Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

Et forsøg til evaluering af flere regimer i nyligt diagnosticeret og tilbagevendende glioblastom (GBM AGILE)

29. oktober 2026 opdateret af: Global Coalition for Adaptive Research

GBM AGILE: Global Adaptive Trial Master Protocol: En international, sømløs fase II/III Response Adaptive Randomization Platform Trial designet til at evaluere flere regimer i nyligt diagnosticeret og tilbagevendende GBM

Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.

All institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (*).

Studieoversigt

Status

Status

Angiver den aktuelle rekrutteringsstatus eller den udvidede adgangsstatus.
Rekruttering

Betingelser

Betingelser

Den sygdom, lidelse, syndrom, sygdom eller skade, der undersøges. På ClinicalTrials.gov kan tilstande også omfatte andre sundhedsrelaterede problemer, såsom levetid, livskvalitet og sundhedsrisici.

Intervention / Behandling

Intervention / Behandling

En proces eller handling, der er i fokus for en klinisk undersøgelse. Interventioner omfatter lægemidler, medicinsk udstyr, procedurer, vacciner og andre produkter, der enten er til undersøgelse eller allerede er tilgængelige. Interventioner kan også omfatte ikke-invasive tilgange, såsom uddannelse eller ændring af kost og motion.

Detaljeret beskrivelse

Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM. Its goals are to identify effective therapies for glioblastoma and match effective therapies with patient subtypes. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to Arms based on their performance. The primary endpoint is overall survival (OS).

GBM AGILE is designed to efficiently evaluate therapies. The trial will be conducted under a single Master Investigational New Drug Application/Clinical Trial Application and Master Protocol, allowing multiple drugs and drug combinations from different pharmaceutical companies to be evaluated simultaneously. The plan is to add experimental therapies as new information about promising new drugs are identified and remove therapies as they complete their evaluation.

Undersøgelsestype

Undersøgelsestype

Beskriver karakteren af ​​en klinisk undersøgelse. Undersøgelsestyper omfatter interventionelle undersøgelser (også kaldet kliniske forsøg), observationsundersøgelser (herunder patientregistre) og udvidet adgang.
Interventionel

Tilmelding (Anslået)

Tilmelding

Antallet af deltagere i en klinisk undersøgelse. Den "forventede" tilmelding er det mål for antallet af deltagere, som forskerne skal bruge til undersøgelsen.
2250

Fase

Fase

Stadiet af et klinisk forsøg, der studerer et lægemiddel eller et biologisk produkt, baseret på definitioner udviklet af U.S. Food and Drug Administration (FDA). Fasen tager udgangspunkt i undersøgelsens formål, antallet af deltagere og andre karakteristika. Der er fem faser: Tidlig fase 1 (tidligere opført som fase 0), fase 1, fase 2, fase 3 og fase 4. Ikke relevant bruges til at beskrive forsøg uden FDA-definerede faser, herunder forsøg med enheder eller adfærdsmæssige indgreb.
  • Fase 2
  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiekontakt

Navn og kontaktoplysninger for den person, der kan besvare spørgsmål om tilmelding til en klinisk undersøgelse. Hvert sted, hvor undersøgelsen udføres, kan også have en specifik kontaktperson, som kan være bedre i stand til at besvare disse spørgsmål.

Undersøgelse Kontakt Backup

Studiesteder

  • Australien
    • New South Wales
      • St Leonards, New South Wales, Australien, 2065
        • Rekruttering
        • Northern Sydney Cancer Centre/Royal North Shore Hospital
        • Ledende efterforsker:
          • Helen Wheeler, MD
        • Kontakt:
      • Waratah, New South Wales, Australien, 2298
        • Aktiv, ikke rekrutterende
        • Calvary Mater Newcastle
    • Queensland
      • Herston, Queensland, Australien, 4029
        • Rekruttering
        • Royal Brisbane and Women's Hospital
        • Ledende efterforsker:
          • Zarnie Lwin, MD
        • Kontakt:
    • South Australia
      • Bedford Park, South Australia, Australien, 5042
    • Victoria
      • Heidelberg, Victoria, Australien, 3084
      • Melbourne, Victoria, Australien
        • Rekruttering
        • Peter MacCallum Cancer Centre
        • Ledende efterforsker:
          • Jim Whittle, MD
        • Kontakt:
        • Kontakt:
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
      • Toronto, Ontario, Canada, M5G 2C1
        • Rekruttering
        • Princess Margaret Cancer Centre
        • Ledende efterforsker:
          • Warren Mason, MD
        • Kontakt:
        • Kontakt:
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Aktiv, ikke rekrutterende
        • Montreal Neurological Institute and Hospital, McGill University
      • Sherbrooke, Quebec, Canada, J1H 5H3
        • Aktiv, ikke rekrutterende
        • Université de Sherbrooke
  • Forenede Stater
    • Alabama
      • Birmingham, Alabama, Forenede Stater, 35249
        • Rekruttering
        • University of Alabama at Birmingham
        • Ledende efterforsker:
          • Louis B Nabors, MD
        • Kontakt:
        • Kontakt:
    • California
      • La Jolla, California, Forenede Stater, 92093
      • Los Angeles, California, Forenede Stater, 90048
        • Aktiv, ikke rekrutterende
        • Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
      • Los Angeles, California, Forenede Stater, 90095
        • Aktiv, ikke rekrutterende
        • University of California, Los Angeles
      • Orange, California, Forenede Stater, 92868
        • Rekruttering
        • St. Joseph Hospital
        • Ledende efterforsker:
          • Lars Anker, MD
        • Kontakt:
      • San Francisco, California, Forenede Stater, 94143
        • Rekruttering
        • University of California, San Francisco
        • Ledende efterforsker:
          • Nicholas Butowski, MD
        • Kontakt:
      • Stanford, California, Forenede Stater, 94305
        • Afsluttet
        • Stanford Cancer Center
    • Colorado
      • Aurora, Colorado, Forenede Stater, 80045
        • Rekruttering
        • University of Colorado Denver
        • Ledende efterforsker:
          • Denise Damek, MD
        • Kontakt:
    • Connecticut
      • New Haven, Connecticut, Forenede Stater, 06511
        • Rekruttering
        • Yale Cancer Center / Smilow Cancer Hospital*
        • Ledende efterforsker:
          • Nicholas Blondin, MD
        • Kontakt:
    • Florida
      • Jacksonville, Florida, Forenede Stater, 32224
        • Afsluttet
        • Mayo Clinic Cancer Center
      • Miami, Florida, Forenede Stater, 33136
        • Rekruttering
        • Sylvester Comprehensive Cancer Center*
        • Ledende efterforsker:
          • Macarena I De La Fuente, MD
        • Kontakt:
      • Tampa, Florida, Forenede Stater, 33612
        • Rekruttering
        • Moffitt Cancer Center
        • Ledende efterforsker:
          • Patrick Grogan, MD
        • Kontakt:
        • Kontakt:
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30309
        • Aktiv, ikke rekrutterende
        • Piedmont Atlanta Hospital
      • Atlanta, Georgia, Forenede Stater, 30322
        • Aktiv, ikke rekrutterende
        • Winship Cancer Institute of Emory University
    • Louisiana
      • New Orleans, Louisiana, Forenede Stater, 70112
        • Afsluttet
        • LSU Health Sciences Center - New Orleans
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02114
        • Rekruttering
        • Massachusetts General Hospital
        • Ledende efterforsker:
          • Patrick Wen, MD
        • Kontakt:
          • Patrick Wen, MD
          • Telefonnummer: 617-726-5130
          • E-mail: pwen@mgb.org
      • Boston, Massachusetts, Forenede Stater, 02115
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48202
        • Afsluttet
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, Forenede Stater, 55407
        • Rekruttering
        • Allina Health Systems/Abbott Northwestern Hospital
        • Ledende efterforsker:
          • Andrea Wasilewski, MD
        • Kontakt:
      • Rochester, Minnesota, Forenede Stater, 55905
        • Afsluttet
        • Mayo Clinic Cancer Center - Rochester
    • Mississippi
      • Jackson, Mississippi, Forenede Stater, 39213
        • Afsluttet
        • University of Mississippi Medical Center
    • Missouri
      • St Louis, Missouri, Forenede Stater, 63110
        • Afsluttet
        • Washington University School of Medicine - Siteman Cancer Center
    • New York
      • New York, New York, Forenede Stater, 10032
        • Rekruttering
        • Columbia University Medical Center
        • Ledende efterforsker:
          • Andrew Lassman, MD
        • Kontakt:
      • New York, New York, Forenede Stater, 10016
        • Aktiv, ikke rekrutterende
        • Perlmutter Cancer Center, NYU Langone Health
      • New York, New York, Forenede Stater, 10029
        • Aktiv, ikke rekrutterende
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, Forenede Stater, 10065
        • Rekruttering
        • Memorial Sloan Kettering Cancer Center*
        • Ledende efterforsker:
          • Ingo Mellinghoff, MD
        • Kontakt:
        • Kontakt:
    • North Carolina
      • Durham, North Carolina, Forenede Stater, 27710
        • Aktiv, ikke rekrutterende
        • Duke University Medical Center
      • Winston-Salem, North Carolina, Forenede Stater, 272157
        • Rekruttering
        • Comprehensive Cancer Center of Wake Forest*
        • Ledende efterforsker:
          • Glenn Lesser, MD
        • Kontakt:
    • Ohio
      • Cleveland, Ohio, Forenede Stater, 44195
        • Rekruttering
        • Cleveland Clinic
        • Ledende efterforsker:
          • Mina Lobbous, MD
        • Kontakt:
        • Kontakt:
      • Cleveland, Ohio, Forenede Stater, 44106
      • Columbus, Ohio, Forenede Stater, 43210
        • Aktiv, ikke rekrutterende
        • Ohio State University Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104
        • Aktiv, ikke rekrutterende
        • University of Pennsylvania - Perelman Center for Advanced Medicine
      • Pittsburgh, Pennsylvania, Forenede Stater, 15232
        • Aktiv, ikke rekrutterende
        • University of Pittsburgh Medical Center - Hillman Cancer Center
      • Pittsburgh, Pennsylvania, Forenede Stater, 15212
        • Afsluttet
        • Allegheny General Hospital
    • South Carolina
      • Charleston, South Carolina, Forenede Stater, 29425
        • Rekruttering
        • Medical University of South Carolina - Hollings Cancer Center
        • Ledende efterforsker:
          • Scott Lindhorst, MD
        • Kontakt:
    • Texas
      • Austin, Texas, Forenede Stater, 78705
        • Aktiv, ikke rekrutterende
        • Texas Oncology - Austin
      • Dallas, Texas, Forenede Stater, 75390
        • Aktiv, ikke rekrutterende
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Forenede Stater, 77030
        • Aktiv, ikke rekrutterende
        • University of Texas - MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, Forenede Stater, 84112
        • Rekruttering
        • University of Utah - Huntsman Cancer Institute
        • Ledende efterforsker:
          • Howard Colman, MD, PhD
        • Kontakt:
        • Kontakt:
    • Virginia
      • Charlottesville, Virginia, Forenede Stater, 22908
        • Rekruttering
        • University of Virginia Health
        • Kontakt:
        • Ledende efterforsker:
          • David Schiff, MD
    • Washington
      • Seattle, Washington, Forenede Stater, 98101
        • Aktiv, ikke rekrutterende
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, Forenede Stater, 53226
        • Rekruttering
        • Froedtert Hospital/Medical College of Wisconsin
        • Ledende efterforsker:
          • Jennifer Connelly, MD
        • Kontakt:
        • Kontakt:
  • Frankrig
      • Bron, Frankrig, 69677
        • Rekruttering
        • Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
        • Ledende efterforsker:
          • Francois Ducray, MD
        • Kontakt:
      • Marseille, Frankrig, 13005
        • Rekruttering
        • Hopital de la Timone
        • Kontakt:
        • Ledende efterforsker:
          • Emelie Tabouret, MD
      • Paris, Frankrig, 75013
        • Rekruttering
        • Hopital Piti-Salpetriere
        • Kontakt:
        • Ledende efterforsker:
          • Mehdi Touat, MD
  • Schweiz
      • Zurich, Schweiz
        • Rekruttering
        • University Hospital Zurich
        • Ledende efterforsker:
          • Michael Weller, MD
        • Kontakt:
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Schweiz, 1011
        • Rekruttering
        • Centre Hospitalier Universitaire Vaudois Lausanne
        • Ledende efterforsker:
          • Andreas Hottinger, MD
        • Kontakt:
  • Tyskland
      • Cologne, Tyskland, 50937
        • Rekruttering
        • Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
        • Kontakt:
        • Ledende efterforsker:
          • Norbert Galldiks, Prof.
      • Frankfurt, Tyskland, 60528
        • Rekruttering
        • Dr. Senckenbergisches Institut für Neuroonkologie
        • Kontakt:
        • Ledende efterforsker:
          • Michael Ronellenfitsch, MD, PhD
      • Heidelberg, Tyskland, 69120
        • Rekruttering
        • Universitätsklinik Heidelberg
        • Ledende efterforsker:
          • Antje Wick, MD
        • Kontakt:
      • Mannheim, Tyskland, 68167
        • Rekruttering
        • Universitaetsklinikum Heidelberg - Neurologische Klinik
        • Ledende efterforsker:
          • Michael Platten, MD
        • Kontakt:
      • Regensburg, Tyskland, 93053
        • Rekruttering
        • Universitätsklinikum Regensburg
        • Ledende efterforsker:
          • Peter Hau, MD
        • Kontakt:
      • Tübingen, Tyskland, 72076
        • Rekruttering
        • Universitätsklinikum Tübingen
        • Ledende efterforsker:
          • Ghazaleh Tabatabai, MD
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Berettigelseskriterier

De nøglekrav, som personer, der ønsker at deltage i et klinisk studie, skal opfylde eller de egenskaber, de skal have. Kvalifikationskriterier består af både inklusionskriterier (som er nødvendige for at en person kan deltage i undersøgelsen) og eksklusionskriterier (som forhindrer en person i at deltage). Typer af berettigelseskriterier omfatter, om en undersøgelse accepterer raske frivillige, har alders- eller aldersgruppekrav eller er begrænset af køn.

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Newly Diagnosed Inclusion Criteria:

  • Age ≥ 18 years.
  • Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
  • Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
  • Availability of tumor tissue representative of GBM from definitive surgery or biopsy.

Recurrent Inclusion Criteria:

  • Age ≥ 18 years.
  • Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
  • Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
  • Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
  • Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
  • Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.

Newly Diagnosed Exclusion Criteria:

  • Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
  • Extensive leptomeningeal disease.
  • QTc > 470 msec
  • History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Recurrent Exclusion Criteria:

  • Early disease progression prior to 3 months (12 weeks) from the completion of RT.
  • More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)
  • Received any prior treatment with lomustine, agents part of any of the experimental arms, or bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
  • Any prior treatment with prolifeprospan 20 with carmustine wafer.
  • Any prior treatment with an intracerebral agent.
  • Receiving additional, concurrent, active therapy for GBM outside of the trial
  • Extensive leptomeningeal disease.
  • QTc > 470 msec
  • History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm

Deltagergruppe / Arm

En gruppe eller undergruppe af deltagere i et klinisk forsøg, der modtager en specifik intervention/behandling eller ingen intervention i henhold til forsøgets protokol.
Intervention / Behandling

Intervention / Behandling

En proces eller handling, der er i fokus for en klinisk undersøgelse. Interventioner omfatter lægemidler, medicinsk udstyr, procedurer, vacciner og andre produkter, der enten er til undersøgelse eller allerede er tilgængelige. Interventioner kan også omfatte ikke-invasive tilgange, såsom uddannelse eller ændring af kost og motion.
Aktiv komparator: Control Arm

Newly Diagnosed GBM: Radiation therapy (XRT) 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 2-6 weeks from the last day of radiation, and the start of the first cycle of Maintenance Therapy 2-6 weeks after the last day of radiotherapy. The start of all subsequent maintenance therapy cycles (2-12) every 4 weeks + 7 days after the first daily dose of temozolomide of the preceding cycle. Total number of cycles should comply with institutional or country standards. During maintenance therapy, the first cycle of temozolomide will be at 150 mg/m2 for Days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for Days 1-5 of a 28-day cycle.

Recurrent GBM: Lomustine started at 110 mg/m2/day on Day 1 of a 42-day cycle as per local standards. Treatment will continue for up to 6 total cycles.
Medicin: Temozolomide

Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg

Andre navne:
  • Temodar
  • Temodal
  • Temcad
Medicin: Lomustine

Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg

Andre navne:
  • CCNU
  • CeeNU
  • Gleostine
Stråling: Radiation

60 Gy
Eksperimentel: Regorafenib Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: Regorafenib (Dosage Form: Tablet for oral administration; Strength: 40 mg) 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).

Recurrent GBM: Regorafenib (Dosage Form: Tablet for oral administration; Strength: 40 mg) 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).
Medicin: Regorafenib

Dosage Form: Tablet for oral administration Strength: 40 mg Standard Regimen: 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off)

Andre navne:
  • BAY 73-4506
  • Stivarga
Eksperimentel: Paxalisib Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: Paxalisib (Dosage Form: Tablet for oral administration; Strength: 15 mg per tablet) 45 mg orally (PO) every day for 28 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 28 days for all subsequent cycles.

Recurrent GBM: Paxalisib (Dosage Form: Tablet for oral administration; Strength: 15 mg per tablet) 45 mg orally (PO) every day for 21 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 21 days for all subsequent cycles.
Medicin: Paxalisib

Dosage Form: Tablet for oral administration Strength: 15 mg Standard Regimen: 45 mg orally (PO) every day for 28 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 28 days for all subsequent cycles

Andre navne:
  • GDC-0084
Eksperimentel: VAL-083 Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: VAL-083 (Dosage Form: Infusion for intravenous administration; Strength: 30 mg/m2) on Day 1, 2 and 3 of 21-day cycle.

Recurrent GBM: VAL-083 (Dosage Form: Infusion for intravenous administration; Strength: 30 mg/m2) on Day 1, 2 and 3 of 21-day cycle.
Medicin: VAL-083

Dosage Form: Infusion for intravenous administration Strength: 40 mg per vial Standard Regimen: 30 mg/m2 on Day 1, 2 and 3 of 21-day cycle. The drug is available in powder form. It is reconstituted with 5 mL of 0.9% Sodium Chloride for Injection, USP. This will produce a solution of 40 mg VAL-083 in 5 mL. The required volume of reconstituted VAL-083 for the patient is then calculated at the rate of 30 mg/m2. The corresponding volume is further diluted into 250 mL of 0.9% Sodium Chloride for Injection, USP, prior to intravenous administration.

Andre navne:
  • Dianhydrogalactitol
Eksperimentel: VT1021 Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Rolling 6 design. Treatment as outlined in section "Experimental: VT1021 Treatment Arm" with the first 6 patients receiving VT1021 at 12 mg/kg twice weekly in combination with temozolomide and radiation therapy. If there are two dose limiting toxicities reported, the dose will be de-escalated to 9 mg/kg two times a week. 6 patients will then be receiving 9 mg/kg two times a week and observed for DLTs for 4 weeks.

Recurrent GBM: Dose Finding Phase is not applicable for patients with Recurrent GBM in the VT1021 treatment arm.
Medicin: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Eksperimentel: VT1021 Treatment Arm - Enhanced Safety Management (ESM)

Experimental: VT1021 Treatment Arm - Enhanced Safety Management (ESM) Newly diagnosed MGMT Methylated and Unmethylated GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. PK and PD assessments are done for patients as a part of ESM. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.

Recurrent GBM: ESM is not applicable for patients with Recurrent GBM in the VT1021 treatment arm.
Medicin: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Eksperimentel: VT1021 Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily and VT1021 (Dosage Form: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: As confirmed through the dose finding phase) twice weekly during radiation therapy. Rest period: 2-6 weeks from last day of radiation. VT1021 dosing will continue during the rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with VT1021. After 6 cycles, VT1021 only.

Recurrent GBM: VT1021 (Dosage Form: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: 12mg/kg) twice weekly.
Medicin: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Eksperimentel: Troriluzole Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Rolling 6 design. The first 6 patients will receive troriluzole at 100 mg BID for the first two weeks followed by 200 mg BID for the next two weeks in combination with temozolomide and radiation therapy. If there are two dose limiting toxicities (DLTs) reported, the dose will be de-escalated to 100 mg in the morning and followed by 200 mg in the evening. 6 patients will receive this dose and observed for 4 weeks. If there are two DLTs reported, then this dose will be de-escalated to 100 mg BID. 6 patients will then be receiving this dose and observed for DLTs for 4 weeks.

Recurrent GBM: Rolling 6 design. The first 6 patients receiving troriluzole 100 mg twice a day (BID) for the first two weeks followed by 200 mg BID for the next two weeks in combination with lomustine. The dose de-escalation is similar to that of newly diagnosed patients during the rolling 6 design.
Medicin: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andre navne:
  • BHV-4157
Eksperimentel: Troriluzole Treatment Arm - Enhanced Safety Management (ESM)

Newly diagnosed MGMT Methylated and Unmethylated GBM and Recurrent GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.
Medicin: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andre navne:
  • BHV-4157
Eksperimentel: Troriluzole Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily and troriluzole (Dosage Form: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. Rest period: 2-6 weeks from last day of radiation. Troriluzole dosing will continue during the rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with troriluzole. After 6 cycles, troriluzole only.

Recurrent GBM: Lomustine 100 mg/m2 orally on day 1 of a 42-day cycle in combination with troriluzole (Dosage Form: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. After 6 cycles, troriluzole only.
Medicin: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andre navne:
  • BHV-4157
Eksperimentel: ADI-PEG 20 Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Dose Finding Phase is not applicable for newly diagnosed patients on the ADI-PEG 20 treatment arm.

Recurrent GBM: Rolling 6 design. The first 6 patients will receive ADI-PEG 20 at 36 mg/m2 once a week in combination with lomustine 100 mg/m2 orally on day 1 of a 42-day cycle. 6 patients will receive this dose and be observed for 4 weeks. If there are two dose limiting toxicities (DLTs) reported, the dose will be de-escalated to 18 mg/m2 once a week. 6 patients will receive this dose and be observed for 4 weeks.
Biologisk: ADI-PEG 20

Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week

Andre navne:
  • Pegargiminase
Eksperimentel: ADI-PEG 20 Treatment Arm - Enhanced Safety Management (ESM)

Newly diagnosed MGMT Methylated and Unmethylated GBM: ESM is not applicable for newly diagnosed patients on the ADI-PEG 20 treatment arm.

Recurrent GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.
Biologisk: ADI-PEG 20

Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week

Andre navne:
  • Pegargiminase
Eksperimentel: ADI-PEG 20 Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy over 6 weeks. Temozolomide (75 mg/m2 orally daily and ADI-PEG 20 (Dosage Form: Solution for intramuscular injection; Strength: 11.5 ± 1.0 mg/ml; Dose: 36 mg/m2) once a week. Rest period: 2-6 weeks from last day of radiation. ADI-PEG 20 dosing will continue during rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Subsequent cycles will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with ADI-PEG 20. After 6 cycles, ADI-PEG 20 only for up to 104 weeks of total treatment.

Recurrent GBM: Lomustine 100 mg/m2 orally on day 1 of a 42-day cycle in combination with ADI-PEG 20 (Dosage Form: Solution for IM injection; Strength: 11.5 ± 1.0 mg/ml; Dose: As confirmed by dose finding phase, once a week. After 6 cycles, ADI-PEG 20 only for up to 104 weeks of total treatment.
Biologisk: ADI-PEG 20

Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week

Andre navne:
  • Pegargiminase
Eksperimentel: AZD1390 Treatment Arm

Newly Diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks in combination with AZD1390 given on days of radiation followed by 14 days with daily AZD1390. Rest Period 2-4 weeks from the last day of AZD1390. The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle, if there is no toxicity. Temozolomide will be administered for up to 6 cycles in the maintenance phase.
Medicin: AZD1390

Standard Regimen Newly Diagnosed: Given once daily on days of radiation and once daily for 14 consecutive days after completion of radiation.
Eksperimentel: Tinostamustine - Dose finding phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Tinostamustine Dosage Form: Infusion for intravenous administration; Rolling 6 design. Treatment as outlined in "Investigational: Tinostamustine Treatment Arm" with the first 6 patients receiving Tinostamustine at 80 mg/m2 over 60 minutes with two potential dose de-escalations. If there are two or more dose limiting toxicities at the tested dose, subsequent patients will be enrolled at the next lower dose level (60 mg/m2 and subsequently to 40 mg/m2).

Recurrent GBM: Rolling 6 design. Tinostamustine Dosage Form: Infusion for intravenous administration; Strength: Starting dose 80 mg/m2 on Day 1 of 21-day cycle for up to 12 cycles. The first 6 patients will receive Tinostamustine at 80 mg/m2 over 60 minutes with two potential dose de-escalations if there are two or more dose limiting toxicities at the tested dose, subsequent patients will be enrolled at the next lower dose level (60 mg/m2 and subsequently to 40 mg/m2).
Medicin: Tinostamustine

Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.

Andre navne:
  • EDO-S101
Eksperimentel: Tinostamustine - Enhanced Safety Management

Newly diagnosed MGMT Methylated and Unmethylated GBM: Treatment as outlined in "Investigational: Tinostamustine Treatment Arm". Dose as determined by the dose finding phase.

Recurrent GBM: Tinostamustine (Dosage Form: Infusion for intravenous administration; Strength: as determined though the dose finding phase on Day 1 of 21-day cycle for up to 12 cycles.
Medicin: Tinostamustine

Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.

Andre navne:
  • EDO-S101
Eksperimentel: Investigation arm: Tinostamustine

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT total of 60 Gy (2 Gy/fraction) over 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 2-6 weeks from the last day of radiation. Tinostamustine treatment period: Tinostamustine (Dosage Form: Infusion for intravenous administration; Strength: as determined though the dose finding phase) on Day 1 of 21-day cycle for up to 12 cycles.
Medicin: Tinostamustine

Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.

Andre navne:
  • EDO-S101

Hvad måler undersøgelsen?

Primære resultatmål

Primære resultatmål

I et klinisk studies protokol er det planlagte resultatmål, der er det vigtigste for at evaluere effekten af ​​en intervention/behandling. De fleste kliniske undersøgelser har ét primært resultatmål, men nogle har mere end ét.
Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Survival (OS)
Tidsramme: From date of randomization until the date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Overall survival is defined from the time of randomization to death from any cause. Patients still alive at the time of an analysis will be considered censored at their date of last contact.
From date of randomization until the date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Sekundære resultatmål

Sekundære resultatmål

I en klinisk undersøgelses protokol er et planlagt resultatmål, der ikke er lige så vigtigt som det primære resultatmål for at evaluere effekten af ​​en intervention, men som stadig er af interesse. De fleste kliniske undersøgelser har mere end ét sekundært resultatmål.
Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression-free survival (PFS)
Tidsramme: From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Progression-free survival is defined as the time from randomization to clinically determined progression or death from any cause. All participants will be included in the analysis of PFS.
From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Tumor Response
Tidsramme: From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Tumor response is categorized by Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). Response captured from initiation of study treatment until disease progression.
From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Duration of Response (CR + PR)
Tidsramme: From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Duration of response (CR+PR) is defined as time from date of response to date of clinically determined disease progression or death from any cause.
From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Sponsor

Den organisation eller person, der igangsætter undersøgelsen, og som har myndighed og kontrol over undersøgelsen.
Global Coalition for Adaptive Research

Samarbejdspartnere

Samarbejdspartnere

En anden organisation end sponsoren, der yder støtte til en klinisk undersøgelse. Denne støtte kan omfatte aktiviteter relateret til finansiering, design, implementering, dataanalyse eller rapportering.
Bayer
AstraZeneca
Kazia Therapeutics Limited
Biohaven Pharmaceuticals, Inc.
Kintara Therapeutics, Inc.
Vigeo Therapeutics, Inc.
Polaris Group
Knoa Pharma

Efterforskere

Efterforskere

En forsker involveret i et klinisk studie. Beslægtede termer omfatter stedets principal investigator, site sub-investigator, studieformand, undersøgelsesleder og undersøgelseshovedinvestigator.
  • Ledende efterforsker: Tim Cloughesy, MD, GCAR CMO and GBM AGILE Global PI

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

Studiestart

Den faktiske dato, hvor den første deltager blev tilmeldt en klinisk undersøgelse. Den "forventede" undersøgelses startdato er den dato, som forskerne tror vil være undersøgelsens startdato.
30. juli 2019

Primær færdiggørelse (Anslået)

Primær færdiggørelse

Den dato, hvor den sidste deltager i et klinisk studie blev undersøgt eller modtog en intervention for at indsamle endelige data for det primære resultatmål. Hvorvidt det kliniske studie sluttede i henhold til protokollen eller blev afsluttet, påvirker ikke denne dato. For kliniske undersøgelser med mere end ét primært resultatmål med forskellige afslutningsdatoer refererer dette udtryk til den dato, hvor dataindsamlingen er afsluttet for alle de primære resultatmål. Den "forventede" primære afslutningsdato er den dato, som forskerne tror vil være den primære afslutningsdato for undersøgelsen.
1. juni 2028

Studieafslutning (Anslået)

Studieafslutning

Den dato, hvor den sidste deltager i et klinisk studie blev undersøgt eller modtog en intervention/behandling for at indsamle endelige data for de primære resultatmål, sekundære udfaldsmål og uønskede hændelser (det vil sige den sidste deltagers sidste besøg). Den "forventede" undersøgelses afslutningsdato er den dato, som forskerne tror vil være undersøgelsens afslutningsdato.
1. juni 2030

Datoer for studieregistrering

Først indsendt

Først indsendt

Den dato, hvor undersøgelsens sponsor eller investigator første gang indsendte en undersøgelsespost til ClinicalTrials.gov. Der er typisk en forsinkelse på et par dage mellem den første indsendte dato og postens tilgængelighed på ClinicalTrials.gov (den første offentliggjorte dato).
23. maj 2019

Først indsendt, der opfyldte QC-kriterier

Først indsendt, der opfyldte QC-kriterier

Den dato, hvor undersøgelsens sponsor eller investigator første gang indsender en undersøgelsespost, der er i overensstemmelse med National Library of Medicine (NLM) kvalitetskontrol (QC) gennemgangskriterier. Sponsoren eller investigatoren skal muligvis revidere og indsende en undersøgelsespost en eller flere gange, før NLM's kvalitetskontrolkriterier er opfyldt. Det er sponsorens eller investigatorens ansvar at sikre, at undersøgelsesposten er i overensstemmelse med NLM QC-gennemgangskriterierne.
30. maj 2019

Først opslået (Faktiske)

Først opslået

Datoen, hvor undersøgelsesposten først var tilgængelig på ClinicalTrials.gov efter National Library of Medicine (NLM) kvalitetskontrol (QC) gennemgang er afsluttet. Der er typisk en forsinkelse på et par dage mellem den dato, hvor undersøgelsens sponsor eller investigator indsendte undersøgelsesposten, og den første offentliggjorte dato.
31. maj 2019

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

Sidste opdatering sendt

Den seneste dato, hvor ændringer i en undersøgelsespost blev gjort tilgængelig på ClinicalTrials.gov. Der kan være en forsinkelse mellem det tidspunkt, hvornår ændringerne blev indsendt til ClinicalTrials.gov af undersøgelsens sponsor eller investigator (datoen for sidste opdatering afsendt) og den sidste opdatering, der blev sendt.
2. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

Den seneste dato, hvor undersøgelsens sponsor eller investigator indsendte ændringer til en undersøgelsespost, der er i overensstemmelse med National Library of Medicine (NLM) kvalitetskontrol (QC) gennemgangskriterier. Det er sponsorens eller investigatorens ansvar at sikre, at undersøgelsesposten er i overensstemmelse med NLM QC-gennemgangskriterierne.
29. oktober 2026

Sidst verificeret

Sidst verificeret

Den seneste dato, hvor undersøgelsens sponsor eller investigator bekræftede oplysningerne om en klinisk undersøgelse på ClinicalTrials.gov som nøjagtige og aktuelle. Hvis en undersøgelse med rekrutteringsstatus som rekruttering; rekrutterer endnu ikke; eller aktiv, ikke rekruttering er ikke blevet bekræftet inden for de seneste 2 år, er undersøgelsens rekrutteringsstatus vist som ukendt.
1. juni 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

Andre undersøgelses-id-numre

Andre identifikatorer eller ID-numre end NCT-nummeret, der er tildelt til en klinisk undersøgelse af undersøgelsens sponsor, finansieringsgivere eller andre. Disse numre kan omfatte unikke identifikatorer fra andre forsøgsregistre og National Institutes of Health-bevillingsnumre.
  • GCAR-7213

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

UBESLUTET

IPD-planbeskrivelse

Global Coalition for Adaptive Research (GCAR) is in the planning stages at this time.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Cookieindstillinger

Vi bruger cookies for at sikre, at vi giver dig den bedste oplevelse på vores hjemmeside. For flere detaljer skal du læse omhyggeligt vores Politik om beskyttelse af personlige oplysninger og cookies. ...>>>Du kan når som helst ændre dine præferencer eller trække dit samtykke tilbage ved at slette cookies fra din hjemmeside eller computer som beskrevet i politikken. Accepter det og vælg dine præferencer ved at markere de tilsvarende felter i afsnittet "Administrer indstillinger" nedenfor. Læs vores servicevilkår omhyggeligt, inden du fortsætter med at bruge nogen del af dette websted.
«Administrer indstillinger