INCLUSION CRITERIA:
1) Age: Patients must be greater than 12 months and less than or equal to 21 years of age at the time of study enrollment.
2) Diagnosis: Patients must have had histologic verification of malignancy at original diagnosis or relapse (excluding intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of serum alpha-fetoprotein of beta-HCG). Patients with recurrent or refractory solid tumors are eligible, including primary CNS tumors or patients with known CNS metastases.
3) Disease Status: Patients must have either measurable or evaluable disease.
4) Therapeutic Options: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
5) Performance Level: Karnofsky greater than or equal to 50% for patients older than 16 years of age and Lansky greater than or equal to 50 for patients less than or equal to 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 1 week prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
6) Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
a) Myelosuppressive chemotherapy: Must not have received within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
b) Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor.
c) Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. At least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
d) XRT: greater than or equal to 2 wks for local palliative XRT (small port); greater than equal to 3 months must have elapsed if prior TBI, craniospinal XRT or if greater than or equal to 50% radiation of pelvis; greater than or equal to 6 wks must have elapsed if other substantial BM radiation.
e) Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and greater than 2 months must have elapsed since transplant.
7) Organ Function Requirements:
Adequate Bone Marrow Function defined as:
a. For patients with solid tumors without bone marrow involvement:
1) Peripheral absolute neutrophil count (ANC) greater than or equal to 1000/microL
2) Platelet count greater than or equal to 100,000/microL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
3) Hemoglobin greater than or equal to 8.0 g/dL (may receive RBC transfusions)
b. Patients with known bone marrow metastatic disease will be eligible for study but not evaluated for hematologic toxicity. These patients must not be known to be refractory to red cell or platelet transfusion. At least 2 of every cohort of 3 patients must be evaluable for hematologic toxicity. If dose limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.
Adequate Renal Function Defined as:
a) Negative protein dipstick or less than 500 mg protein/24 hour urine collection
b) Creatinine clearance or radioisotope GFR greater than or equal to 70mL/min/1.73 m(2) or serum creatinine based on age/gender as follows:
1 to less than 2 years of age, male: 0.6; female: 0.6 maximum serum creatinine (mg/dL)
2 to less than 6 years of age, male: 0.8, female: 0.8 maximum serum creatinine (mg/dL)
6 to less than 10 years or age, male: 1, female: 1 maximum serum creatinine (mg/dL)
10 to less than 13 years of age, male: 1.2, female: 1.2 maximum serum creatinine (mg/dL)
13 to less than 16 years of age, male: 1.5, female: 1.4 maximum serum creatinine (mg/dL)
Greater than or equal to 16 years of age, male: 1.7, female: 1.4 maximum serum creatinine (mg/dL)
Adequate Liver Function Defined As:
a) Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 times the upper limit of normal (ULN) for age
b) SGPT (ALT) less than or equal to 110 U/L (approx. 2.5 times ULN). For the purpose of this study, the ULN for SGPT is 45 U/L
c) Serum albumin greater than or equal to 2 g/dL.
Adequate Blood Clotting Defines As:
a) PT/aPTT less than1.2 times the upper limit of normal
Blood Pressure
a) Patients must have a blood pressure (BP) less than or equal to the 95th percentile for age, height, and gender, and not be receiving medication for treatment of hypertension.
8) Informed Consent: All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
EXCLUSION CRITERIA:
1) Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
2) Concomitant Medications:
a) Growth factor(s): Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment.
b) Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days.
c) Investigational Drugs: Patients who are currently receiving another investigational drug.
d) Anti-cancer Agents: Patients who are currently receiving other anticancer agents.
e) Antihypertensives: Patients who are currently receiving medication(s) for blood pressure control.
f) Anti-thrombotic and anti-platelet agents: warfarin (coumadin ® (Registered Trademark)), heparin, low molecular weight heparin, aspirin, and/or ibuprofen, or other NSAIDs.
3) Infection: Patients who have an uncontrolled infection.
4) CNS disease: Evidence of CNS hemorrhage based upon baseline MRI obtained within 14 days prior to study enrollment.
5) Surgery: Patients who have had or are planning to have the following invasive procedures:
a) Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy. Subcutaneous port placement or central line placement is not considered major surgery but must be placed greater than 48 hours from planned Day 1 of therapy.
b) Core biopsy within 7 days prior to Day 1 therapy.
c) Fine needle aspirate or central line placement within 48 hours prior to Day 1 therapy.
6) Patients with serious or non-healing wound, ulcer, or bone fracture.
7) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
8) Patients with clinically significant cardiovascular disease (any of the following):
a) History of CVA within past 6 months, or
b) New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months, or
c) Pulmonary embolism, DVT, or other thromboembolic event within past 6 months.
9) Patients with evidence of a current bleeding diathesis or coagulopathy.
10) Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, and patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to VEGF Trap.
11) Patients who have previously received study drug.
12) Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.