RATIONALE: Monoclonal antibodies, such as bevacizumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bevacizumab in treating young patients with refractory solid tumors.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of bevacizumab in pediatric patients with refractory solid tumors.
• Determine the dose-limiting toxicity and other toxic effects of this drug in these patients.
• Determine the pharmacokinetic behavior of this drug in these patients.

Secondary

• Determine, preliminarily, the antitumor activity of this drug in these patients.
• Determine the biologic activity of this drug at baseline and post-treatment in these patients.
• Determine the biologic effect of this drug on circulating endothelial cells and circulating endothelial cell precursors in these patients.
• Determine the expression of vascular endothelial growth factor by immunohistochemistry and/or real time polymerase chain reaction in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 1-8 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor at original diagnosis
• Measurable or evaluable* disease NOTE: *Defined as a tumor that cannot be quantified using a ruler or calipers, but can be used to determine disease progression or complete response (e.g., disease detectable by bone scan, metaiodobetaguanidine [MIBG] scan, bone marrow disease, tumor marker, or presence of malignant pleural effusion)
• No known curative therapy exists
• No lymphomas or primary CNS tumors
• No history or clinical evidence of CNS metastasis by head CT scan

PATIENT CHARACTERISTICS:

Age

• 1 to 21

Performance status

• Karnofsky 50-100% (patients > 10 years of age) OR
• Lansky 50-100% (patients ≤ 10 years of age)

Life expectancy

• At least 8 weeks

Hematopoietic

• Patients without bone marrow involvement:

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed)

• Patients with bone marrow metastases:

  • Platelet count ≥ 75,000/mm^3 (transfusion independent)
  • Granulocytopenia, anemia, and/or mild thrombocytopenia allowed
• No known bleeding diathesis or coagulopathy
• No known thrombophilic condition (e.g., protein S, protein C, or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocystinemia, or antiphospholipid antibody syndrome)

Hepatic

• PT or PTT ≤ 1.2 times upper limit of normal (ULN)
• ALT ≤ 5 times ULN
• Bilirubin ≤ 1.5 times ULN
• Albumin ≥ 2 g/dL

Renal

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR

• Creatinine based on age as follows:

  • Creatinine ≤ 0.8 mg/dL (patients ≤ 5 years of age)
  • Creatinine ≤ 1.0 mg/dL (patients 6 to 10 years of age)
  • Creatinine ≤ 1.2 mg/dL (patients 11 to 15 years of age)
  • Creatinine ≤ 1.5 mg/dL (patients > 15 years of age)
• No proteinuria OR
• 24-hour urine protein ≤ 500 mg

Cardiovascular

• No history of stroke
• No deep venous or arterial thrombosis within the past 3 months

• No uncontrolled hypertension

  • Hypertension must be well-controlled with stable doses of medication for at least 2 weeks
• No history of myocardial infarction
• No severe or unstable angina
• No transient ischemic attack within the past 6 months
• No cerebrovascular accident within the past 6 months
• No other arterial thromboembolic event within the past 6 months
• No clinically significant or severe peripheral vascular disease

Pulmonary

• No pulmonary embolism within the past 3 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study participation
• No chronic non-healing wound, ulcer, or bone fracture
• No significant traumatic injury within the past 28 days
• No uncontrolled seizures
• No uncontrolled infection
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Recovered from prior immunotherapy
• More than 1 week since prior growth factors

• At least 2 months since prior stem cell transplantation

  • No evidence of active graft-vs-host disease
• At least 8 weeks since prior monoclonal antibody therapy
• At least 7 days since prior antineoplastic biologic agents
• No prior bevacizumab
• No concurrent prophylactic growth factors
• No other concurrent immunotherapy or biologic therapy

Chemotherapy

• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Recovered from prior radiotherapy
• At least 4 months since prior craniospinal radiotherapy
• At least 4 months since prior radiotherapy to ≥ 50% of the pelvis
• At least 6 weeks since other prior substantial bone marrow radiotherapy
• At least 2 weeks since prior local palliative small-port radiotherapy
• No concurrent radiotherapy

Surgery

• More than 28 days since prior major surgery
• At least 7 days since prior minor surgery (for limited purposes of tissue retrieval) and recovered
• At least 24 hours since prior placement of an indwelling IV catheter

Other

• At least 1 week since prior full-dose anticoagulation therapy, including systemic thrombolytic agents, heparin, low-molecular weight heparin, and warfarin

  • Local intralumenal anticoagulants (e.g., heparin or tissue plasminogen activator) allowed to maintain patency of preexisting, permanent, indwelling IV catheters or peripheral IV catheters for blood sampling
• More than 1 week since prior antipyretic and anti-inflammatory medications (except acetaminophen)
• No concurrent full-dose anticoagulation therapy
• No concurrent anti-inflammatory medication
• Concurrent acetaminophen allowed
• No other concurrent cancer therapy
• No other concurrent investigational agents