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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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.

Detailed Summary:

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.


Sponsor: St. Jude Children's Research Hospital

Current Primary Outcome: 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. [ Time Frame: 3 Years ]

Original Primary Outcome:

  • Maximum tolerated dose
  • Dose-limiting toxicity


Current Secondary Outcome:

  • To determine the toxicities associated with the chronic use of vandetanib in pediatric patients [ Time Frame: 3 Years ]
  • To characterize the pharmacokinetics of vandetanib in pediatric patients [ Time Frame: 3 Years ]
  • To evaluate the influence of specific polymorphisms on the pharmacokinetics of vandetanib in children [ Time Frame: 3 Years ]
  • 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 [ Time Frame: 3 Years ]
  • 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 [ Time Frame: 3 Years ]
  • 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 [ Time Frame: 3 Years ]


Original Secondary Outcome:

  • Toxicity
  • Pharmacokinetics
  • Influence of polymorphisms on pharmacokinetics
  • Role of innovative imaging techniques
  • Cumulative incidence of intratumoral hemorrhage
  • Correlation of number of circulating endothelial cells and circulating endothelial progenitors with tumor response, imaging studies, and other biological assays


Information By: St. Jude Children's Research Hospital

Dates:
Date Received: May 8, 2007
Date Started: April 2007
Date Completion:
Last Updated: October 11, 2012
Last Verified: October 2012