- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving 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
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
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Virginia
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Charlottesville, Virginia, Forente stater, 22908
- University of Virginia
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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.
Andre navn:
3 mg/kg of nivolumab will be administered through IV infusion every two weeks following stereotactic radiosurgery.
Andre navn:
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.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Feasibility based on number of subjects who complete 4 doses of nivolumab
Tidsramme: 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
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Clinical Response Rate
Tidsramme: 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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Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Incidence of Pseudoprogressions
Tidsramme: 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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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Benjamin Purow, MD, University of Virginia
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Neoplasmer etter histologisk type
- Neoplasmer
- Neoplasmer, kjertel og epitel
- Astrocytom
- Glioma
- Neoplasmer, Neuroepithelial
- Nevroektodermale svulster
- Neoplasmer, kjønnsceller og embryonale
- Neoplasmer, nervevev
- Glioblastom
- Fysiologiske effekter av legemidler
- Nevrotransmittere agenter
- Molekylære mekanismer for farmakologisk virkning
- Sentralnervesystemdepressiva
- Enzymhemmere
- Antineoplastiske midler
- Antineoplastiske midler, immunologiske
- Beroligende midler
- Psykotropiske stoffer
- GABA-agenter
- Antikonvulsiva
- Antimaniske midler
- Immune Checkpoint-hemmere
- Nivolumab
- Valproinsyre
Andre studie-ID-numre
- 18574
- CA209-378 (Annen identifikator: University of Virginia)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
Kliniske studier på Glioblastom
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Celldex TherapeuticsFullførtGlioblastom | Gliosarkom | Tilbakevendende glioblastom | Småcellet glioblastom | Kjempecelleglioblastom | Glioblastom med oligodendroglial komponent | Tilbakefallende glioblastomForente stater
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Northwestern UniversityNational Cancer Institute (NCI)RekrutteringGlioblastom | Astrocytom | Tilbakevendende glioblastom | MGMT-Umetylert glioblastom | Glioblastom, IDH-villtypeForente stater
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Istituto Oncologico Veneto IRCCSBayer S.p.ARekrutteringGlioblastom, IDH-villtype | MGMT-metylert glioblastomItalia
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Northwestern UniversityNational Cancer Institute (NCI); Moleculin Biotech, Inc.RekrutteringMGMT-Umetylert glioblastom | Glioblastom, IDH-villtypeForente stater
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Vastra Gotaland RegionKarolinska Institutet; Oslo University Hospital; Aarhus University Hospital; Sahlgrenska University Hospital, Sweden og andre samarbeidspartnereHar ikke rekruttert ennåGlioblastom, IDH-villtype | MGMT-metylert glioblastom
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Massachusetts General HospitalHar ikke rekruttert ennåGlioblastom tilbakevendende, EGFR vIII mutant | Nydiagnostisert glioblastom, EGFRvIII-mutant | Tilbakevendende glioblastom, EGFR vIII negativForente stater
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City of Hope Medical CenterNational Cancer Institute (NCI)RekrutteringTilbakevendende glioblastom | Ildfast glioblastomForente stater
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Northwestern UniversityAgenus Inc.; CarTheraRekrutteringGlioblastoma Multiforme | Gliosarkom | Nylig diagnostisert glioblastom | Glioblastom, isositrisk dehydrogenase (IDH)-villtypeForente stater
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Celldex TherapeuticsFullførtGlioblastom | Gliosarkom | Småcellet glioblastom | Kjempecelleglioblastom | Glioblastom med oligodendroglial komponentForente stater, Canada, Australia, Israel, Taiwan, Storbritannia, Belgia, Frankrike, Spania, Tyskland, Østerrike, Brasil, Colombia, Tsjekkia, Hellas, Ungarn, India, Italia, Mexico, Nederland, New Zealand, Peru, Sveits, Thailand
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National Cancer Institute (NCI)SuspendertTilbakevendende glioblastom, IDH-Wildtype | MGMT-metylert glioblastom | Tilbakevendende MGMT-metylert glioblastomForente stater
Kliniske studier på Stereotactic Radiosurgery
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CyberKnife Centers of San DiegoUkjent
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National Taiwan University HospitalRekrutteringSekundær ondartet neoplasma i ryggradenTaiwan
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CyberKnife Centers of San DiegoUkjentTilbakevendende prostatakreftForente stater
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Hamilton Health Sciences CorporationOntario Clinical Oncology Group (OCOG); Juravinski Cancer Centre FoundationUkjentMetastatisk malign neoplasma til voksen hjerneCanada
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University Hospital HeidelbergRekruttering
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Swedish Medical CenterAktiv, ikke rekrutterende
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Community Cancer Center, Normal, IllinoisUkjentProstatakreft | Prostata neoplasma | Kreft i prostataForente stater
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Yale UniversityAvsluttetMelanom | Sarkom | Nyrecellekarsinom | Brystkreft | Tykktarmskreft | Lungekreft | Hjernemetastaser | Mage-tarmkreftForente stater
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Community Cancer Center, Normal, IllinoisFullførtTumor, godartet, optisk nerveForente stater
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University of California, San FranciscoAvsluttet