- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT05263466
Establishing Radiolabelled PSMA as a Target for Glioma Treatment
Dosimetry and Immunohistochemistry Study to Establish Radiolabelled PSMA as a Potential Target in Glioma Treatment
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
One potential avenue of high grade glioma treatment involves a 'theranostic' radiotherapeutic approach. This consists of two stages: firstly, a particular protein expressed specifically by the tumour is radiolabelled with a targeted radioligand emitting gamma radiation, enabling confirmation of the presence, concentration and distribution of this target protein (diagnostic stage). Following this, a similar ligand is this time attached to an alpha or beta-emitter, enabling targeted tumour destruction (therapeutic stage).
There is growing, but limited, evidence that prostate specific membrane antigen (PSMA) is strongly and specifically expressed in high grade glioma and may be a potential theranostic target [Wernicke 2011, Unterrainer 2017]. It has already been used extensively as a theranostic target in metastatic prostate cancer, demonstrating safety and efficacy in this condition [Abou et al 2020].
The clinical outcomes shown in prostate cancer, along with evidence of PSMA expression in high grade glioma, led the study team to convene an Incubator Day with a group of experts to explore the possibility of developing a PSMA-targeting theranostic agent in high grade glioma. Expertise included PSMA theranostics (Prof Lewington), neuro-oncology (Dr Brazil, Guy's and St Thomas' Hospital (GSTT)), neurosurgery (Prof Ashkan, King's College Hospital (KCH)), neuropathology (Prof Al-Sarraj, KCH), neuroradiology (Dr Booth, KCH) PSMA PET imaging (Prof Gary Cook and Prof Alexander Hammers GSTT/KCL), nuclear physics (Prof Paul Marsden GSTT/KCL), and PSMA radiopharmaceutical chemistry (Prof Blowers, KCL).
It was concluded that a PSMA-targeting theranostic agent has the potential to be a safe and effective treatment for high grade glioma. The regulatory pathway should be eased enormously by the precedent of use in prostate cancer, which would obviate the need for pre-clinical studies.
This approach was conditional upon two objectives:
- Perform a series of five [68Ga]PSMA PET scans for dosimetry analysis and assessment of the retention of the tracer in the tumour (Using GSTT/KCL PET/MRI) prior to biopsy, at the same time as the patient's routine brain tumour imaging series. At time of recurrence a further [68 Ga]PSMA PET-MRI scan may be performed in each patient (depending on whether or not recurrence occurs during the study period) to assess for change in the standardised uptake value (SUV).
- Performing immunohistochemical analysis on high grade glioma specimens (prospectively in patients enrolled in this study with additional retrospective samples), in order to replicate published evidence on the expression of PSMA in such tumours, and also to demonstrate in the prospective cohort, a correlation between imaging detection of [68 Ga]PSMA and histopathological detection in stereotactic brain tumour biopsy samples (Using KCH neuropathology facilities).
Studietyp
Inskrivning (Förväntat)
Fas
- Inte tillämpbar
Kontakter och platser
Studiekontakt
- Namn: Thomas C Booth, PhD
- Telefonnummer: 07977509937
- E-post: thomasbooth@nhs.net
Studieorter
-
-
-
London, Storbritannien
- King's College London
-
Kontakt:
- Professor Reza Razavi, PhD
- Telefonnummer: 0)207 8483224
- E-post: reza.razavi@kcl.ac.uk
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Individuals of 18 years or older
- Referred for surgery (resection or biopsy) of presumed high grade primary brain tumour (based on imaging features of aggression e.g. perfusion imaging, diffusion restriction etc.). As standard, all patients will have had a full body CT and other investigations to rule out metastatic disease (this has a very high negative predictive value).
- Written informed consent
Exclusion Criteria:
- Patient already enrolled in a drug trial
- Contra-indication for MRI contrast
- Contra-indication for radiotracer
- Inability to give consent
- Patient is pregnant or planning to become pregnant
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Diagnostisk
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Brain tumour patients
Patients will be those undergoing routine care of primary brain tumours.
Study group patients will undergo additional PET-MRI examination and biopsies in addition to the standard of care.
|
For the diagnostic imaging aspect included in this pilot study, [68Ga]PSMA-11 will be used.
This is a peptidomimetic agent with a covalently bound chelator (HBED-CC) that is FDA-approved in prostate cancer imaging.
We will use PET-MRI to visualise a) the concentration and b) the distribution of this tracer to establish a functional map of primary brain tumour activity
All patients included in our study will undergo stereotactic surgery for biopsy/resection of the tumour as part of the standard of care at KCH.
During this study we will not vary from the surgical standard of care for primary brain tumours and will only extend the surgery time due to additional stereotactic biopsies (an additional 3 biopsies increasing the time of the operation by ~30 minutes).
Professor Ashkan (KCH) has defined the additional surgical risk of performing these biopsies to be ~0%, since targeted biopsies will only be taken within the tumour just before resection.
The stereotactic biopsy may be targeted to areas of high [68Ga]PSMA SUV within the tumour as defined by the PET MRI scan.
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Correlation of the PET-MRI PSMA signal intensity (arbitrary units) and glioma protein concentration (g/L) in a 1 x 1 x 1 cm region of interest (R value)
Tidsram: 5 years
|
PET-MRI signal will be recorded from different regions of interest within a glioma where stereotactic surgical biopsies taken and protein concentration determined.
|
5 years
|
Samarbetspartners och utredare
Samarbetspartners
Utredare
- Huvudutredare: Thomas C Booth, PhD, King's College London
Publikationer och användbara länkar
Allmänna publikationer
- Louis DN, Wesseling P, Aldape K, Brat DJ, Capper D, Cree IA, Eberhart C, Figarella-Branger D, Fouladi M, Fuller GN, Giannini C, Haberler C, Hawkins C, Komori T, Kros JM, Ng HK, Orr BA, Park SH, Paulus W, Perry A, Pietsch T, Reifenberger G, Rosenblum M, Rous B, Sahm F, Sarkar C, Solomon DA, Tabori U, van den Bent MJ, von Deimling A, Weller M, White VA, Ellison DW. cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading. Brain Pathol. 2020 Jul;30(4):844-856. doi: 10.1111/bpa.12832. Epub 2020 Apr 19.
- Wernicke AG, Edgar MA, Lavi E, Liu H, Salerno P, Bander NH, Gutin PH. Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Arch Pathol Lab Med. 2011 Nov;135(11):1486-9. doi: 10.5858/arpa.2010-0740-OA.
- Unterrainer M, Niyazi M, Ruf V, Bartenstein P, Albert NL. The endothelial prostate-specific membrane antigen is highly expressed in gliosarcoma and visualized by [68Ga]-PSMA-11 PET: a theranostic outlook for brain tumor patients? Neuro Oncol. 2017 Nov 29;19(12):1698-1699. doi: 10.1093/neuonc/nox172. No abstract available.
- Abou D, Benabdallah N, Jiang W, Peng L, Zhang H, Villmer A, Longtine MS, Thorek DLJ. Prostate Cancer Theranostics - An Overview. Front Oncol. 2020 Jun 5;10:884. doi: 10.3389/fonc.2020.00884. eCollection 2020.
Studieavstämningsdatum
Studera stora datum
Studiestart (Förväntat)
Primärt slutförande (Förväntat)
Avslutad studie (Förväntat)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 306945
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Studerar en amerikansk FDA-reglerad produktprodukt
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Gliom, elakartad
-
Children's Hospital of PhiladelphiaBlue Earth Diagnostics, Inc; Dragon Master FoundationRekryteringGliom | Höggradig Gliom | Gliom, elakartad | Diffus gliom | Gliom intrakranielltFörenta staterna
-
Children's Hospital of PhiladelphiaBlue Earth Diagnostics; Dragon Master FoundationHar inte rekryterat ännuGliom | Låggradigt Gliom | Gliom, elakartad | Låggradigt gliom i hjärnan | Gliom intrakranielltFörenta staterna
-
City of Hope Medical CenterNational Cancer Institute (NCI); Food and Drug Administration (FDA)Aktiv, inte rekryterandeÅterkommande glioblastom | Återkommande malignt gliom | Refraktärt malignt gliom | Återkommande WHO Grad III Gliom | Återkommande WHO Grad II Gliom | Refraktär glioblastom | Refraktär WHO Grade II Gliom | Refraktär WHO Grad III GliomFörenta staterna
-
Beijing Tiantan HospitalDuke UniversityOkändGlioblastom | Höggradig Gliom | Gliom, elakartad | Gliom av hjärnstammenKina
-
University of California, San FranciscoBeiGene USA, Inc.; Pacific Pediatric Neuro-Oncology ConsortiumRekryteringGlioblastom | Malignt gliom | Återkommande glioblastom | Återkommande WHO Grad III Gliom | WHO Grad III Gliom | IDH2-genmutation | IDH1-genmutation | Låggradig gliom | Återkommande WHO Grad II Gliom | WHO Grad II GliomFörenta staterna
-
National Cancer Institute (NCI)RekryteringGliom | Höggradig Gliom | Malignt gliom | Gliomas | Låggradig gliomFörenta staterna
-
ChimerixAktiv, inte rekryterandeGlioblastom | Diffus mittlinjegliom | H3 K27M Gliom | Thalamisk gliom | Infratentoriellt gliom | Basal Ganglia GliomFörenta staterna
-
City of Hope Medical CenterNational Cancer Institute (NCI)Aktiv, inte rekryterandeGlioblastom | Malignt gliom | WHO Grad III Gliom | Återkommande Gliom | Eldfast GliomFörenta staterna
-
Hospital del Río HortegaAvslutadGliom | Glioblastom | Låggradigt Gliom | Gliom, elakartad | Högkvalitativ GliomSpanien
-
SanofiAvslutadGlioblastoma Multiforme | Maligna gliom | Blandade gliomFörenta staterna
Kliniska prövningar på PET-MRI
-
Cambridge University Hospitals NHS Foundation TrustRekryteringBröstcancerStorbritannien
-
Università Vita-Salute San RaffaeleIRCCS San Raffaele; Associazione Italiana per la Ricerca sul CancroHar inte rekryterat ännuBröstcancer Kvinna | Lobulärt bröstkarcinom | Luminal A Bröstcancer | PET/MRI | Axillär lymfadenopati
-
NYU Langone HealthDendreonAvslutadProstatacancerFörenta staterna
-
Maastricht University Medical CenterAvslutadOvariella neoplasmerNederländerna
-
Institut de cancérologie Strasbourg EuropeRekrytering
-
IRCCS San RaffaeleIBFM- Consiglio Nazionale delle RicercheRekryteringBröstcancer | Sentinel lymfkörtel | Bröstcancer i ett tidigt stadiumItalien
-
Gustave Roussy, Cancer Campus, Grand ParisOkänd
-
Washington University School of MedicineNational Cancer Institute (NCI)Avslutad