Full Text View
Tabular View
No Study Results Posted
Related Studies
Cilengitide in Treating Children With Refractory Primary Brain Tumors
This study has been completed.

First Received on July 8, 2003.   Last Updated on October 23, 2009   History of Changes
Sponsor: Pediatric Brain Tumor Consortium
Collaborator: National Cancer Institute (NCI)
Information provided by: Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT00063973
  Purpose

RATIONALE: Cilengitide may slow the growth of brain cancer cells by stopping blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of cilengitide in treating children with recurrent, progressive, or refractory primary CNS tumors.


Condition Intervention Phase
Brain and Central Nervous System Tumors
 Drug: cilengitide
 Phase I

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: Phase I Study of Cilengitide (EMD 121974) in Children With Refractory Brain Tumors

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer Childhood Brain Tumors
Drug Information available for: Cilengitide
U.S. FDA Resources

Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:
  • Acute and dose-limiting toxicities [ Designated as safety issue: Yes ]
  • Maximum tolerated dose [ Time Frame: First four weeks of therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Correlation of imaging parameters (tissue perfusion, tumor blood flow, and metabolic activity as measured by MR perfusion, PET, and MRS) with tumor size as measured by volumetric MRI [ Designated as safety issue: No ]
  • Pharmacokinetics [ Designated as safety issue: No ]
  • Correlation of circulating endothelial cells and circulating endothelial precursors with angiogenic protein levels and outcome [ Designated as safety issue: No ]
  • Efficacy [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: July 2003
Study Completion Date: March 2008
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the acute and dose-limiting toxic effects of cilengitide (EMD 121974) in children with refractory primary brain tumors.
  • Determine the maximum tolerated dose of this drug in these patients.
  • Correlate tissue perfusion, tumor blood flow and metabolic activity using MR perfusion, PET and MRS with changes in tumor size by volumetric MRI
  • Determine the inter- and intra-patient variability in the pharmacokinetics of this drug and estimate its renal clearance in these patients.
  • Correlate the changes in circulating endothelial cells and circulating endothelial precursors with plasma, serum, and urine angiogenic protein levels and with clinical outcome in patients treated with this drug.
  • Determine, preliminarily, the efficacy of this drug in these patients.

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

Patients receive cilengitide (EMD 121974) IV over 1 hour twice weekly. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of cilengitide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients are expected to experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients are accrued and treated at that dose level for a total of 12 patients at the MTD.

Patients receiving treatment are followed weekly for the first three months then monthly for one year or 13 courses of treatment. Patients discontinuing treatment will be followed for resolution of all adverse events occurring while on treatment and/or within 30 days of the last administration of study drug. Patients will be followed for the shortest of 1) three months after the last protocol based treatment, or 2) the date other therapy is initiated.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 1-1.5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary central nervous system (CNS) tumor, including histologically benign CNS tumors (e.g., low-grade gliomas)*

    • Recurrent or progressive disease
    • Refractory to standard therapy NOTE: *In the absence of histological diagnosis, clinical and radiographic evidence of a brain stem or optic pathway glioma is required
  • Patients with bone marrow involvement may be eligible

PATIENT CHARACTERISTICS:

Age

  • 21 and under

Performance status

  • Karnofsky 50-100% OR
  • Lansky 50-100%

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count greater than 1,000/mm^3
  • Platelet count greater than 100,000/mm^3 (transfusion independent)
  • Hemoglobin greater than 8.0 g/dL (transfusion allowed)

Hepatic

  • Bilirubin normal
  • ALT and AST less than 2.5 times upper limit of normal
  • No overt hepatic disease

Renal

  • Creatinine less than 1.5 times normal OR
  • Glomerular filtration rate greater than 70 mL/min
  • No overt renal disease

Cardiovascular

  • No overt cardiac disease

Pulmonary

  • No overt pulmonary disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Neurological deficits allowed provided that they are stable for at least 1 week before study entry
  • No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 1 week since prior growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
  • More than 6 months since prior bone marrow transplantation
  • More than 2 weeks since prior biological agents

Chemotherapy

  • At least 6 weeks since prior nitrosoureas

Endocrine therapy

  • Concurrent corticosteroids allowed provided that they are at a stable dose for at least 1 week before study entry

Radiotherapy

  • At least 6 weeks since prior radiotherapy
  • More than 2 weeks since prior local palliative radiotherapy
  • More than 3 months since prior craniospinal (more than 24 Gy) or total body radiotherapy

Surgery

  • Not specified

Other

  • Recovered from prior therapy
  • More than 2 weeks since prior investigational agents
  • At least 4 weeks since prior myelosuppressive therapy
  • Concurrent anticonvulsants allowed
  • No other concurrent anticancer agents or therapies
  • No other concurrent experimental agents or therapies
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00063973

Locations
United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Investigators
Study Chair: Tobey MacDonald, MD Children's Research Institute
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:
MacDonald TJ, Stewart CF, Kocak M, Goldman S, Ellenbogen RG, Phillips P, Lafond D, Poussaint TY, Kieran MW, Boyett JM, Kun LE. Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012. J Clin Oncol. 2008 Feb 20;26(6):919-24.

Responsible Party: James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT00063973     History of Changes
Other Study ID Numbers: CDR0000305859, PBTC-012
Study First Received: July 8, 2003
Last Updated: October 23, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Pediatric Brain Tumor Consortium:
recurrent childhood brain stem glioma
recurrent childhood brain tumor
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
 recurrent childhood ependymoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway and hypothalamic glioma
childhood central nervous system germ cell tumor
childhood choroid plexus tumor
childhood craniopharyngioma
childhood oligodendroglioma

Additional relevant MeSH terms:
Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
 Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on February 12, 2012



Contact Help Desk
Lister Hill National Center for Biomedical Communications,  U.S. National Library of Medicine,
U.S. National Institutes of Health,  U.S. Department of Health & Human Services,
USA.gov,  Copyright,  Privacy,  Accessibility,  Freedom of Information Act

U.S. National Institutes of Health U.S. National Library of Medicine U.S. Department of Health & Human Services