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Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

15. august 2018 opdateret af: Bayer

A Double-Blind Randomized Phase III Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

Trial of sorafenib versus placebo in the treatment of locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Eligible subjects were randomized 1:1 to sorafenib 800 mg daily or matching placebo. Progression was assessed every 8 weeks by modified RECIST criteria. Subjects had the option to unblind study treatment after progression and to receive open label sorafenib regardless of initial treatment assignment. Following discontinuation of study treatment, subjects were followed for survival every 3 months in long-term follow-up. Subjects who terminated study treatment (either double only or double blind and open label) for reasons other than death, lost to follow-up or consent withdrawn entered long-term follow up

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

417

Fase

  • Fase 3

Kontakter og lokationer

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

Studiesteder

  • Belgien
      • Bruxelles - Brussel, Belgien, 1000
  • Bulgarien
      • Sofia, Bulgarien, 1527
  • Danmark
      • Odense C, Danmark, 5000
  • Den Russiske Føderation
      • Obninsk, Den Russiske Føderation, 249036
  • Det Forenede Kongerige
      • Cardiff, Det Forenede Kongerige, CF14 2TL
      • Glasgow, Det Forenede Kongerige, G12 0YN
      • Leeds, Det Forenede Kongerige, LS9 7TF
      • London, Det Forenede Kongerige, SE1 9RT
      • London, Det Forenede Kongerige, SM2 5PT
      • Manchester, Det Forenede Kongerige, M20 4BX
      • Newcastle Upon Tyne, Det Forenede Kongerige, NE7 7DN
      • Sutton, Det Forenede Kongerige, SM2 5PT
    • Aberdeenshire
      • Aberdeen, Aberdeenshire, Det Forenede Kongerige, AB25 2ZN
  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater, 90048
      • Stanford, California, Forenede Stater, 94305-5820
    • Connecticut
      • New Haven, Connecticut, Forenede Stater, 06520
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30322
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02118
    • Michigan
      • Ann Arbor, Michigan, Forenede Stater, 48109
    • Missouri
      • Saint Louis, Missouri, Forenede Stater, 63110
    • New Mexico
      • Albuquerque, New Mexico, Forenede Stater, 87106
    • New York
      • New York, New York, Forenede Stater, 10029
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104
      • Pittsburgh, Pennsylvania, Forenede Stater, 15213-1863
    • Texas
      • Houston, Texas, Forenede Stater, 77030
    • Washington
      • Seattle, Washington, Forenede Stater, 98109-1023
  • Frankrig
      • Angers, Frankrig, 49933
      • Bordeaux, Frankrig, 33076
      • Caen, Frankrig, 14076
      • LILLE cedex, Frankrig, 59037
      • Lyon, Frankrig, 69373
      • MARSEILLE cedex, Frankrig, 13273
      • Paris, Frankrig, 75651
      • Villejuif, Frankrig, 94805
  • Holland
      • Groningen, Holland, 9713 GZ
      • Leiden, Holland, 2333 ZA
  • Italien
    • Campania
      • Napoli, Campania, Italien, 80131
    • Liguria
      • Genova, Liguria, Italien, 16132
    • Lombardia
      • Milano, Lombardia, Italien, 20133
      • Milano, Lombardia, Italien, 20122
      • Milano, Lombardia, Italien, 20162
    • Sicilia
      • Catania, Sicilia, Italien, 95029
    • Toscana
      • Pisa, Toscana, Italien, 56124
      • Siena, Toscana, Italien, 53100
    • Umbria
      • Perugia, Umbria, Italien, 06126
  • Japan
    • Aichi
      • Nagoya, Aichi, Japan, 466-8560
      • Nagoya, Aichi, Japan, 464-8681
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
    • Tokyo
      • Koto-ku, Tokyo, Japan, 135-8550
  • Kina
      • Beijing, Kina, 100730
      • Beijing, Kina, 100021
      • Chengdu, Kina, 610041
      • Hangzhou, Kina, 310022
      • Shanghai, Kina, 200127
      • Shanghai, Kina, 200030
      • Tianjin, Kina, 300060
    • Guangdong
      • Guangzhou, Guangdong, Kina, 510060
  • Korea, Republikken
      • Daejeon, Korea, Republikken, 301-721
      • Seoul, Korea, Republikken, 137-701
      • Seoul, Korea, Republikken, 110-744
      • Seoul, Korea, Republikken, 120-752
      • Seoul, Korea, Republikken, 135-710
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, Korea, Republikken, 138-736
        • Asan Medical Center
  • Polen
      • Gliwice, Polen, 44-101
      • Poznan, Polen, 60-355
      • Warszawa, Polen, 02-781
      • Warszawa, Polen, 04-141
  • Saudi Arabien
      • Riyadh, Saudi Arabien, 11211
  • Spanien
      • Barcelona, Spanien, 08035
    • Madrid
      • Majadahonda, Madrid, Spanien, 28222
  • Sverige
      • Göteborg, Sverige, 413 45
      • Linköping, Sverige, 581 85
      • Lund, Sverige, 221 85
      • Stockholm, Sverige, 171 76
  • Tyskland
    • Bayern
      • Erlangen, Bayern, Tyskland, 91054
      • München, Bayern, Tyskland, 81377
      • Würzburg, Bayern, Tyskland, 97080
    • Nordrhein-Westfalen
      • Essen, Nordrhein-Westfalen, Tyskland, 45122
      • Köln, Nordrhein-Westfalen, Tyskland, 50924
    • Sachsen
      • Leipzig, Sachsen, Tyskland, 04103
  • Østrig
      • Wien, Østrig, 1090

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

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

Inclusion Criteria:

  • Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular and Hurthle cell)
  • Poorly differentiated and other thyroid variants (e.g. insular, tall cell, etc.) are eligible provided that the histology has no medullary differentiation nor anaplastic features
  • Progression within 14 months (RECIST [Response Evaluation Criteria in Solid Tumors] should be used as a basis for the assessment of disease progression)
  • RAI (radioactive iodine) refractory

Exclusion Criteria:

  • Histologic subtypes of thyroid cancer other than differentiated (i.e. like anaplastic and medullary carcinoma, lymphoma or sarcoma)
  • Prior anti-cancer treatment with tyrosine kinase inhibitors, monoclonal antibodies (licensed or investigational) that target VEGF (vascular endothelial growth factor) or VEGF Receptors or other targeted agents
  • Prior anti-cancer treatment for thyroid cancer with use of chemotherapy (low dose chemotherapy for radiosensitization is allowed) or Thalidomide or any of its derivatives

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: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Sorafenib (Nexavar, BAY43-9006)
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Medicin: Sorafenib (Nexavar, BAY43-9006)
Sorafenib 400 mg will be administered orally, twice daily (approximately every 12 hours).
Placebo komparator: Placebo
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Medicin: Placebo
Placebo (2 tablets) will be administered orally, twice daily (approximately every 12 hours).

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
Tidsramme: Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years
PFS=time from randomization to first observed disease progression (radiological according to central assessment or clinical due to bone irradiation, whichever is earlier), or death due to any cause, if death occurred before progression. Progression was assessed by RECIST criteria, version 1.0, modified for bone lesions. PFS for participants without disease progression or death at the time of analysis or unblinding were censored at the last date of tumor assessment before unblinding. Participants with no tumor evaluation after baseline were censored at Day 1. PD (Progression Disease)=At least a 20% increase in sum of longest diameters (LD) of measured lesions taking as reference the smallest sum LD on study since the treatment started or the appearance of 1 or more new lesions. New lesions also constituted PD. In exceptional circumstances, unequivocal progression of a nonmeasured lesion may have been accepted as evidence of disease progression in participants with measurable disease.
Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Survival (OS)
Tidsramme: From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years
Overall survival was defined as the time (days) from date of randomization to date of death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Since the median value could not be estimated due to censored data, the percentage of participants who died is presented.
From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years
Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
Tidsramme: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Time to progression was defined at the time (days) from randomization to progression (based on central assessment [radiological and clinical progression due to bone irradiation])
From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Disease Control Rate (DCR) Based on Central Assessment
Tidsramme: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Disease control rate was defined as the proportion of subjects whose best response was complete response (CR), partial response (PR), or stable disease (SD). Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, CR and PR were to be confirmed by another scan at least 4 weeks later; SD had to be documented at least 4 weeks after date of randomization. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum. SD = steady state of disease which is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Response Rate Based on Central Assessment
Tidsramme: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Response rate was defined as the proportion of subjects whose best response was CR or PR. Per RECIST, CR and PR was to be confirmed by another scan at least 4 weeks later. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.
From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Duration of Response (DOR) Based on Central Assessment
Tidsramme: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.
From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Maximum Percent Reduction in Target Lesion Size Based on Central Assessment
Tidsramme: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
The magnitude of change from baseline in target lesion size in evaluable participants with scans was determined.
From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State)
Tidsramme: A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)
Sorafenib AUC(0-12h),ss (area under the concentration time curve from time 0 to 12 hours at steady state) was estimated from the steady state plasma concentration.
A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)

Samarbejdspartnere og efterforskere

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

Sponsor

Bayer

Samarbejdspartnere

Amgen

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)

15. oktober 2009

Primær færdiggørelse (Faktiske)

31. august 2012

Studieafslutning (Faktiske)

30. august 2017

Datoer for studieregistrering

Først indsendt

24. september 2009

Først indsendt, der opfyldte QC-kriterier

24. september 2009

Først opslået (Skøn)

25. september 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

13. september 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. august 2018

Sidst verificeret

1. august 2018

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 14295 (Anden identifikator: City of Hope Medical Center)
  • 2009-012007-25 (EudraCT nummer)

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 .

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