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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: vandetanib

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Alberto Broniscer, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: May 8, 2007
• First Submitted That Met QC Criteria: May 8, 2007
• First Posted (Estimate): May 10, 2007

Study Record Updates

• Last Update Posted (Estimate): October 15, 2012
• Last Update Submitted That Met QC Criteria: October 11, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: untreated childhood brain stem glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: SJBG07-SJ