Optune Delivered Electric Field Therapy in Treating Children with Recurrent, Progressive, or Refractory High-Grade Glioma or Supratentorial Ependymoma or Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Inclusion Criteria

• The following inclusion criteria are required for all Stratum 2 patients
• Patient must be ≥ 3 but ≤ 21 years of age at the time of enrollment
• Patients with newly diagnosed DIPG * Patients with a typical DIPG on magnetic resonance (MR) imaging, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation ** Note: Patients with typical DIPG who undergo a biopsy are eligible provided the tumor is a diffuse glioma World Health Organization (WHO) Grade II-IV with OR without H3 K27M mutation * Patients with pontine lesions that do not meet these MR imaging criteria will be eligible if there is histologic confirmation diffuse glioma WHO Grade II-IV with H3 K27M- mutation
• Subjects must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two planes * This disease must be located primarily in the pons
• Patients must not have received any prior anti-cancer therapy such as chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior steroids and/or surgery are allowed. If clinically indicated, enrolled patients may receive up to 5 fractions of radiotherapy prior to starting Optune therapy
• Radiation therapy and the Optune application start date must be at least 5 days after the date of a tumor biopsy if obtained. The Optune application start date must be at least 5 days after the date of a ventriculoperitoneal (VP) shunt or endoscopic third ventriculostomy (ETV) procedure. For patients starting Optune therapy within 10 days of VP shunt or ETV procedure, neurosurgical sign off to start therapy is required
• Absolute neutrophil count ≥ 1000/uL (within 7 days prior to enrollment unless otherwise indicated)
• Platelets ≥ 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment unless otherwise indicated)
• Hemoglobin ≥ 8g/dl (may receive transfusions) (within 7 days prior to enrollment unless otherwise indicated)
• Serum creatinine based on age/sex as noted or meet the criteria below (within 7 days prior to enrollment unless otherwise indicated) * Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) 0.8 (female) * Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) 1 (female) * Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) 1.2 (female) * Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) 1.4 (female) * Age: ≥ 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) 1.4 (female) OR - a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m^2 OR - a glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN) (within 7 days prior to enrollment unless otherwise indicated)
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 times institutional upper limit of normal (within 7 days prior to enrollment unless otherwise indicated)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 3 times institutional upper limit of normal (within 7 days prior to enrollment unless otherwise indicated)
• Albumin ≥ 2 g/dl (within 7 days prior to enrollment unless otherwise indicated)
• Patients must have a minimum head circumference of 44 cm
• During concurrent Optune therapy and RT, patients must be willing to use Optune ≥ 18 hours/day for at least 40 of the 49 days of the duration of the feasibility period. During subsequent cycles of Optune therapy alone, patients must be willing to use Optune ≥ 18 hours/day for at least 23 days in a 28-day cycle. During concurrent Optune therapy and RT and Optune therapy alone, patients must be willing to keep their head shaved throughout treatment

Exclusion Criteria

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results
• Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient’s first malignancy has been in remission for at least 5 years from the end of treatment
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with any distant intracranial or spinal metastasis on MRI or positive cerebrospinal fluid (CSF) are ineligible
• Patients for whom there is clinical suspicion of metastatic disease in the CSF or spine, must have MRI of spine and CSF obtained (lumbar puncture or through ommaya, external ventricular drain [EVD] or shunt) with negative cytology
• Patients with major skull defects (such as missing bone without replacement) are not eligible
• Patients with active implanted electronic devices in the brain or spinal cord such as programmable VP shunts, deep brain stimulators, vagus nerve stimulators, are not allowed
• Patients with pacemaker, defibrillator, or documented significant arrhythmia, are not allowed
• Patients with foreign body intracranially, such as bullet fragments, are not allowed, with the exception of VP-shunts (non-programmable) and Ommaya catheters
• Patients with history of hypersensitivity to conductive hydrogel are not eligible