• Age: Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.

• Diagnosis: Patients with histologically-confirmed adamantinomatous craniopharyngioma (ACP) Histologic confirmation of ACP may be made on solid tumor or, if no solid tumor can be safely obtained, cyst fluid with classic ACP characteristics of thick, cholesterol-rich, greenish-brown liquid in the context of imaging features consistent with craniopharyngioma, including lobulated, cystic/solid mass with calcifications that originates in the sellar/suprasellar region.

• Disease Status: Patients must have measurable disease.

‣ Stratum 1: Patients with progressive or recurrent ACP who demonstrate cystic and/or solid recurrence or progression at least 6 months post completion of radiation therapy

⁃ Stratum 2: Patients with measurable ACP who have undergone surgery but have NOT previously undergone irradiation (but may have received prior systemic or intracystic therapy). Progressive disease is allowed but not required.

• Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

• Prior Therapy: Patients must have recovered or stabilized from the acute toxic effects of prior treatments

‣ Biologic (anti-neoplastic agent): At least 7 days must have elapsed after the last (systemic or intracystic) dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair

⁃ Immunotherapy: At least 42 days after the completion of any type of systemic immunotherapy, e.g. tumor vaccines.

⁃ Monoclonal antibodies: At least 21 days after the last dose of a monoclonal antibody.

⁃ Radiation therapy: Patients must have had their last (conventional or hypofractionated) fraction of: a) Focal irradiation \> 6 months prior to enrollment and b) No prior craniospinal irradiation is permitted.

⁃ Corticosteroids: Patients receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment

⁃ Myelosuppressive systemic therapy: At least 21 days must have elapsed after the last systemic myelosuppressive therapy.

⁃ Surgery: At least 6 weeks must have elapsed since major or intermediate surgery. Major surgery includes major craniotomy for tumor resection or cyst fenestration, organ resection, exploratory laparotomy. Intermediate procedures include ventriculoperitoneal shunt placement, stereotactic brain biopsy and intraventricular catheter placement. Minor procedures that are not excluded include skin biopsy/incision and drainage, bone marrow aspirate, and central venous catheter placement. Ommaya aspirations and Lumbar Punctures are considered minor procedures..

• Organ Function Requirements

• Adequate Bone Marrow Function Defined as:

⁃ Peripheral absolute neutrophil count (ANC) ≥1000/mm3

⁃ Platelet count ≥100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

⁃ Hemoglobin \>8 g/dL (may be transfused)

• Adequate Renal Function Defined as:

⁃ Creatinine clearance or radioisotope GFR \> 70ml/min/1.73 m2 or

⁃ A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows:

‣ 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to \< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females.

‣ ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females.

• Adequate Liver Function Defined as:

⁃ Total bilirubin within normal institutional limits

⁃ AST (SGOT) ≤ 2.5 × institutional upper limit of normal

⁃ ALT (SGPT) ≤ 2.5 × institutional upper limit of normal

• Adequate Neurologic Function Defined as:

⁃ Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment.

⁃ Patients with current seizure disorders may be enrolled if seizures are well-controlled on antiepileptic therapies.

• Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.