- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning 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
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 1
Kontakter och platser
Studieorter
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Virginia
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Charlottesville, Virginia, Förenta staterna, 22908
- University of Virginia
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: 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.
Andra namn:
3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.
Andra namn:
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.
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Feasibility based on number of subjects who complete 4 doses of nivolumab
Tidsram: 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
Tidsram: 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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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Clinical Response Rate
Tidsram: 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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Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Incidence of Pseudoprogressions
Tidsram: 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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Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Benjamin Purow, MD, University of Virginia
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Neoplasmer efter histologisk typ
- Neoplasmer
- Neoplasmer, körtel och epitel
- Astrocytom
- Gliom
- Neoplasmer, neuroepitelial
- Neuroektodermala tumörer
- Neoplasmer, könsceller och embryonala
- Neoplasmer, nervvävnad
- Glioblastom
- Läkemedels fysiologiska effekter
- Neurotransmittormedel
- Molekylära mekanismer för farmakologisk verkan
- Depressiva medel i centrala nervsystemet
- Enzyminhibitorer
- Antineoplastiska medel
- Antineoplastiska medel, immunologiska
- Lugnande medel
- Psykotropa droger
- GABA-agenter
- Antikonvulsiva medel
- Antimaniska medel
- Immune Checkpoint-hämmare
- Nivolumab
- Valproinsyra
Andra studie-ID-nummer
- 18574
- CA209-378 (Annan identifierare: University of Virginia)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
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