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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00472017
First received: May 8, 2007
Last updated: October 11, 2012
Last verified: October 2012
  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
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Vandetanib (ZD6474, ZACTIMA) With Concurrent Radiation in Treatment of Newly Diagnosed Brainstem Glioma

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the toxicities associated with the chronic use of vandetanib in pediatric patients [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]
  • To characterize the pharmacokinetics of vandetanib in pediatric patients [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
  • To evaluate the influence of specific polymorphisms on the pharmacokinetics of vandetanib in children [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: April 2007
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pediatric Diffuse Brainstem Glioma Patients
Patients with newly diagnosed diffuse brainstem gliomas receive vandetanib.
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.
Other Names:
  • ZD6474
  • Zactima

Detailed 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.

  Eligibility

Ages Eligible for Study:   2 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00472017

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Alberto Broniscer, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00472017     History of Changes
Other Study ID Numbers: SJBG07-SJ
Study First Received: May 8, 2007
Last Updated: October 11, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
untreated childhood brain stem glioma

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on April 15, 2014