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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

  Show 21 Study Locations
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 30, 2009