Study of Dasatinib in Combination With Everolimus for Children and Young Adults With Gliomas Harboring Platelet-Derived Growth Factor Receptor (PDGFR) Alterations

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.