NCT00879437

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

A Phase 2 Study of Valproic Acid and Radiation, Followed by Maintenance Valproic Acid and Bevacizumab in Children With Newly Diagnosed High-grade Gliomas or Brainstem Gliomas

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

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.

Detailed description

With the exception of patients with diffuse intrinsic pontine glioma (DIPG), all patients should have the maximal surgical resection that can be safely performed prior to study entry. Submission of frozen tumor is strongly encouraged. After recovery from neurosurgery, all patients will start valproic acid (VPA) and radiation therapy. VPA will be started at 15 mg/kg/day divided into three doses a day, ideally 48 hours prior to first day of radiation therapy, but no later than the first day of radiation therapy. Patients may also begin VPA sooner if they have post-operative seizures and require an anti-convulsant. Radiation phase (week 1-6): Radiation therapy should begin within 30 days of definitive surgery or radiographic diagnosis, whichever is the later date. Date of surgery or radiographic diagnosis is considered day 1, and radiation should start no later than day 31. VPA will be continued daily without interruption during radiation therapy. VPA doses will be adjusted in increments of 5 mg/kg/day every 3-5 days to achieve and maintain trough concentrations between 85 to 115 mcg/ml. All patients will receive standard radiation therapy which will last approximately six week. Post Radiation Phase (week 7-10): Patients will continue to receive VPA as previously dosed during radiation to maintain a trough concentration of 85-115 mcg/ml. Maintenance Phase (starting week 11): Maintenance therapy will begin approximately 4 weeks after completion of radiation or week 11, whichever comes first. Patients will continue VPA daily during maintenance therapy. All patients will start bevacizumab, 10 mg/kg intravenously every two weeks, at the start of maintenance therapy (week 11). Maintenance therapy will continue uninterrupted unless treatment related toxicities requires study drug interruption. In the absence of unacceptable toxicity or disease progression, patients will continue to receive protocol treatment for a maximum duration of two years (including the radiation phase).

Conditions

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

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2009-09-01
• Primary completion: 2015-08-30
• Completion: 2017-10-02
• First posted: 2009-04-10
• Last updated: 2021-07-21
• Results posted: 2021-07-21

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study