Study of Dasatinib in Combination With Everolimus for Children and Young Adults With Gliomas Harboring PDGFR/FGFR Alterations

Inclusion Criteria:

- Histological confirmation of a newly diagnosed high-grade glioma or DIPG (Stratum A)

- Histological confirmation (at diagnosis or relapse) of a recurrent or progressive
grade II-IV glioma (including DIPG) (Stratum B)

- Participants must have a genomic (DNA and/or RNA) alteration (mutation, fusion, and/or
amplification) involving PDGF-A, PDGF-B, PDGFR-A, PDGFR-B, FGF1, FGF3, FGFR1 or FGFR3,
as identified by tumor sequencing.

- Age at enrollment: Greater than 1 year and less than 30 years

- BSA (body surface area): BSA greater than 0.3 m2

- Karnofsky (Measure of performance for cancer patients where 100% represents perfect
health) > 50% for patients > 16 years of age and Lansky (Measure of performance for
pediatric cancer patients where 100% represents perfect health) > 50% for patients <
16 years of age. Neurologic deficits in patients with CNS tumors must have been
relatively stable for a minimum of 7 days. Patients who are unable to walk because of
paralysis, but who are able to sit in a wheelchair, will be considered ambulatory for
the purpose of assessing the performance score.

- Adequate bone marrow function

- Adequate liver function

- Adequate renal and metabolic function

- Patients with known seizure disorder must have seizures adequately controlled with
non- enzyme inducing antiepileptic medications

- No increase in steroid dose within the past 7 days

- Primary brain or spine tumor are eligible, including tumors with metastases, multiple
lesions.

- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy.

- Myelosuppressive chemotherapy: Must not have received within 3 weeks.

- Hematopoietic growth factors: At least 7 days since the completion of therapy with a
growth factor, 14 days for long- acting.

- Biologic (anti-neoplastic agent): At least 7 days or 3 half-lives (whichever is
longer) since the completion of therapy.

- ≥ 12 weeks must have elapsed from craniospinal radiation; ≥ 2 weeks must have elapsed
from focal radiation.

- > 3 weeks from major surgery. If recent craniotomy, adequate wound healing must be
determined by neurosurgical team.

- Autologous Stem Cell Transplant or Rescue: No evidence of active graft vs. host
disease and ≥ 4 weeks must have elapsed.

- All patients and/or a legal guardian must sign institutionally approved written
informed consent and assent documents.

Exclusion Criteria:

- Patients who are breastfeeding, pregnant or refuse to use an effective form of birth
control are excluded.

- Patients with uncontrolled infection are excluded.

- Patients with known bleeding disorders or more than punctate intratumoral hemorrhage
are excluded.

- Patients receiving other anti-neoplastic agents are excluded.

- Patients on enzyme-inducing anticonvulsive agents are excluded

- Patients requiring strong CYP3A4 or PGP inducers or inhibitors are excluded
(verapamil, diltiazem, aprepitant, voriconazole, posaconazole, fluconazole (higher
dose), phenytoin, carbamazepine, phenobarbital, (levetiracetam is ok), rifampin,
rifabutin).

- Patients requiring anticoagulation or with uncontrolled bleeding are excluded.

- Patients on steroids for symptom management must be on a stable dose for 7 days prior
to start of treatment.

- Patients within 1 year of allogeneic stem cell transplant, patients with active GVHD
or requiring immunosuppression are excluded.

- Previous hypersensitivity to rapamycin or rapamycin derivatives