Sunitinib in Treating Young Patients With Refractory Solid Tumors

Inclusion Criteria:

• Histologically confirmed solid tumor (not required for patients with intrinsic brain stem tumors or optic pathway gliomas)

  • Recurrent or refractory disease
• Measurable or evaluable disease
• No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists

• Patients with metastatic bone marrow disease are eligible but are not evaluable for hematologic toxicity

  • Must not be refractory to red blood cell or platelet transfusions

• Primary CNS tumors or known CNS metastases allowed

  • Neurological deficits must have been relatively stable for ≥ 1 week before study enrollment
  • No imaging evidence of prior intracranial hemorrhage

  • No evidence of new CNS hemorrhage on baseline MRI obtained within 14 days before study enrollment (ECHO gradient MRI sequences per institutional guidelines required for evaluation of CNS hemorrhage)

    • The presence of small punctuate CNS hemorrhage on these scans will exclude a patient from participation
• No known bone marrow metastatic disease
• No tumors involving the pleural surface
• Karnofsky performance status (PS) 50-100% (> 10 years of age) OR Lansky PS 50-100% (≤ 10 years of age)
• Absolute neutrophil count ≥ 1,000/mm³*
• Platelet count ≥ 100,000/mm³ (transfusion independent)*
• Hemoglobin ≥ 8.0 g/dL (transfusions allowed)*

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age/gender as follows:

  • No greater than 0.8 mg/dL (2 to 5 years of age)
  • No greater than 1 mg/dL (6 to 9 years of age)
  • No greater than 1.2 mg/dL (10 to 12 years of age)
  • No greater than 1.5 mg/dL (male) OR 1.4 mg/dL (female) (13 to 15 years of age)
  • No greater than 1.7 mg/dL (male) OR 1.4 mg/dL (female) (≥ 16 years of age)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)
• Albumin ≥ 2 g/dL
• LVEF or shortening fraction normal
• Corrected QT interval ≤ 450 msec
• Amylase ≤ 1.5 times ULN
• Lipase ≤ 1.5 times ULN
• Body surface area ≥ 0.5 m² (≥ 0.4 m² for part B)
• Blood pressure within ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No uncontrolled infection
• Able to swallow sunitinib malate capsules (part A only)
• No pre-existing thyroid abnormality (hyper- or hypothyroidism) with unstable thyroid function
• No prior CNS hemorrhage
• No history of allergic reaction attributed to sunitinib malate or component of sunitinib malate capsules
• No allergy to both applesauce and yogurt (part B only)
• Recovered from prior therapy
• No prior sunitinib malate
• No prior anthracycline (any dose)
• No prior radiotherapy to a radiation field that included the heart(including total body or craniospinal irradiation)
• At least 3 months since prior stem cell transplantation or rescue (without total-body irradiation) and no evidence of graft-vs-host disease
• At least 2 weeks since prior local, palliative, small-port radiotherapy (at least 6 months for radiation to ≥ 50% of pelvis)
• At least 6 weeks since other prior substantial bone marrow radiotherapy
• At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosoureas)
• At least 1 week since prior antineoplastic biologic agents
• At least 1 week since prior and no concurrent hematopoietic growth factors

• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

  • Rifampin
  • Rifabutin
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • Hypericum perforatum (St. John's wort)
  • Efavirenz
  • Tipranavir

• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

  • Azole antifungals (e.g., itraconazole or ketoconazole)
  • Clarithromycin
  • Erythromycin
  • Diltiazem
  • Verapamil
  • HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir)
  • Delavirdine
• No more than 1 concurrent antihypertensive agent
• No concurrent major surgery

• No concurrent antithrombotic or antiplatelet agents, including any of the following:

  • Warfarin
  • Heparin
  • Low molecular weight heparin
  • Acetylsalicylic acid (aspirin)
  • Ibuprofen
  • Other nonsteroidal anti-inflammatory drugs
• No concurrent medication for the treatment of hypertension
• No other concurrent investigational drugs
• No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy