Low accrual

This trial will evaluate the activity of dasatinib in combination with everolimus for children with gliomas harboring PDGFR alterations, including newly diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) after radiation (stratum A); and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).

Inclusion Criteria:

• Histological confirmation of a newly diagnosed high-grade glioma or diffuse intrinsic pontine glioma (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 or PDGFR-B, as identified by tumor sequencing.

• Age at enrollment: Greater than 1 year and less than 50 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 per protocol

• Adequate liver function per protocol

• Adequate renal and metabolic function per protocol

• 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.

• Radiation therapy:

  • Stratum A: ≥ 2 weeks and </= to 12 weeks must have elapsed from radiation.
  • Stratum B: ≥ 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 receiving other anti-neoplastic agents are excluded.
• Patients requiring strong CYP3A4 or PGP inhibitors are excluded (per protocol)
• 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