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A Phase I Study of VEGF Trap (NSC# 724770, IND# 100137) in Children With Refractory Solid Tumors

Phase 1
1 Year
21 Years
Not Enrolling
Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of VEGF Trap (NSC# 724770, IND# 100137) in Children With Refractory Solid Tumors


I. To estimate the maximum tolerated dose (MTD) or recommended phase II dose (RPTD) of
aflibercept administered intravenously every 14 days in children with relapsed or refractory
solid tumors.

II. To estimate the MTD or RPTD of aflibercept administered intravenously every 21 days in
these patients.

III. To define and describe the toxicities of intravenous aflibercept administered on a
14-day and 21-day schedule, respectively.

IV. To characterize the pharmacokinetics of intravenous aflibercept in these patients.


I. To define, preliminarily, the antitumor activity of intravenous aflibercept within the
confines of a phase I study.

OUTLINE: This is a multicenter study.

PART 1: Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 14
days for 2 years in the absence of disease progression or unacceptable toxicity. Cohorts of
3-6 patients receive aflibercept until the maximum tolerated dose (MTD) is determined.

PART 2: Patients receive aflibercept as in part 1 at 150% of the MTD determined in part 1.
Treatment repeats every 21 days for 2 years in the absence of disease progression or
unacceptable toxicity.

Blood samples are collected prior to treatment on day 1 of courses 1, 2, and 5 or 6 for
pharmacokinetic studies.

After completion of study treatment, patients are followed for at least 30 days.

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose, defined as the maximum dose at which fewer than one-third of patients experience DLT during the initial 2 courses of therapy, graded according to NCI CTCAE version 3.0

Outcome Time Frame:

Up to 28 days

Safety Issue:


Principal Investigator

Elizabeth Fox

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

April 2008

Completion Date:

Related Keywords:

  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Neoplasms



Baylor College of Medicine Houston, Texas  77030
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Oregon Health and Science University Portland, Oregon  97201
Seattle Children's Hospital Seattle, Washington  98105
Childrens Memorial Hospital Chicago, Illinois  60614
Columbia University Medical Center New York, New York  10032