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Bevacizumab in Treating Young Patients With Refractory Solid Tumors
This study has been completed.
First Received: June 10, 2004   Last Updated: February 6, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00085111
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

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


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

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study Of Bevacizumab In Refractory Solid Tumors

Resource links provided by NLM:


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

Study Start Date: December 2003
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of bevacizumab in pediatric patients with refractory solid tumors.
  • Determine the dose-limiting toxicity and other toxic effects of this drug in these patients.
  • Determine the pharmacokinetic behavior of this drug in these patients.

Secondary

  • Determine, preliminarily, the antitumor activity of this drug in these patients.
  • Determine the biologic activity of this drug at baseline and post-treatment in these patients.
  • Determine the biologic effect of this drug on circulating endothelial cells and circulating endothelial cell precursors in these patients.
  • Determine the expression of vascular endothelial growth factor by immunohistochemistry and/or real time polymerase chain reaction in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 1-8 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor at original diagnosis
  • Measurable or evaluable* disease NOTE: *Defined as a tumor that cannot be quantified using a ruler or calipers, but can be used to determine disease progression or complete response (e.g., disease detectable by bone scan, metaiodobetaguanidine [MIBG] scan, bone marrow disease, tumor marker, or presence of malignant pleural effusion)
  • No known curative therapy exists
  • No lymphomas or primary CNS tumors
  • No history or clinical evidence of CNS metastasis by head CT scan

PATIENT CHARACTERISTICS:

Age

  • 1 to 21

Performance status

  • Karnofsky 50-100% (patients > 10 years of age) OR
  • Lansky 50-100% (patients ≤ 10 years of age)

Life expectancy

  • At least 8 weeks

Hematopoietic

  • 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)

Hepatic

  • PT or PTT ≤ 1.2 times upper limit of normal (ULN)
  • ALT ≤ 5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • Albumin ≥ 2 g/dL

Renal

  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
  • 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 OR
  • 24-hour urine protein ≤ 500 mg

Cardiovascular

  • 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

Pulmonary

  • No pulmonary embolism within the past 3 months

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • 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

Chemotherapy

  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
  • No concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • 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

Surgery

  • 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

Other

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00085111

  Hide Study Locations
Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61637
United States, Indiana
Riley Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States, 46202-5225
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
University Hospital at State University of New York - Upstate Medical University
Syracuse, New York, United States, 13210
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Oregon
Doernbecher Children's Hospital at Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213-2583
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
MBCCOP - South Texas Pediatrics
San Antonio, Texas, United States, 78229-3900
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390-9063
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Julia L. Glade-Bender, MD Herbert Irving Comprehensive Cancer Center
Investigator: Darrell J. Yamashiro, MD, PhD Herbert Irving Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000367299, COG-ADVL0314, NCI-04-C-0148
Study First Received: June 10, 2004
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00085111     History of Changes
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Neoplasms
Antineoplastic Agents
Therapeutic Uses
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Angiogenesis Modulating Agents
Bevacizumab
Angiogenesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2009