Stereotactic Radiosurgery With Nivolumab and Valproate in Patients With Recurrent Glioblastoma

NCT02648633 | Terminated Phase 1 DMC

• 2 other identifiers: 18574CA209-378
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma

Keywords

Brain Cancer; Immunotherapy; Nivolumab; Radiosurgery; Gamma Knife

Outcome Measures

Primary Outcomes (2)

• Feasibility based on number of subjects who complete 4 doses of nivolumab

  Feasibility of the radiosurgery and drug combination will be determined based on the number of subjects who complete at least 4 doses of nivolumab.

  At 3 months following radiosurgery

• Incidence of adverse events

  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.

  From the beginning of treatment until no sooner than 30 days following the last study treatment

Secondary Outcomes (1)

• Clinical Response Rate

  From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.

Other Outcomes (1)

• Incidence of Pseudoprogressions

  From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.

Study Arms (1)

Nivolumab & Valproate Following G.K.

EXPERIMENTAL

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; Drug: Nivolumab; Drug: Valproate

Interventions

Stereotactic Radiosurgery RADIATION

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

Also known as: Gamma Knife Radiosurgery

Nivolumab & Valproate Following G.K.

Nivolumab DRUG

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

Also known as: Opdivo

Nivolumab & Valproate Following G.K.

Valproate 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.

Also known as: Valproic Acid, Sodium Valproate, Divalproex Sodium

Nivolumab & Valproate Following G.K.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Radiosurgery; Nivolumab; Valproic Acid

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Benjamin Purow, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: January 7, 2016
• Study Start: May 24, 2016
• Primary Completion: February 21, 2017
• Study Completion: February 21, 2017
• Last Updated: May 31, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)