GlioblastomaPhase 1NCT02648633
Stereotactic Radiosurgery With Nivolumab and Valproate in Patients With Recurrent Glioblastoma
A Phase 1 study testing Stereotactic Radiosurgery, Nivolumab and Valproate in people with Glioblastoma, run by University of Virginia at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Stereotactic Radiosurgery, Nivolumab and Valproate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 24 May 2016to 21 Feb 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22908
About this study
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
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.
Read the 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
- Being tested
- Stereotactic Radiosurgery, Nivolumab, Valproate
- Keywords
- Brain Cancer, Immunotherapy, Nivolumab, Radiosurgery, Gamma Knife
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic RadiosurgeryRadiation
Also called Gamma Knife Radiosurgery
Subjects will receive a single large dose of radiation to one or more lesions.
NivolumabDrug
Also called Opdivo
3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.
ValproateDrug
Also called Valproic Acid, Sodium Valproate, Divalproex Sodium
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Radiation: Stereotactic Radiosurgery; Drug: Nivolumab; Drug: Valproate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From the beginning of treatment until no sooner than 30 days following the last study treatment
Secondary outcomes (1)
Clinical Response Rate
Response to therapy will be evaluated by means of RANO criteria.
Measured: From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2016 (estimated)
- Study start24 May 2016
- Primary completion21 Feb 2017
- Study completion21 Feb 2017
Why it stopped: The pharmaceutical company (BMS) would no longer provide nivolumab for the study, so the study was terminated early.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Benjamin Purow, MD, University of Virginia
- Investigators
- Benjamin Purow, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02648633
- Sponsor's protocol ID
- 18574
- Other IDs
- CA209-378
- Status last verified
- May 2017
- First submitted
- 16 Dec 2015
- Last updated
- 31 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02648633
- Acronym / sponsor ID
- 18574
- Conditions
- Glioblastoma
- Keywords
- Brain Cancer, Immunotherapy, Nivolumab, Radiosurgery, Gamma Knife
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The pharmaceutical company (BMS) would no longer provide nivolumab for the study, so the study was terminated early.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 24 May 2016 (actual)
- Primary completion
- 21 Feb 2017 (actual)
- Study completion
- 21 Feb 2017 (actual)
- First posted
- 7 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab & Valproate Following G.K. | Experimental | Radiation: Stereotactic Radiosurgery, Drug: Nivolumab, Drug: ValproateSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic RadiosurgeryAlso: Gamma Knife RadiosurgerySubjects will receive a single large dose of radiation to one or more lesions. | Radiation | Nivolumab & Valproate Following G.K. |
| NivolumabAlso: Opdivo3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery. | Drug | Nivolumab & Valproate Following G.K. |
| ValproateAlso: Valproic Acid, Sodium Valproate, Divalproex SodiumSubjects 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. | Drug | Nivolumab & Valproate Following G.K. |
Primary outcome
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.
1 secondary outcome
Clinical Response Rate
Time frame: From the beginning of treatment until documented disease progression or date of death, assessed up to 48 months.
Results and safety
The study was stopped early (reason given: The pharmaceutical company (BMS) would no longer provide nivolumab for the study, so the study was terminated early.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Purow, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Stereotactic Radiosurgery, Nivolumab and Valproate in people with Glioblastoma, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The pharmaceutical company (BMS) would no longer provide nivolumab for the study, so the study was terminated early.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility based on number of subjects who complete 4 doses of nivolumab (time frame: At 3 months following radiosurgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2017.