Clinical Trial Finder

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.

Arms

Experimental: Arm A (MRI-guided laser ablation)

MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression

Experimental: Arm B (MRI-guided laser ablation, doxorubicin, etoposide)

MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles) Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first

Interventions

Device: - MRI-guided laser ablation

Drug: - Doxorubicin

Drug: - Etoposide

Device: - Dynamic contrast-enhanced (DCE) MRI

Device: - Dynamic susceptibility contrast (DSC) MRI