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

15 août 2018 mis à jour par: 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

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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(either double only or double blind and open label) for reasons other than death, lost to follow-up or consent withdrawn entered long-term follow up

Type d'étude

Interventionnel

Inscription (Réel)

417

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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
Médicament: Sorafenib (Nexavar, BAY43-9006)
Sorafenib 400 mg will be administered orally, twice daily (approximately every 12 hours).
Comparateur placebo: Placebo
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Médicament: Placebo
Placebo (2 tablets) will be administered orally, twice daily (approximately every 12 hours).

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall Survival (OS)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Bayer

Collaborateurs

Amgen

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

15 octobre 2009

Achèvement primaire (Réel)

31 août 2012

Achèvement de l'étude (Réel)

30 août 2017

Dates d'inscription aux études

Première soumission

24 septembre 2009

Première soumission répondant aux critères de contrôle qualité

24 septembre 2009

Première publication (Estimation)

25 septembre 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

13 septembre 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

15 août 2018

Dernière vérification

1 août 2018

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 14295 (Autre identifiant: City of Hope Medical Center)
  • 2009-012007-25 (Numéro EudraCT)

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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