Clinical trial NCT02648633: Stereotactic Radiosurgery With Nivolumab and Valproate in Patients With Recurrent Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Glioblastoma
Keywords: Brain Cancer
Immunotherapy
Nivolumab
Radiosurgery
Gamma Knife
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2016-01-07
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Feasibility based on number of subjects who complete 4 doses of nivolumab
timeFrame: At 3 months following radiosurgery
measure: Incidence of adverse events
timeFrame: From the beginning of treatment until no sooner than 30 days following the last study treatment
Secondary outcomes:
measure: Clinical Response Rate
timeFrame: From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
Other outcomes:
measure: Incidence of Pseudoprogressions
timeFrame: From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Benjamin Purow, MD
role: PRINCIPAL_INVESTIGATOR
References: