AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors

Inclusion Criteria:

• Histologically confirmed primary CNS tumor

  • Histologically benign brain tumors (e.g., low-grade glioma) allowed
  • Histological requirement waived for intrinsic brain stem or diffuse optic pathway tumors, but must have clinical and/or radiographic evidence of progression
• Recurrent, progressive, or refractory disease
• Absolute neutrophil count >= 1,000/mm^3 (unsupported)
• Platelet count >= 75,000/mm^3 (unsupported)
• Creatinine =< 1.5 times upper limit of normal (ULN) OR glomerular filtration rate >= 70 mL/min
• Bilirubin =< 1.5 times ULN
• ALT =< 2.5 times ULN
• Urine dipstick or urinalysis < 1+ protein
• Albumin >= 3 g/dL
• Karnofsky performance status (PS) 60-100% (> 16 years of age) OR Lansky PS 60-100% (=< 16 years of age)
• Karnofsky/Lansky PS 70-100% for patients at increased risk for compromised LVEF
• Hemoglobin >= 8 g/dL (transfusion support allowed)
• No overt renal, hepatic, cardiac, or pulmonary disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• QTc prolongation =< 500 msec
• No other significant ECG abnormality within the past 14 days
• No clinically significant, unrelated, systemic illness, including serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction, that would preclude study participation

• No uncontrolled hypertension

  • Defined as systolic and diastolic BP > 95th percentile for age (ages 1-17)
  • Defined as BP > 140/90 (ages 18 and older)

• No New York Heart Association class III or IV disease and Karnofsky/Lansky PS < 70

  • Class II disease controlled with treatment and increased monitoring is allowed
• Recovered from all prior therapy
• No prior AZD2171
• At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas)

• More than 1 weeks since prior investigational or biologic agents

  • If the investigational or biologic agent has a prolonged half-life (> 48 hours), then these patients must be discussed with the study chair prior to registration
• No concurrent drugs or biologics with proarrhythmic potential
• More than 3 months since last fraction of craniospinal radiotherapy or total-body irradiation
• More than 4 weeks since last fraction of focal irradiation to symptomatic metastatic sites
• At least 6 months since prior allogeneic bone marrow transplantation
• At least 3 months since prior autologous bone marrow or stem cell transplantation
• At least 1 week since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa (2 weeks for pegfilgrastim)
• No other concurrent investigational agents
• Concurrent dexamethasone allowed provided patient is on a stable or decreasing dose for ≥ 1 week before study entry
• No concurrent chemotherapy
• No concurrent routine use of G-CSF, GM-CSF, or epoetin alfa
• Able to swallow tablets
• Any neurologic deficits must be stable for >= 1 week
• If the investigational or biologic agent has a prolonged half-life (> 48 hours), then these patients must be discussed with the study chair prior to registration

Exclusion Criteria:

• No known curative therapy available