NCT02648633

Stereotactic Radiosurgery With Nivolumab and Valproate in Patients With Recurrent Glioblastoma

A Pilot Study to Evaluate the Feasibility of the Combined Use of Stereotactic Radiosurgery With Nivolumab and Concurrent Valproate in Patients With Recurrent Glioblastoma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: University of Virginia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the safety and feasibility of the immunotherapeutic agent nivolumab given in combination with gamma knife therapy and valproate in patients with recurrent glioblastoma, a common and lethal type of brain cancer.

Detailed description

Immune checkpoint inhibitors have the potential to treat a wide range of diverse cancers. Of particular interest to researchers is the PD-1 receptor-ligand interaction, a major pathway that many cancers hijack in order to suppress immune control. Anti-PD-1 antibodies such as nivolumab show a strong potential to treat many types of cancers including glioblastoma, the most common and most lethal brain cancer. This study will examine a means of further focusing immune response on glioblastoma by combining stereotactic "gamma knife" radiosurgery with nivolumab. The rationale behind this intervention is that the radiation therapy will enhance immune response rate by providing additional tumor antigens from dying cells. Additionally, a study from investigators at Johns Hopkins indicates that histone deacetylase (HDAC) inhibitors may boost the anti-cancer efficacy of PD-1 antibodies like nivolumab. Valproate, a class I HDAC inhibitor, will be used concurrently with nivolumab with the goal of enhancing the effects of both the nivolumab and the radiotherapy.

Conditions

• Glioblastoma

Interventions

Type	Name	Description
RADIATION	Stereotactic Radiosurgery	Subjects will receive a single large dose of radiation to one or more lesions.
DRUG	Nivolumab	3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.
DRUG	Valproate	Subjects will begin regimen of valproate prior to radiosurgery and continue to receive therapy concurrently with nivolumab. Subjects will receive valproate daily with a target serum level of 75-100 μg/ml.

Timeline

• Start date: 2016-05-24
• Primary completion: 2017-02-21
• Completion: 2017-02-21
• First posted: 2016-01-07
• Last updated: 2017-05-31

Locations

1 site across 1 country: United States