Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma

This is a phase 2 study involving a 1:1 randomization of 40 patients with recurrent or
refractory pediatric ependymoma who will receive either erlotinib or oral etoposide.

Inclusion Criteria:

- Recurrent of refractory ependymoma or subependymoma

- Performance Status (PS): Lansky >=50% for patients <=10 years of age or Karnofsky
>=50% for patients >10 years of age

- Measurable disease, defined as 1 measurable lesion that can be accurately measured in
2 planes that has not received radiation therapy within 12 weeks

- Recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or
radiotherapy

- >=1 year to <=21 years

- Serum creatinine for patients <=5 years in age is <=0.8 mg/dL or Creatinine
Clearance/Glomerular Filtration Rate (GFR) >=70 mL/min/m2

- Serum creatinine for patients >5 and <=10 years in age is <=1.0 mg/dL or Creatinine
Clearance/GFR >=70 mL/min/m2

- Serum creatinine for patients >10 and <=15 years in age is <=1.2 mg/dL or Creatinine
Clearance/GFR >=70 mL/min/m2

- Serum creatinine for patients >15 years in age is <=1.5 mg/dL or Creatinine
Clearance/GFR >=70 mL/min/m2

- Total bilirubin is <=1.5 x upper limit of normal for age

- Serum glutamic pyruvic transminase (SGPT) ALT <= 3 x upper limit of normal

- Absolute neutrophil count > 1000/µL

- Platelet count > 100,000/µL

- Hemoglobin > 8 gm/dL

- Neurologically stable for at least 7 days prior to randomization

- If receiving corticosteroids, patients must be on a stable or decreasing dose for at
least 7 days before randomization

- Patients of reproductive potential must agree to proactive effective contraceptive
measures for the duration of the study and for at least 90 days after completion of
study drug

Exclusion Criteria:

- Previously received epidermal growth factor receptor (EGFR)-targeted therapy

- Previously received oral etoposide

- Received craniospinal radiotherapy within 24 weeks prior to randomization

- Received field radiotherapy to the target lesion within 12 weeks prior to
randomization

- Received symptomatic metastatic disease within 14 days prior to randomization

- Received myelosuppressive chemotherapy within 21 days before randomization

- Received growth factors within 7 days prior to randomization

- Participating in another investigational drug trial

- Received a biologic agent within 7 days prior to randomization

- Received a monoclonal antibody within 28 days prior to randomization

- Taking CYP3A4 or CYP1A2 inhibitors/inducers within 14 days prior to randomization

- Taking proton pump inhibitors within 14 days prior to randomization

- Smoking during treatment

- Pregnant or breast-feeding females