study of dasatinib in combination with everolimus for children and young adults with gliomas harboring platelet-derived growth factor receptor (pdgfr) alterations

Conditions: Glioma; High Grade Glioma; Pontine Tumors

Summary: 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