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

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).


Eligibility Criteria:
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