External Beam Radiation Therapy and Cetuximab Followed by Irinotecan and Cetuximab for Children and Young Adults With Newly Diagnosed Diffuse Pontine Tumors and High-Grade Astrocytomas

Inclusion Criteria:

- Patients must have either (1) histologic proof of a high-grade astrocytoma reviewed by
a POETIC institutional pathologist or (2) a radiological diagnosis via MRI scan of a
typical diffuse pontine tumor made by a POETIC institutional neuroradiologist.
Patients with a radiological diagnosis via MRI scan of a typical diffuse pontine tumor
will be enrolled on the diffuse pontine tumor arm of the study regardless of histology
in cases that are biopsied. Note: For collaborating non-POETIC institutions, the
reviews may be done by an institutional pathologist/neuroradiologist.

- Patients must begin study prescribed therapy within 42 days of neurosurgical resection
or biopsy of the tumor (high-grade astrocytoma patients) or radiological diagnosis
(diffuse pontine tumor patients).

- Age ≥ 3-years and < 22-years-old.

- Brain MRI (and any other studies done according to clinical indications) must not show
any definitive evidence of leptomeningeal or extra-neural metastases.

- ANC ≥ 1000/μL and platelet count ≥ 100,000/μL

- Patients must have adequate organ function as defined by:

- Hepatic: total bilirubin < 1.5 mg/dl, AST ≤ 2.5 x the upper limit of normal.

- Renal: serum creatinine ≤ 1.5 x the upper limit of normal for age, or calculated
creatinine clearance or nuclear GFR ≥ 70 ml/min/1.73 m2.

- The patient, or for minors, a parent or legal guardian, must give informed written
consent indicating they are aware of the investigational nature of this study.

Exclusion Criteria:

- Evidence of leptomeningeal or extra-neural metastatic disease.

- Prior radiation therapy or chemotherapy

- Pregnancy, mothers unwilling to refrain from breast-feeding, and sexually mature
patients unwilling to practice an effective form of birth control.

- Other significant concomitant medical illnesses that would compromise the patient's
ability to receive all prescribed study therapy.

- Prior therapy which specifically and directly targets the EGFR pathway.

- Prior severe infusion reaction to a monoclonal antibody.

- Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension,
unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled
congestive heart failure, and cardiomyopathy with decreased ejection fraction.

- Patients with known Gilbert's Syndrome.