Clinical Trial: Valproic Acid and Radiation Followed by Maintenance Valproic Acid and Bevacizumab in Children With High Grade Gliomas or Diffuse Intrinsic Pontine Glioma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief 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 Summary:

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 mai
Sponsor: Baylor College of Medicine

Current Primary Outcome:

  • Event free survival [ Time Frame: 24 months ]
    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 ]


Original Primary Outcome: Event free survival [ Time Frame: 24 months ]

Current Secondary Outcome:

Original Secondary Outcome:

  • Overall survival [ Time Frame: interval of time between diagnosis and death ]
  • Disease Response [ Time Frame: time to progress or 24 months post treatment ]


Information By: Baylor College of Medicine

Dates:
Date Received: April 9, 2009
Date Started: July 2009
Date Completion: May 2019
Last Updated: June 20, 2016
Last Verified: June 2016