A Phase I Study of VEGF Trap (NSC# 724770, IND# 100137) in Children With Refractory Solid Tumors
Inclusion Criteria:
- Histologically confirmed 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
- 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
- Measurable or evaluable disease
- No evidence of CNS hemorrhage on baseline MRI for patients with known CNS disease
- Karnofsky performance status (PS) 50-100% (for patients > 10 years of age) or Lansky
PS 50-100% (for patients ≤ 10 years of age)
- Neurologic deficits in patients with CNS tumors must have been relatively stable
for a minimum of 1 week prior to study entry
- 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
- Patients with solid tumors without bone marrow involvement must meet the following
criteria:
- ANC ≥ 1,000/mm³
- Platelet count ≥ 100,000/mm³ (transfusion independent, defined as not receiving
platelet transfusions within a 7 day period prior to enrollment)
- Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
- Negative protein dipstick OR urine protein < 500 mg by 24-hour urine collection
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum
creatinine based on age/gender as follows:
- 0.6 mg/dL for male and female patients 1 to < 2 years of age
- 0.8 mg/dL for male and female patients 2 to < 6 years of age
- 1.0 mg/dL for male and female patients 6 to < 10 years of age
- 1.2 mg/dL for male and female patients 10 to < 13 years of age
- 1.5 mg/dL (male) or 1.4 mg/dL (female) for patients 13 to < 16 years of age
- 1.7 mg/dL (male) or 1.4 mg/dL (female) for patients ≥ 16 years of age
- Bilirubin ≤ 1.5 times upper limit of normal (U.N.) for age
- SEPT (ALT) ≤ 110 μ/L (approx. 2.5 times U.N.) (for the purpose of this study, the
U.N. for SEPT is 45 μ/L)
- Serum albumin ≥ 2 g/dL
- PT/aPTT < 1.2 times U.N.
- Patients must have a diastolic blood pressure ≤ the 95th percentile for age and
gender and not be receiving treatment for hypertension
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of active graft-vs-host disease
- No uncontrolled infection
- No serious or nonhealing wound, ulcer, or bone fracture
- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 4 weeks prior to day 1 of study treatment
- No clinically significant cardiovascular disease within the past 6 months, including
any of the following:
- History of cerebrovascular accident
- New York Heart Association class III-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Unstable angina pectoris
- Pulmonary embolism
- Deep vein thrombosis
- Other thromboembolic events
- No evidence of a current bleeding diathesis or coagulopathy
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to other agents used in the study
- No significant traumatic injury within 4 weeks prior to day 1 of study treatment
- Must be able to comply with the safety monitoring requirements of the study in the
opinion of the investigator
- Recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or
radiotherapy
- No prior aflibercept
- At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
- At least 6 weeks since prior monoclonal antibodies
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 6 weeks since other prior substantial bone marrow radiotherapy
- At least 2 months since prior stem cell transplantation or rescue
- At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or
radiotherapy to ≥ 50% of the pelvis
- At least 4 weeks since prior major surgical procedure, laparoscopic procedure, or
open biopsy and no anticipation of need for major surgical procedures during the
course of the study
- At least 48 hours since prior fine needle aspirate, central line placement, or
subcutaneous port placement
- At least 1 week since prior core biopsy
- At least 1 week since prior and no concurrent hematopoietic growth factors
- At least 1 week since prior and no concurrent biologic agents
- At least 1 week since prior and no concurrent dexamethasone
- No concurrent antihypertensive medications for blood pressure control
- No concurrent anti-thrombotic or anti-platelet agents (e.g., warfarin [Coumadin
®],heparin, low molecular weight heparin, aspirin, and/or ibuprofen, or other NSAIDs)
- No concurrent medications known to inhibit platelet function or known to selectively
inhibit cyclooxygenase-2 activity (e.g., all antipyretic and anti-inflammatory
medications except acetaminophen)
- No other concurrent anticancer therapy, including chemotherapy, radiotherapy,
immunotherapy, or biologic therapy
- No other concurrent investigational drugs