Vandetanib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Diffuse Brainstem Glioma - Full Text View

Sponsors and Collaborators:	St. Jude Children's Research Hospital National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00472017

Purpose

RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving vandetanib together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vandetanib when given together with radiation therapy in treating young patients with newly diagnosed diffuse brain stem glioma .

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: vandetanib Procedure: 3-dimensional conformal radiation therapy Procedure: immunologic technique Procedure: laboratory biomarker analysis Procedure: pharmacological study Procedure: polymorphism analysis	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Vandetanib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase I Trial of Vandetanib (ZD6474, ZACTIMA) With Concurrent Radiation in Treatment of Newly Diagnosed Brainstem Glioma

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

Primary Outcome Measures:

Maximum tolerated dose [ Designated as safety issue: Yes ]
Dose-limiting toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Pharmacokinetics [ Designated as safety issue: No ]
Influence of polymorphisms on pharmacokinetics [ Designated as safety issue: No ]
Role of innovative imaging techniques in assessing response to therapy [ Designated as safety issue: No ]
Cumulative incidence of intratumoral hemorrhage [ Designated as safety issue: No ]
Correlation of number of circulating endothelial cells and circulating endothelial progenitors with tumor response, imaging studies, and other biological assays [ Designated as safety issue: No ]

Estimated Enrollment:	28
Study Start Date:	April 2007
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose and dose-limiting toxicity of vandetanib when administered with conformal radiotherapy in pediatric patients with newly diagnosed diffuse brainstem glioma.

Secondary

Determine the toxicity of chronic vandetanib in these patients.
Assess the pharmacokinetics of this drug in these patients.
Assess the influence of specific polymorphisms (e.g., CYP3A4/5) on the pharmacokinetics of this drug in these patients.
Determine, preliminarily, the role of innovative imaging techniques (e.g., perfusion/diffusion, susceptibility-weighted imaging, arterial spin labeling) in assessing the response to therapy (i.e., tumor vascularization and perfusion).
Assess the cumulative incidence of intratumoral hemorrhage in patients treated with vandetanib and radiotherapy.
Correlate the number of circulating endothelial cells and circulating endothelial progenitors with tumor response, imaging studies, and other biological assays.

OUTLINE: This is a dose-escalation study of vandetanib.

Patients undergo conformal radiotherapy once daily, 5 days a week, for 6 weeks. Patients also receive oral vandetanib once daily beginning on the same day as radiotherapy and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vandetanib until the maximum tolerated dose (MTD) is determined.

Blood samples are collected periodically for pharmacokinetic studies, polymorphism analysis (e.g., CYP3A4/5), and immunological laboratory methods (e.g., western blot assay). Imaging studies are also conducted periodically.

PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	2 Years to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Diffuse brainstem glioma
- High-grade glioma originating from brainstem
Newly diagnosed disease

PATIENT CHARACTERISTICS:

Lansky OR Karnofsky performance status 40-100%
ANC ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³ (transfusion independent)
Hemoglobin ≥ 8 g/dL (transfusion allowed)
Bilirubin < 1.5 times upper limit of normal (ULN) for age
ALT < 5 times ULN
Albumin ≥ 2 g/dL
Creatinine < 2 times ULN for age OR glomerular filtration rate > 70 mL/min
QTc interval < 450 msec by EKG
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Prior surgery allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00472017

Locations

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 901-495-4644

Sponsors and Collaborators

St. Jude Children's Research Hospital

National Cancer Institute (NCI)

Investigators

Study Chair:

Alberto Broniscer, MD

St. Jude Children's Research Hospital

More Information

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

Study ID Numbers:	CDR0000543871, SJCRH-SJBG07
Study First Received:	May 8, 2007
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00472017
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

untreated childhood brain stem glioma

Study placed in the following topic categories:

Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Glioma

Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type

Nervous System Diseases
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial

ClinicalTrials.gov processed this record on January 14, 2009