Clinical trial NCT00472017: Vandetanib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Diffuse Brainstem Glioma
Official title: Phase I Trial of Vandetanib (ZD6474, ZACTIMA) With Concurrent Radiation in Treatment of Newly Diagnosed Brainstem Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Keywords: untreated childhood brain stem glioma
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2007-05-10
Enrollment: 35
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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 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

Primary outcomes:
measure: 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.
timeFrame: 3 Years
Secondary outcomes:
measure: To determine the toxicities associated with the chronic use of vandetanib in pediatric patients
timeFrame: 3 Years
measure: To characterize the pharmacokinetics of vandetanib in pediatric patients
timeFrame: 3 Years
measure: To evaluate the influence of specific polymorphisms on the pharmacokinetics of vandetanib in children
timeFrame: 3 Years
measure: 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
timeFrame: 3 Years
measure: 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
timeFrame: 3 Years
measure: 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
timeFrame: 3 Years
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Alberto Broniscer, MD
role: PRINCIPAL_INVESTIGATOR
References: