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 candidatesfor 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 thetreating neurosurgeon.

• Unequivocal evidence of tumor progression by MRI

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

• Recurrent lesions with dimension and contour that are determined by the treatingneurosurgeon 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 leftventricular ejection fraction ≥ 50% by echocardiogram within the past 1 year priorto 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 ofMLA):

• 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 ofprior therapy to no more than grade 1 toxicity.

• At the time of registration, patient must be at least 4 weeks from other priorcytotoxic 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 andfor the duration of study participation. Should a woman become pregnant or suspectshe is pregnant while participating in this study, she must inform her treatingphysician immediately.

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

Exclusion Criteria:

ARM A

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

• Multi-focal or metastatic disease.

• Pregnant and/or breastfeeding. Premenopausal women must have a negative serum orurine 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 doseof > 200 mg/m2 doxorubicin.

• More than 2 prior relapses (not counting the current relapse being treated on thisstudy).

• Currently receiving any other investigational agents that are intended as treatmentsof the relapsed tumor.

• Multi-focal or metastatic disease.

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

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, recent heart attack within the previous 12 months or severe heartproblems, or psychiatric illness/social situations that would limit compliance withstudy requirements.

• Pregnant and/or breastfeeding. Premenopausal women must have a negative serum orurine 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.