There must be an interval of at least 12 weeks from the completion of radiotherapy to
study registration except if there is unequivocal evidence for tumor recurrence per
RANO criteria. When the interval is less than 12 weeks from the completion of
radiotherapy, the use of PET scan is allowed to differentiate between evidence of
tumor recurrence and pseudoprogression.

- Recurrent lesions with dimension and contour that are determined by the treating
neurosurgeon to be appropriate for MLA.

- Age 3 to ≤ 21

- Karnofsky/Lansky performance status ≥ 60%

- Adequate cardiac function as determined by a shortening fraction ≥ 27% or left
ventricular ejection fraction ≥ 50% by echocardiogram within the past 1 year prior to
registration.

- Prior anthracycline therapy does not exceed 200 mg/m^2 total cumulative dose.

- Adequate bone marrow and hepatic function as defined below (must be within 7 days of
MLA):

- Absolute neutrophil count (ANC) ≥ 1000/mcl (G-CSF is allowed)

- Platelets ≥ 100 K/cumm

- Hemoglobin ≥ 9 g/dL (pRBC transfusion +/- ESA are allowed)

- ALT ≤ 3 x ULN

- AST ≤ 3 x ULN

- ALP ≤ 3 x ULN. If ALP is > 3 x ULN, GGT must be checked and be ≤ 3 x ULN.

- Bilirubin ≤ 2 x ULN

- At the time of registration, patient must have recovered from the toxic effects of
prior therapy to no more than grade 1 toxicity.

- At the time of registration, patient must be at least 4 weeks from other prior
cytotoxic chemotherapy.

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and for
the duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she must inform her treating physician
immediately.

- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

ARM A

- Currently receiving or scheduled to receive any other therapies intended to treat the
newly diagnosed glioma prior to MLA and the first post-MLA blood collection for
correlative studies.

- Multi-focal or metastatic disease.

- Pregnant and/or breastfeeding. Premenopausal women must have a negative serum or urine
pregnancy test within 14 days of study entry.

- Inability to undergo MRI due to personal or medical reasons.

- Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.

ARM B

- Prior treatment with bevacizumab within 12 weeks of study entry.

- Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or
other anthracyclines and anthracenediones that is equivalent to a total dose of > 200
mg/m2 doxorubicin.

- More than 2 prior relapses (not counting the current relapse being treated on this
study).

- Currently receiving any other investigational agents that are intended as treatments
of the relapsed tumor.

- Multi-focal or metastatic disease.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to doxorubicin or other agents used in the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, recent heart attack within the previous 12 months or severe heart
problems, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant and/or breastfeeding. Premenopausal women must have a negative serum or urine
pregnancy test within 14 days of study entry.

- Inability to undergo MRI due to personal or medical reasons.

- Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.