A Phase I Study of Bevacizumab in Refractory Solid Tumors

Fecha de inicio: 1 de diciembre de 2003

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