Valproic Acid and Radiation Followed by Maintenance Valproic Acid and Bevacizumab in Children With High Grade Gliomas or Diffuse Intrinsic Pontine Glioma
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.
Glial Cell Tumors
Drug: Valproic acid
Radiation: Radiation therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Event free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]To determine the efficacy of combining valproic acid (VPA) with radiation, followed by maintenance VPA and bevacizumab in children with newly diagnosed high-grade gliomas and brainstem gliomas, as measured by EFS at one-year and two-years.
- To determine toxicities of VPA when combined with radiation and when combined with bevacizumab in the post-radiotherapy phase. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2009|
|Estimated Study Completion Date:||May 2019|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
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
All patients will receive bevacizumab (10mg/kg iv) during the maintenance phase every two weeks for a maximum duration of therapy of 24 months.
Other Name: AvastinRadiation: 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.
With the exception of patients with brainstem gliomas, 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 and radiation therapy.
Valproic Acid (VPA): 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: 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. During this time patients will receive standard radiation therapy.
Post Radiation Phase: Patients will continue to receive VPA as during radiation. If necessary, patients who had delays in radiation (e.g., secondary to schedule holidays or the need to have a new mask made) will complete their radiotherapy to the total prescribed protocol dose.
Maintenance Phase: Maintenance therapy will begin 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 by vein every two weeks, at the start of maintenance therapy. Maintenance therapy will continue uninterrupted if all laboratory tests continue to meet on-study criteria. In the absence of unacceptable toxicity or disease progression, patients will continue to receive protocol treatment for a maximum total duration of two years (including the radiation phase).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00879437
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center|
|Oklahoma City, Oklahoma, United States, 73126|
|United States, Texas|
|Driscoll Children's Hospital|
|Corpus Christi, Texas, United States, 78411|
|Children's Medical Center Dallas, Center for Cancer and Blood Disorders|
|Dallas, Texas, United States, 75235|
|Cook Children's Medical Center|
|Fort Worth, Texas, United States, 76104|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|