A Study of Avastin (Bevacizumab) and Irinotecan Versus Temozolomide Radiochemistry in Patients With Glioblastoma
20. oktober 2015 oppdatert av: Hoffmann-La Roche
This 2 arm study will compare the effect of Avastin + irinotecan versus temozolomide, in combination with conventional involved field radiotherapy, in patients with newly diagnosed glioblastoma and a non-methylated MGMT promoter.
Patients will be randomized 3:1 to receive Avastin 10mg/kg iv every 2 weeks + irinotecan 125mg/m2 iv every 2 weeks, or temozolomide 75mg/m2 po daily during radiotherapy followed by 6 cycles of temozolomide 150-200mg/m2 po daily on days 1-5 of each 4 week cycle.
The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
182
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Aachen, Tyskland, 52074
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Berlin, Tyskland, 13353
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Bochum, Tyskland, 44892
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Bonn, Tyskland, 53127
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Chemnitz, Tyskland, 09113
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Dresden, Tyskland, 01307
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Düsseldorf, Tyskland, 40225
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Erfurt, Tyskland, 99089
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Erlangen, Tyskland, 91054
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Frankfurt am Main, Tyskland, 60528
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Freiburg, Tyskland, 79106
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Göttingen, Tyskland, 37075
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Idar-Oberstein, Tyskland, 55743
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Kiel, Tyskland, 24105
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Köln, Tyskland, 50937
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Leipzig, Tyskland, 04103
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Mannheim, Tyskland, 68167
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Marburg, Tyskland, 35043
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Muenchen, Tyskland, 81377
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München, Tyskland, 81675
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Münster, Tyskland, 48149
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Regensburg, Tyskland, 93053
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Tübingen, Tyskland, 72076
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Ulm, Tyskland, 89081
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 70 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- adult patients, 18-70 years of age;
- glioblastoma, confirmed histologically;
- no previous chemotherapy or radiotherapy for glioblastoma;
- non-methylated MGMT promoter in the tumor.
Exclusion Criteria:
- prior systemic treatment for glioblastoma multiforme;
- prior treatment with Avastin;
- significant cardiovascular disease;
- other active malignant disease.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 1
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10mg/kg iv every 2 weeks
125mg/m2 iv every 2 weeks
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Aktiv komparator: 2
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75mg/m2 po daily during radiotherapy, followed by 150-200mg/m2/day po on days 1-5 of each 6x4 week cycle of adjuvant therapy
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months
Tidsramme: 6 months
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Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first.
Progression was defined as 25 percent (%) increase in size of enhancing tumor or any new tumor on gadolinium contrast agent magnetic resonance imaging (Gd-MRI) scans, or neurologically worse, and steroids stable or increased.
Percentage of participants achieving PFS without disease progression or death was reported.
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6 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Progression-Free Survival (PFS)
Tidsramme: From baseline to the end of the study (up to 4.5 years)
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Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first.
Progression was defined as 25% increase in size of enhancing tumor or any new tumor on Gd-MRI scans, or neurologically worse, and steroids stable or increased.
PFS was estimated using Kaplan-Meier method.
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From baseline to the end of the study (up to 4.5 years)
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Overall Survival (OS)
Tidsramme: From baseline until death (up to 4.5 years)
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Overall survival was defined as the time from randomization to death from any cause.
OS was estimated using Kaplan-Meier method.
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From baseline until death (up to 4.5 years)
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Percentage of Participants Who Discontinued
Tidsramme: From baseline until death (up to 4.5 years)
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Discontinuation was defined as the percentage of participants who permanently discontinued treatment in either treatment arm.
Percentage of participant with individual discontinuation reason are reported.
CNS: central nervous system; CTCAE: Common Terminology Criteria for Adverse Events .
Other reason refers to any other reason than the specified ones.
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From baseline until death (up to 4.5 years)
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Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
Tidsramme: 4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6
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BOR was defined as the best response observed for a participant during assessment.
Number of participants who had BOR as CR and number of participants who had BOR as CR or PR were reported.
Complete response was defined as disappearance of all enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, off steroids, and neurologically stable or improved.
Partial response was defined as 50% reduction in size of enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved.
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4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6
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Percentage of Participants With Response on FLAIR Imaging
Tidsramme: At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years)
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FLAIR lesions were determined as "stable", "progressive" or "decreased". FLAIR lesions was determined as "progressive" only if they were not be attributed to causes apart from tumor infiltration (sequelae of radiation therapy, demyelination, ischemia, infection, seizures, or other treatment effects). Percentage of participants are based on ITT population. Dis.=Discontinuation. |
At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years)
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Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Tidsramme: Baseline, Post-Baseline (up to Month 30)
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The EORTC QLQ-C30 incorporates: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale.
Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent').
Scores were averaged and transformed to 0-100 scale; higher score for Global Qol/functional scales=better level of functioning or a higher score for symptom scale=greater degree of symptoms.
The change in global health status was determined to be the difference in values at baseline and each specific visit.
The term ''baseline'' refers to the time of randomization to the maintenance phase.
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Baseline, Post-Baseline (up to Month 30)
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Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Tidsramme: Baseline, Post-Baseline (up to Month 30)
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EORTC QLQ-BN20 consisted of 20 items assessing visual disorders, motor dysfunction, communication deficit, various disease symptoms (e.g.
headaches and seizures), treatment toxicities (e.g.
hair loss) and future uncertainty.
All of the 20 items are rated on a 4 point Likert scale from 1=not at all, 2=a little, 3=quite a bit and 4=very much, and were linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
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Baseline, Post-Baseline (up to Month 30)
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Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
Tidsramme: Baseline, Post-Baseline (up to Month 30)
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The MMSE briefly measures orientation to time and place, immediate recall, short-term verbal memory, calculation, language and construct ability.
Each area tested had a designated point value, the total score can range from 0 to 30, with a higher score indicating better function.
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Baseline, Post-Baseline (up to Month 30)
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Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30)
Tidsramme: Baseline, Post-Baseline (up to Month 30)
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KPS is an 11-level score (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100) which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.
Deterioration in KPS was defined as decrease of 20 or more points in KPS score.
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Baseline, Post-Baseline (up to Month 30)
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Percentage of Participants Who Received Corticosteroid for Glioblastoma
Tidsramme: From baseline to Month 6
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Participants used corticosteroids for the glioblastoma condition.
Corticosteroids included dexamethasone, methylprednisone, fortecortin, hydrocortisone, urbason, and prednisolone.
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From baseline to Month 6
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Time to Treatment Failure
Tidsramme: From baseline until end of study (up to 4.5 years)
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From baseline until end of study (up to 4.5 years)
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- Schafer N, Proescholdt M, Steinbach JP, Weyerbrock A, Hau P, Grauer O, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Grau S, Hanel M, Schnell O, Krex D, Vajkoczy P, Tabatabai G, Mack F, Schaub C, Tzaridis T, Niessen M, Kebir S, Leutgeb B, Urbach H, Belka C, Stummer W, Glas M, Herrlinger U. Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma. Neuro Oncol. 2018 Jun 18;20(7):975-985. doi: 10.1093/neuonc/nox204.
- Herrlinger U, Schafer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hanel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tuttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. J Clin Oncol. 2016 May 10;34(14):1611-9. doi: 10.1200/JCO.2015.63.4691. Epub 2016 Mar 14.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. juni 2010
Primær fullføring (Faktiske)
1. september 2014
Studiet fullført (Faktiske)
1. september 2014
Datoer for studieregistrering
Først innsendt
16. juni 2009
Først innsendt som oppfylte QC-kriteriene
26. august 2009
Først lagt ut (Anslag)
27. august 2009
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
20. november 2015
Siste oppdatering sendt inn som oppfylte QC-kriteriene
20. oktober 2015
Sist bekreftet
1. oktober 2015
Mer informasjon
Begreper knyttet til denne studien
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
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Antineoplastiske midler
- Antineoplastiske midler, Alkylering
- Alkyleringsmidler
- Topoisomerasehemmere
- Antineoplastiske midler, immunologiske
- Angiogenese-hemmere
- Angiogenesemodulerende midler
- Vekststoffer
- Veksthemmere
- Topoisomerase I-hemmere
- Temozolomid
- Bevacizumab
- Irinotekan
Andre studie-ID-numre
- ML21965
- 2009-010390-21
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. .