This phase I trial is studying the side effects and best dose of AZD2171 in treating young patients with recurrent, progressive, or refractory primary CNS tumors. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of AZD2171 in pediatric patients with recurrent, progressive, or refractory primary CNS tumors.

II. Describe the toxicity profile and dose-limiting toxicities of AZD2171 in these patients.

SECONDARY OBJECTIVES:

I. Characterize inter-patient variability in the pharmacokinetics of AZD2171 in these patients.

II. Describe changes in circulating endothelial cells (CECs) and circulating endothelial cell precursors (CEPs) in patients treated with AZD2171 at different dose levels.

III. Correlate changes in CECs, CEPs, plasma, serum, and urine levels of proteins with angiogenesis, including vascular endothelial growth factor (VEGF) and VEGF receptor, in patients treated with AZD2171 at different dose levels.

IV. Correlate changes in CECs, CEPs, and angiogenic modulators with changes in magnetic resonance (MR) perfusion.

V. Obtain preliminary evidence of biologic activity of AZD2171 by evaluating alterations in tissue perfusion, tumor blood flow, and metabolic activity using MR perfusion and diffusion imaging, and positron-emission tomography, and correlating these findings with changes in tumor size by standard MRI.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent enzyme-inducing anticonvulsant drugs (yes vs no).

Patients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

For each stratum, cohorts of 2-6 patients receive escalating doses of AZD2171 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients per stratum are enrolled and treated at the MTD.

After completion of study, patients are followed at 30 days.

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