Vandetanib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Diffuse Brainstem Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Phase I Trial of Vandetanib (ZD6474, ZACTIMA) With Concurrent Radiation in Treatment of Newly Diagnosed Brainstem Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00472017
• Other study ID #: SJBG07-SJ
• Status: Completed
• Phase: Phase 1
• First received: May 8, 2007
• Last updated: October 11, 2012
• Start date: April 2007
• Est. completion date: October 2011

Study information

• Verified date: October 2012
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 21 Years

Eligibility

• Diagnosis of 1 of the following:

• Diffuse brainstem glioma

• High-grade glioma originating from brainstem

• Age must be greater than or equal to 2 years and less than 21 years

• Newly diagnosed disease

• 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• vandetanib
Oral vandetanib administration will start on the same day as RT. Treatment with vandetanib will extend for the entire duration of RT, and then will be continued after completion of RT for a maximum duration of 2 years.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To estimate the maximum tolerated dose (MTD) and to determine the dose-limiting toxicity (DLT) of vandetanib administered concurrently with radiation therapy (RT) in pediatric patients with newly diagnosed diffuse brainstem glioma.		3 Years	Yes
Secondary	To determine the toxicities associated with the chronic use of vandetanib in pediatric patients		3 Years	Yes
Secondary	To characterize the pharmacokinetics of vandetanib in pediatric patients		3 Years	No
Secondary	To evaluate the influence of specific polymorphisms on the pharmacokinetics of vandetanib in children		3 Years	No
Secondary	To prospectively investigate the role of innovative imaging techniques (e.g., perfusion/diffusion, susceptibility-weighted imaging, arterial spin labeling) in assessing the response to therapy, particularly in tumor vascularization and perfusion		3 Years	No
Secondary	To prospectively estimate the cumulative incidence of intratumoral hemorrhage in patients with diffuse brainstem glioma treated with vandetanib concurrently with and after RT in the context of a Phase I study		3 Years	No
Secondary	Prospectively assess the number of circulating endothelial cells and circulating endothelial progenitors before the start and during therapy and, if possible, to correlate these findings with tumor response, imaging studies, and other biological assays		3 Years	No

External Links

•   St. Jude Children's Research Hospital