Cilengitide in Treating Children With Refractory Primary Brain Tumors - Full Text View

Sponsors and Collaborators:	Pediatric Brain Tumor Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
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:	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 National Cancer Institute (NCI):

Study Start Date:	July 2003
Primary Completion Date:	March 2008 (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.
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 angiogeneic protein levels and with clinical outcome in patients treated with this drug.
Determine, preliminarily, the efficacy and biologic activity 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.

Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually for 5 years.

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, 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, 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.

Study ID Numbers:	CDR0000305859, PBTC-012
Study First Received:	July 8, 2003
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00063973 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Choroid Plexus Neoplasms
Neuroectodermal Tumors, Primitive
Astrocytoma
Brain Tumor, Childhood
Central Nervous System Diseases
Central Nervous System Neoplasms
Brain Diseases
Ependymoma
Recurrence

Brain Neoplasms
Neuroectodermal Tumors
Brain Stem Glioma, Childhood
Craniopharyngioma
Neuroepithelioma
Oligodendroglioma
Meningioma
Glioma
Nervous System Neoplasms

Additional relevant MeSH terms:

Brain Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases

Central Nervous System Diseases
Central Nervous System Neoplasms
Brain Diseases
Nervous System Neoplasms

ClinicalTrials.gov processed this record on July 02, 2009