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Aflibercept in Treating Young Patients With Relapsed or Refractory Solid Tumors
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), May 2008
First Received: February 22, 2008   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: Children's Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00622414
  Purpose

RATIONALE: Aflibercept may stop the growth of tumor cells by blocking blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of aflibercept in treating young patients with relapsed or refractory solid tumors.


Condition Intervention Phase
Unspecified Childhood Solid Tumor, Protocol Specific
Biological: aflibercept
Phase I

MedlinePlus related topics: Cancer
Drug Information available for: Aflibercept
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of VEGF Trap (NSC# 724770, IND# 100137) in Children With Refractory Solid Tumors

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose or recommended phase II dose [ Designated as safety issue: Yes ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antitumor activity [ Designated as safety issue: No ]

Estimated Enrollment: 27
Study Start Date: April 2008
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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.
  • To estimate the MTD or RPTD of aflibercept administered intravenously every 21 days in these patients.
  • To define and describe the toxicities of intravenous aflibercept administered on a 14-day and 21-day schedule, respectively.
  • To characterize the pharmacokinetics of intravenous aflibercept in these patients.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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) NOTE: *Patients with known bone marrow metastatic disease are eligible but not evaluated for hematologic toxicity; they also must not be known to be refractory to red cell or platelet transfusion
  • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00622414

Locations
United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Clinical Trials Office - Lurleen Wallace Comprehensive Cancer     205-934-0309        
United States, California
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Violet Shen     714-532-8636        
United States, Illinois
Children's Memorial Hospital - Chicago Recruiting
Chicago, Illinois, United States, 60614
Contact: David O. Walterhouse     773-755-6514        
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202-5289
Contact: Clinical Trials Office - Indiana University Cancer Center     317-274-2552        
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Clinical Trials Office - Cincinnati Children's Hospital Medica     513-636-0161        
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Clinical Trials Office - St. Jude Children's Research Hospital     901-595-4644        
United States, Texas
Baylor University Medical Center - Houston Recruiting
Houston, Texas, United States, 77030-2399
Contact: Alberto Pappo     832-822-4248        
United States, Washington
Children's Hospital and Regional Medical Center - Seattle Recruiting
Seattle, Washington, United States, 98105
Contact: Douglas Hawkins     206-987-3096        
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Julie R. Park, MD Seattle Children's Hospital
Principal Investigator: Elizabeth Fox, MD NCI - Pediatric Oncology Branch
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000584050, COG-ADVL0714, NCI-08-C-0179, NCI-P08401
Study First Received: February 22, 2008
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00622414     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific

ClinicalTrials.gov processed this record on March 13, 2009