Study of GDC-0084 in Pediatric Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma or Diffuse Midline Gliomas

Inclusion Criteria:

* Age greater than or equal to 2 years and less than 22 years at the time of enrollment
* Subjects 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 subjects are eligible without histologic confirmation.
  * Biopsied typical DIPG: WHO grade II diffuse astrocytoma (IDH WT or IDH 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. Subjects with a typical DIPG who undergo a biopsy may be eligible for the study if the tumor does not harbor the H3 K27M mutation, yet eligibility is restricted to diffuse astrocytoma, anaplastic astrocytoma or glioblastoma, IDH WT or IDH NOS, tumors.
  * 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.
* Subjects must have localized, non-metastatic disease; MRI of spine must be performed if disseminated disease is suspected by the treating physician.
* Subjects 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 subjects aged 16 years or younger and Karnofsky for subjects older than 16 years). Subjects 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.
* Subjects 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.
* Subjects must have adequate organ function documented at the time of study enrollment as follows:

  * Bone marrow: Hemoglobin ≥ 8g/dL \[may have received packed red blood cell transfusion\], absolute neutrophil count (ANC) ≥ 1000/mm\^3, platelets ≥ 50,000/mm\^3 \[transfusion independent\].
  * Renal: Normal serum creatinine based on age (Age 2 to ≤5: 0.8; Age \>5 to \<10: 1.0; Age \>10 to \<15: 1.2; Age ≥15: 1.5) or GFR ≥ 70 mL/min/1.73m\^2
  * Hepatic: ALT and AST \< 3 × the institutional upper limit of normal (ULN), total bilirubin concentration \< 1.5 x the institutional ULN, albumin ≥ 2g/dL.
* Shortening fraction of ≥ 27% by ECHO or ejection fraction of ≥ 50% by gated radionuclide study.
* Subjects must not have congenital long QT syndrome and QTc \< 500 ms.
* Subjects must not require the use of any CYP34A-inducing or -inhibiting agents, with the exception of corticosteroids.
* Female subjects of childbearing potential must not be pregnant or breastfeeding a child. Female subjects of childbearing potential aged 10 years or older must have a negative serum or urine pregnancy test.
* Subjects 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.
* Informed consent: All subjects 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:

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