Bevacizumab in Treating Young Patients With Refractory Solid Tumors

Inclusion Criteria:

• Histologically confirmed solid tumor at original diagnosis
• Measurable or evaluable* disease
• No known curative therapy exists
• No lymphomas or primary CNS tumors
• No history or clinical evidence of CNS metastasis by head CT scan
• Performance status - Karnofsky 50-100% (patients > 10 years of age)
• Performance status - Lansky 50-100% (patients ≤ 10 years of age)
• At least 8 weeks

• 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)
• PT or PTT ≤ 1.2 times upper limit of normal (ULN)
• ALT ≤ 5 times ULN
• Bilirubin ≤ 1.5 times ULN
• Albumin ≥ 2 g/dL
• Creatinine clearance or radioisotope glomerular filtrationrate ≥ 70 mL/min

• 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
• 24-hour urine protein ≤ 500 mg
• 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
• No pulmonary embolism within the past 3 months
• 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
• 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
• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
• No concurrent chemotherapy
• 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
• 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

• 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