Stereotactic Radiosurgery With Nivolumab and Valproate in Patients With Recurrent Glioblastoma

NCT ID: NCT02648633

Last Updated: 2017-05-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-24
• Study Completion Date: 2017-02-21

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nivolumab & Valproate Following G.K.

Subjects will begin a valproate regimen prior to undergoing stereotactic radiosurgery (gamma knife) on a single lesion. Following the surgery, subjects will receive nivolumab every 2 weeks and daily valproate.

Group Type: EXPERIMENTAL

Stereotactic Radiosurgery

Intervention Type: RADIATION

Subjects will receive a single large dose of radiation to one or more lesions.

Nivolumab

Intervention Type: DRUG

3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.

Valproate

Intervention Type: DRUG

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.

Interventions

Stereotactic Radiosurgery

Subjects will receive a single large dose of radiation to one or more lesions.

Intervention Type: RADIATION

Nivolumab

3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Gamma Knife Radiosurgery; Opdivo; Valproic Acid; Sodium Valproate; Divalproex Sodium

Eligibility Criteria

Inclusion Criteria

• Confirmed malignant, recurrent glioblastoma or gliosarcoma
• Subject must have adequate organ function
• Subject must still be able to care for most of his or her personal needs

Exclusion Criteria

• Subject is pregnant
• Subject has extracranial metastatic or leptomeningeal disease
• Subject has an additional malignancy that is progressing or requires active treatment, exceptions being basal cell and squamous cell carcinomas of the skin, indolent prostate cancer, chronic lymphocytic leukemia, or in situ cervical cancer
• Subject has received chemotherapy, biological therapy, or had surgery 4 weeks prior to beginning the study
• Subject has had radiation therapy within 10 weeks prior to entering beginning the study
• Subject has had prior therapy with bevacizumab
• Subject has had previous treatment with carmustine wafer except when administered as first-line treatment no less than six months prior to beginning the study
• Subject requires escalating supraphysiologic doses of corticosteroids greater than 2 mg of dexamethasone or an equivalent
• Active autoimmune disease requiring systemic treatment within the past 3 months or any syndrome that requires immunosuppressive agents
• Interstitial lung disease or active, non-infectious pneumonitis
• Evidence of greater than Grade 1 CNS hemorrhage or greater than Grade 3 venous thromboembolism
• History of uncontrolled cardiac disease
• Subject unable or unwilling to have a head contrast enhanced MRI

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Benjamin Purow, MD

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Benjamin Purow, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

CA209-378

Identifier Type: OTHER

Identifier Source: secondary_id

18574

Identifier Type: -

Identifier Source: org_study_id