Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan for Patients With High Grade Glioma

For children with High-grade gliomas (HGG) including HGG presenting within the midline
structures of the brain and spine, outcome remains poor and the majority of children die from
this disease. The current study will use a new treatment approach based on each patient's
tumor gene expression, whole-exome sequencing (WES), whole-genome sequencing (WGS), targeted
panel profile (UCSF 500 gene panel), quantitative proteomics, and RNA-Seq. This treatment
strategy has shown promising results in adult patients with solid tumors and is currently
being explored in children with DIPG, neuroblastoma and other solid tumors. The current study
will test the efficacy of such an approach in children with HGG for which outcomes remain
dismal.

Inclusion Criteria:

- Patients with newly diagnosed HGG (including midline HGG but excluding DIPG), who
undergo tissue collection as part of standard of care. Patients with disseminated
disease are not eligible, and MRI of the spine must be performed if disseminated
disease is suspected by the treating physician. Primary spinal cord tumors are
eligible.

- Enrollment within 3 weeks of the start of radiation therapy.

- Start of radiation therapy within 6 weeks from initial tissue diagnosis.

- Age ≤ 21 years

- Karnofsky score ≥ 50 for patients ≥ 16 years of age and Lansky score ≥ 50 for patients
≤15 years of age. 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

- Adequate tissue for molecular profiling (>25% tumor content).

- The effects of the current treatment paradigm on the developing human fetus are
unknown. For this reason, females of child-bearing potential and males 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, and 30 days after
completion of study drug administration. Should a female become pregnant or suspect
she is pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately. Males treated or enrolled on this protocol
must also agree to use adequate contraception prior to the study, for the duration of
study participation, and 30 days after completion of study drug administration.

- Adequate neurologic function defined as: Patients with seizure disorder may be
enrolled if seizures are well controlled.

- Ability by patient or parent/legal guardian to understand a written informed consent
document, and the willingness to sign it.

Exclusion Criteria:

- Patients who are currently enrolled on another therapeutic clinical trial. Individual
cases should be discussed with the study chair.

- Patients who are currently taking any anti-cancer directed therapy. Steroids are not
considered anti-cancer therapy. The use of temozolomide during radiation therapy is
allowed at standard dosing (maximum 75 to 90 mg/m^2 daily for a total of 42 days). Any
other schedule(s) need to be discussed with the study chair.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Female patients of childbearing potential must not be pregnant or breast-feeding.
Female patients of childbearing potential must have a negative serum or urine
pregnancy test prior to the start of therapy (as clinically indicated).

- Patients with inability to return for follow-up visits or obtain follow-up studies
required to assess toxicity to therapy.