GDC-0084 after Radiation Therapy in Treating Pediatric Patients with Newly Diagnosed Diffuse Intrinsic Pontine Glioma or Diffuse Midline Glioma

Inclusion Criteria

• Patients must have one of the following newly diagnosed tumors: * Non-biopsied typical DIPG, defined as a tumor with a pontine epicenter and diffuse intrinsic involvement of the pons. These patients are eligible without histologic confirmation. * Biopsied typical DIPG: World Health Organization (WHO) grade II diffuse astrocytoma (IDH wild type [WT] or IDH not otherwise specified [NOS]), WHO grade III anaplastic astrocytoma (IDH WT or IDH NOS), WHO grade IV glioblastoma (IDH WT or IDH NOS), or diffuse midline glioma, H3 K27M mutant. ** Note: Patients with typical DIPG who undergo a biopsy may be eligible for the study if the tumor does not harbor the H3 K27M mutation, provided the tumor is diffuse astrocytoma, anaplastic astrocytoma or glioblastoma IDH WT or IDH NOS). * Atypical brainstem glioma: diffuse midline glioma, H3 K27M mutant. * Non-brainstem midline glioma, defined as tumors with an epicenter within midline structures, including the thalamus, spinal cord, and cerebellum: diffuse midline glioma, H3 K27M mutant.
• Patients must have localized, non-metastatic disease; MRI of spine must be performed if disseminated disease is suspected by the treating physician
• Patients must be able to start radiation therapy no later than 42 days after radiographic diagnosis or surgery, whichever date is later
• Performance score >= 50 (Lansky for research participants aged 16 years or younger and Karnofsky for participants older than 16 years). 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
• Patients must not have received any prior therapy, including prior treatment with a PI3 kinase, mTOR, or PI3K/mTOR inhibitor, other than surgery and/or steroids
• Hemoglobin > = 8g/dL (may have received packed red blood cell transfusion) (at the time of study enrollment)
• Absolute neutrophil count (ANC) >= 1000/mm^3 (at the time of study enrollment)
• Platelets >= 50,000/mm^3 (transfusion independent) (at the time of study enrollment)
• Normal serum creatinine based on age as shown below or glomerular filtration rate (GFR) >= 70 mL/min1.73m^2 (at the time of study enrollment): * Age (years): 2 to =< 5: Maximum serum concentration (mg/dL) 0.8 * Age (years): 5 < age < 10: Maximum serum concentration (mg/dL) 1.0 * Age (years): 10 < age < 15: Maximum serum concentration (mg/dL) 1.2 * Age (years): >= 15: Maximum serum concentration (mg/dL) 1.5
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x the institutional upper limit of normal (ULN) (at the time of study enrollment)
• Total bilirubin concentration < 1.5 x the institutional ULN (at the time of study enrollment)
• Albumin >= 2g/dL (at the time of study enrollment)
• Shortening fraction of >= 27% by echocardiogram (ECHO) or ejection fraction of >= 50% by gated radionuclide study
• Patients must not have congenital long QT syndrome and corrected QT (QTc) < 500 ms
• Patients must not require the use of any CYP34A-inducing or -inhibiting agents, with the exception of corticosteroids
• Female patients of childbearing potential must not be pregnant or breastfeeding a child. Female patients of childbearing potential aged 10 years or older must have a negative serum or urine pregnancy test
• Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which can be abstinence, while being treated on this study and for 3 additional months after completion of therapy
• All patients and/or their parents or legally authorized representatives must sign a written consent. Assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria

• Patients with evidence of tumor infiltration of three or more cerebral lobes on diagnostic MRI
• Patients with any clinically significant, unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient’s ability to tolerate protocol therapy or would probably interfere with the study procedures or results
• Diabetic patients who require insulin therapy
• Patient with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities as documented by a standard 12-lead electrocardiogram (ECG)
• Patients receiving any other anticancer (glucocorticoids are acceptable) or investigational drug therapy
• Patients unable to return for follow-up visits or obtain follow-up studies required to assess toxicity of therapy
• Patients with disseminated disease
• Pregnant patients or patients breast-feeding a child