Phase I Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)

Inclusion Criteria:

ALL RESEARCH PARTICIPANTS

- Diagnosis of high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). If
histologic confirmation was obtained, diagnosis must be one of the following:
anaplastic astrocytoma (WHO grade 3), anaplastic oligodendroglioma (WHO grade 3),
anaplastic oligoastrocytoma (WHO grade 3), anaplastic ganglioglioma (WHO grade 3),
pleomorphic xanthoastrocytoma with anaplastic features (WHO grade 3), malignant
glioneuronal tumor, glioblastoma, or gliosarcoma (WHO grade 4)

- Age > or = 2 years and < or = 21 years

- Performance score > or = 50 (Lansky for research participants < or = 16 years and
Karnofsky for those > 16 years).

- Neurological deficits must be stable on a fixed or decreasing dose of dexamethasone
for > or = 7 days before study enrollment

- Adequate organ function at the time of enrollment as follows:

- Bone marrow: Hemoglobin > or = 8g/dL [may have received packed red blood cell
transfusion], absolute neutrophil count (ANC) > or = 1000/mm^3, platelets > or =
100,000/mm^3 [transfusion independent])

- Renal: Normal serum creatinine based on age as shown below or GFR >
70ml/min/1.73m^2:

- Age < or = 5 years: 0.8 mg/dL maximum

- Age 5 to 10 years: 1.0 mg/dL maximum

- Age 10 to 15 years: 1.2 mg/dL maximum

- Age > 15 years: 1.5 mg/dL maximum

- Hepatic: SGPT and SGOT < 3x the institutional upper limit of normal (ULN), total
bilirubin concentration < 1.5x the institutional ULN, albumin > or = 2g/dL

- Recovery to < or = grade 1 from all significant toxicities of previous therapies

- Female research participants > or = 10 years of age or post-menarchal must not be
pregnant (confirmed by serum or urine pregnancy test within 1 week of study
enrollment) or breastfeeding

- Female research participants of childbearing age or males research participants of
child fathering potential must agree to use safe contraceptive methods for the
duration of the study and for 3 months thereafter

Inclusion Criteria:

STRATUM A

- Diagnosis of recurrent or progressive HGG or DIPG.

- Irradiation: Interval from the last dose of local radiation therapy (RT),
craniospinal RT, and palliative RT for symptomatic disease > or = 3 months, > or = 6
months, and > or = 2 weeks before study enrollment, respectively

- Myelosuppressive chemotherapy: Interval > or = 6 weeks and > or = 4 weeks from last
dose of nitrosourea and other chemotherapy drugs before study enrollment,
respectively. However, interval must be > or = 1 week from last dose of oral
etoposide and other drugs administered at low doses (metronomic regimen) before study
enrollment

- Small-Molecule Inhibitors: Interval > or = 1 week from last dose before study
enrollment. If a previously used agent has a prolonged half-life, the appropriate
interval will be determined after consultation with the principal investigator

- Monoclonal Antibodies: Interval > or = 3 half-lives before study enrollment. Such
cases will need to be discussed with the principal investigator

- High-Dose Chemotherapy with Stem-Cell Rescue: Interval > or = 3 months before study
enrollment

- Cancer Vaccines and Convection-Enhanced Therapies: Interval > or = 1 month before
study enrollment

- Growth Factors: Interval > or = 1 week and > or = 2 weeks before study enrollment for
standard and long-acting growth factors (e.g., pegfilgrastim), respectively

Inclusion Criteria:

STRATUM B

- Completion of local RT with or without concomitant chemotherapy including
temozolomide and radiosensitizing agents (e.g., carboplatin, vorinostat) outside the
context of a clinical trial. Any agent administered during RT should have a short
half-life so that it should already be completely eliminated by the start of this
therapy. If other agents were used concurrently with RT, they will need to be
discussed with the principal investigator to assess eligibility

- Interval > or = 4 weeks and < or = 8 weeks from the completion of radiochemotherapy

Exclusion Criteria: ALL RESEARCH PARTICIPANTS

- Metastatic disease

- Concomitant use of other anticancer (except for corticosteroids) or experimental
agents

- Use of enzyme-inducing anticonvulsants (EIACs). A minimum interval of 10 days
between the last dose of EIAC and start of this therapy will be required for research
participants who were previously receiving such medications.

- Pregnant or lactating patients

- Research participants with other clinically significant medical disorders that could
compromise their ability to tolerate protocol therapy or would interfere with the
study procedures or results

- Prior therapy with a PDGFR or c-Met inhibitor

- Body surface area > or = 1.8m2on dosage levels 2b, 3, and 4