Dasatinib and Everolimus in Treating Children with Newly Diagnosed, Recurrent, or Progressive High-Grade Glioma with PDGFR Alterations

Inclusion Criteria

• Body surface area (BSA) greater than 0.3 m^2
• Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients < 16 years of age; neurologic deficits in patients with central nervous system (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
• Absolute neutrophil count (ANC) > 750
• Platelet count > 100,000/uL without platelet transfusion within the past 7 days
• Bilirubin < 1.5 x upper limit of normal
• Alanine aminotransferase (ALT) < 2.5 x upper limit of normal
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 m^2, or a serum creatinine based on age/gender as follows: * Age 1 to < 2 years maximum serum creatinine (mg/dL) 0.6 (male); 0.6 (female) * Age 2 to < 6 years maximum serum creatinine (mg/dL) 0.8 (male); 0.8 (female) * Age 6 to < 10 years maximum serum creatinine (mg/dL) 1 (male); 1 (female) * Age 10 to < 13 years maximum serum creatinine (mg/dL) 1.2 (male); 1.2 (female) * Age 13 to < 16 years maximum serum creatinine (mg/dL) 1.5 (male); 1.4 (female) * Age >=16 years maximum serum creatinine (mg/dL) 1.7 (male) 1.4 (female)
• Urine protein: creatinine (UPC) ratio of < 1; or a urinalysis that is negative for protein; or 24-hour urine protein level < 1000 mg/dL
• 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
• STRATUM A: Histological confirmation of a newly diagnosed high-grade glioma or DIPG
• STRATUM B: Histological confirmation (at diagnosis or relapse) of a recurrent or progressive grade II-IV glioma (including DIPG)
• Primary brain or spine tumor are eligible, including tumors with metastases, multiple lesions
• Prior therapies * 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 (6 weeks if prior nitrosourea) * Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor, 14 days for long- acting (e.g. PEG-filgrastim) * Biologic (anti-neoplastic agent): At least 7 days or 3 half-lives (whichever is longer) since the completion of therapy with a biologic agent * Radiation therapy: ** Strata A: >= 2 weeks and =< to 12 weeks must have elapsed from radiation ** Strata B: >= 2 weeks must have elapsed from focal radiation * Surgery: > 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 versus (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
• Participants must have a genomic (DNA and/or ribonucleic acid [RNA] alteration (mutation, fusion, and/or amplification) involving PDGF-A, PDGF-B, PDGFR-A, PDGFR-B, as identified by tumor (formalin-fixed, paraffin-embedded [FFPE] or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing; sequencing will be performed through the University of Michigan MI-ONCOSEQ study (Clinical Laboratory Improvement Act [CLIA]-certified), or other (non-university [U] of Michigan) CLIA-certified tumor DNA or RNA sequencing; for Michigan Oncology Sequencing Center (MI-ONCOSEQ), at least 1 mm cubed of tumor tissue or > 1 core biopsy of tumor tissue is required, fresh or formalin-fixed paraffin-embedded (FFPE)

Exclusion Criteria

• Patients who are breastfeeding, pregnant or refuse to use an effective form of birth control are excluded; abstinence is considered an effective form of birth control
• Patients with uncontrolled infection are excluded
• Other medications: * Patients receiving other anti-neoplastic agents are excluded * Patients requiring strong CYP3A4 or PGP inhibitors are excluded * 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 graft versus host disease (GVHD) or requiring immunosuppression are excluded
• Previous hypersensitivity to rapamycin or rapamycin derivatives