- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Virginia
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Charlottesville, Virginia, United States, 22908
- University of Virginia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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Subjects will receive a single large dose of radiation to one or more lesions.
Other Names:
3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.
Other Names:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility based on number of subjects who complete 4 doses of nivolumab
Time Frame: At 3 months following radiosurgery
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Feasibility of the radiosurgery and drug combination will be determined based on the number of subjects who complete at least 4 doses of nivolumab.
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At 3 months following radiosurgery
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Incidence of adverse events
Time Frame: From the beginning of treatment until no sooner than 30 days following the last study treatment
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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.
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From the beginning of treatment until no sooner than 30 days following the last study treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Response Rate
Time Frame: From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
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Response to therapy will be evaluated by means of RANO criteria.
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From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Pseudoprogressions
Time Frame: From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
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Pseudoprogression, the transient increase in apparent tumor size, will be documented.
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From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Benjamin Purow, MD, University of Virginia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Tranquilizing Agents
- Psychotropic Drugs
- GABA Agents
- Anticonvulsants
- Antimanic Agents
- Immune Checkpoint Inhibitors
- Nivolumab
- Valproic Acid
Other Study ID Numbers
- 18574
- CA209-378 (Other Identifier: University of Virginia)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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