ZD6474 Alone and in Combination With Retinoic Acid in Pediatric Neuroblastoma

Inclusion Criteria:

1. Provision of informed consent from subjects or their legal guardians
2. Patients must have had histologic verification of neuroblastoma, ganglioneuroblastoma, or ganglioneuroma, and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines (Vanillylmandelic Acid (VMA) and/or Homovanillic Acid (HVA)), OR histologic verification of medulloblastoma, AND which has progressed on standard therapy, relapsed after standard therapy, or for which no standard curative therapy is known.
3. Measurable or evaluable disease presence within 4 weeks of onset of study therapy: a. measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan or X-ray obtained prior to study entry. Patients who appear to have residual stable tumor upon completion of frontline therapy must undergo a biopsy to document presence of viable neuroblastoma or medulloblastoma. If only active target lesion was radiated of patients with stable disease, biopsy must be done at least 4 weeks after radiation was completed and must demonstrate viable tumor, OR
4. (Con't # 3): Evaluable disease documented by bone marrow obtained prior to study entry with tumor cells seen on routine morphology (not by Neuron Specific Enolase (NSE) staining only) of aspirate and/or biopsy OR
5. (Con't # 3) (for neuroblastoma patients only) Evaluable disease documented by MIBG (metaiodobenzylguanidine) scan or bone scan obtained within 4 weeks prior to study entry with positive uptake at a minimum of one site. Patients who appear to have residual stable MIBG positive lesions upon completion of frontline therapy must undergo a biopsy to document the presence of viable neuroblastoma. If the patient has only one MIBG positive lesion and that lesion was radiated, a biopsy must be done at least 4 weeks after radiation was completed and must demonstrate viable neuroblastoma.
6. Performance status - Lansky play or karnofsky score of > / = 40
7. Age >/=2 years at time of enrollment

Exclusion Criteria:

1. Lab results: a) Absolute neutrophil count (ANC) <750/mm^3, hemoglobin <7.0 g/dL, platelets <20,000/mm^3 (hemoglobin and platelets may be supported by transfusions); b) Serum bilirubin >1.5 * institutional upper limit of normal (IULN); c) Serum creatinine >1.5 * per IULN or creatinine clearance <or equal to 70 ml/min/1.73m^2; d) Potassium, <4.0 mmol/L despite supplement; Serum calcium or ionized calcium >IULN; Magnesium out of normal range per institutional guidelines despite supplement; e) ALT > 2.5 * IULN or alkaline phosphatase (ALP) >2.5 * IULN or > 5 * IULN if judged by the investigator to be related to liver metastases
2. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
3. History of symptomatic or medically managed arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) (>/= National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation controlled on medication is not excluded.
4. Previous history of Corrected QT (QTc) prolongation as a result from other medication that required discontinuation of that medication.
5. Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age.
6. Presence of left bundle branch block
7. QTc with Bazett's correction that is unmeasurable, or >/=480 msec on screening Electrocardiography (ECG). If a patient has QTc >/=480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the patient to be eligible for the study.
8. Use of any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
9. Clinically significant cardiac event such as myocardial infarction, TIA, or CVA within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
10. Hypertension > 95th percentile for age (either systolic or diastolic) or > 140/90 for patients >18 years of age and uncontrolled by oral medication at onset of study therapy.
11. Currently active diarrhea that may affect the ability of the patient to absorb the ZACTIMA.
12. Women who are currently pregnant or breastfeeding.
13. Receipt of any investigational agents within 14 days prior to commencing study treatment, or prior receipt of ZACTIMA at any time
14. Last dose of prior chemotherapy discontinued less than 2 weeks before the start of study therapy.
15. Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy to non-index lesions
16. Any unresolved non-hematologic toxicity greater than CTC grade 1 from previous anti-cancer therapy, except for platinum-induced hearing loss.
17. Any evidence of active graft versus host disease after stem cell transplant.
18. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy.