Stereotactic Radiosurgery With Nivolumab and Valproate in Patients With Recurrent Glioblastoma
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|ClinicalTrials.gov Identifier: NCT02648633|
Recruitment Status : Terminated (The pharmaceutical company (BMS) would no longer provide nivolumab for the study, so the study was terminated early.)
First Posted : January 7, 2016
Last Update Posted : May 31, 2017
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma||Radiation: Stereotactic Radiosurgery Drug: Nivolumab Drug: Valproate||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study to Evaluate the Feasibility of the Combined Use of Stereotactic Radiosurgery With Nivolumab and Concurrent Valproate in Patients With Recurrent Glioblastoma|
|Actual Study Start Date :||May 24, 2016|
|Actual Primary Completion Date :||February 21, 2017|
|Actual Study Completion Date :||February 21, 2017|
Experimental: 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.
Radiation: Stereotactic Radiosurgery
Subjects will receive a single large dose of radiation to one or more lesions.
Other Name: Gamma Knife Radiosurgery
3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.
Other Name: Opdivo
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.
- Feasibility based on number of subjects who complete 4 doses of nivolumab [ Time Frame: At 3 months following radiosurgery ]Feasibility of the radiosurgery and drug combination will be determined based on the number of subjects who complete at least 4 doses of nivolumab.
- Incidence of adverse events [ Time Frame: From the beginning of treatment until no sooner than 30 days following the last study treatment ]Safety will be assessed by imaging of necrosis, incidence and severity of adverse events, changes in laboratory findings, physical examinations, vital signs, and the number of discontinuations due to adverse events.
- Clinical Response Rate [ Time Frame: From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months. ]Response to therapy will be evaluated by means of RANO criteria.
- Incidence of Pseudoprogressions [ Time Frame: From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months. ]Pseudoprogression, the transient increase in apparent tumor size, will be documented.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02648633
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Benjamin Purow, MD||University of Virginia|