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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: vandetanib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pediatric Diffuse Brainstem Glioma Patients<br>Patients with newly diagnosed diffuse brainstem gliomas receive vandetanib. | Drug: vandetanib<br>* 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.<br>* Other names: Zactima;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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untreated childhood brain stem glioma