Clinical Trial Finder

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

• - 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

Arms

Experimental: Dasatinib+Everolimus

Dasatinib = 60 mg/m2 orally twice daily Everolimus = starting dose of 3.0 mg/m2, with titration of dosing after first cycle to keep everolimus trough level of 5-15 ug/ml Both agents will be taken daily for 28 day cycles. Cycles will be repeated every 28 days and patients may receive up to 24 cycles.

Interventions

Drug: - Dasatinib

60 mg/m2 orally twice daily

Drug: - Everolimus

3.0 mg/m2, with titration of dosing after first cycle to keep trough level of 5-15 ug/ml