Valproic Acid, Radiation, and Bevacizumab in Children With High Grade Gliomas or Diffuse Intrinsic Pontine Glioma

Summary

Currently, there are few effective treatments for the following aggressive brain tumors: glioblastoma multiforme, anaplastic astrocytoma, gliomatosis cerebri, gliosarcoma, or brainstem glioma. Surgery and radiation can generally slow down these aggressive brain tumors, but in the majority of patients, these tumors will start growing again in 6-12 months. Adding chemotherapy drugs to surgery and radiation does not clearly improve the cure rate of children with malignant gliomas.

The investigators are conducting this study to see if the combination of valproic acid and bevacizumab (also known as AvastinTM) with surgery and radiation will shrink these brain tumors more effectively and improve the chance of cure.

Conditions

• Glial Cell Tumors
• Malignant Gliomas
• Glioblastoma Multiforme
• Anaplastic Astrocytoma
• Gliomatosis Cerebri
• Gliosarcoma
• Brainstem Glioma
• Diffuse Intrinsic Pontine Glioma

Interventions

DRUG

Valproic acid

Daily (pre-XRT, During XRT, Post-XRT and Maintenance Therapy) Started at 15 mg/kg/day divided into three doses a day as soon as patients have recovered from surgery but no later than the first day of XRT. Dosage will be adjusted in increments of 5 mg/kg/day every 3-5 days to achieve and maintain trough concentrations between 85 and 115 mcg/ml

DRUG

Bevacizumab

All patients will receive bevacizumab (10 mg/kg iv) during the maintenance phase every two weeks for a maximum duration of therapy of 24 months.

RADIATION

Radiation therapy

Radiation therapy will start within 30 days of the definitive surgical procedure. Primary brain malignant gliomas will receive a total dose of between 54.0 and 59.4 Gy in 30-33 fractions over 6-7 weeks. Total dose will be 54.0 Gy for completely resected tumors and brainstem gliomas. The total dose will be 59.4 if the tumor is located in the brain but not the brainstem, and the tumor was incompletely resected. Primary spinal cord malignant gliomas will receive a total dose of between 50.4-54 Gy in 28-30 fractions over 5-6 weeks.

Sponsors & Collaborators

• Cook Children's Medical Center

  collaborator OTHER

• University of Oklahoma

  collaborator OTHER

• University of Texas, Southwestern Medical Center at Dallas

  collaborator OTHER

• The University of Texas Health Science Center at San Antonio

  collaborator OTHER

• M.D. Anderson Cancer Center

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Jack Su, MD · Baylor College of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Years

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-09-01

Primary Completion

2015-08-30

Completion

2017-10-02

FDA Drug

Yes

Countries

• United States

Study Locations