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Safety and Efficacy of RAD001 (Everolimus) Monotherapy Plus Best Supportive Care in Patients With Advanced Gastric Cancer (AGC) (GRANITE-1)

8 octobre 2015 mis à jour par: Novartis Pharmaceuticals

A Randomized, Double-blind, Multi-center Phase III Study Comparing Everolimus (RAD001) Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Patients With Advanced Gastric Cancer After Progression on 1 or 2 Prior Systemic Chemotherapy

This study is designed to assess the safety and efficacy of RAD001 monotherapy in patients with advanced gastric cancer which has progressed after one or two lines of prior chemotherapy.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

656

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
      • Berlin, Allemagne, 13353
        • Novartis Investigative Site
      • Bielefeld, Allemagne, 33604
        • Novartis Investigative Site
      • Frankfurt, Allemagne, 60488
        • Novartis Investigative Site
      • Mainz, Allemagne, 55131
        • Novartis Investigative Site
      • München, Allemagne, 81675
        • Novartis Investigative Site
      • Offenburg, Allemagne, 77652
        • Novartis Investigative Site
      • Trier, Allemagne, 54290
        • Novartis Investigative Site
    • Baden-Württemberg
      • Mannheim, Baden-Württemberg, Allemagne, 68305
        • Novartis Investigative Site
  • Argentine
      • Buenos Aires, Argentine, C1264AAA
        • Novartis Investigative Site
      • Cordoba, Argentine, X5000IUG
        • Novartis Investigative Site
    • Viedma
      • Rio Negro, Viedma, Argentine, 8500
        • Novartis Investigative Site
  • Australie
    • Australian Capital Territory
      • Canberra, Australian Capital Territory, Australie, 2605
        • Novartis Investigative Site
    • Queensland
      • Herston, Queensland, Australie, 4029
        • Novartis Investigative Site
    • South Australia
      • Kurralta Park, South Australia, Australie, 5037
        • Novartis Investigative Site
      • North Adelaide, South Australia, Australie, 5006
        • Novartis Investigative Site
    • Victoria
      • Box Hill, Victoria, Australie, 3128
        • Novartis Investigative Site
      • Clayton, Victoria, Australie, 3168
        • Novartis Investigative Site
      • Footscray, Victoria, Australie, 3011
        • Novartis Investigative Site
      • Heidelberg, Victoria, Australie, 3084
        • Novartis Investigative Site
      • Prahran, Victoria, Australie, 3181
        • Novartis Investigative Site
  • Belgique
      • Charleroi, Belgique, 6000
        • Novartis Investigative Site
      • Gent, Belgique, 9000
        • Novartis Investigative Site
      • Leuven, Belgique, 3000
        • Novartis Investigative Site
      • Liege, Belgique, 4000
        • Novartis Investigative Site
  • Canada
    • British Columbia
      • North Vancouver, British Columbia, Canada, V7L 2L7
        • Novartis Investigative Site
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Novartis Investigative Site
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M5B 1W8
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H3G 1A4
        • Novartis Investigative Site
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Novartis Investigative Site
  • Chine
      • Beijing, Chine, 100039
        • Novartis Investigative Site
      • Beijing, Chine, 100036
        • Novartis Investigative Site
      • Guangzhou, Chine, 510060
        • Novartis Investigative Site
      • Shanghai, Chine, 200032
        • Novartis Investigative Site
      • Shanghai, Chine, 200003
        • Novartis Investigative Site
      • Shanghai, Chine, 200025
        • Novartis Investigative Site
    • Guangdong
      • Guangzhou, Guangdong, Chine, 510515
        • Novartis Investigative Site
    • Hebei
      • Shijiazhuang, Hebei, Chine, 050011
        • Novartis Investigative Site
    • Heilongjiang
      • Harbin, Heilongjiang, Chine, 150081
        • Novartis Investigative Site
    • Jiangsu
      • Nanjing, Jiangsu, Chine, 210002
        • Novartis Investigative Site
      • Suzhou, Jiangsu, Chine, 215006
        • Novartis Investigative Site
    • Liaoning
      • Shenyang, Liaoning, Chine
        • Novartis Investigative Site
    • Sichuan
      • Chengdu, Sichuan, Chine, 610041
        • Novartis Investigative Site
    • Zhejiang
      • Hangzhou, Zhejiang, Chine, 310016
        • Novartis Investigative Site
  • Corée, République de
      • Seoul, Corée, République de, 136-705
        • Novartis Investigative Site
      • Taegu, Corée, République de, 700 - 721
        • Novartis Investigative Site
    • Jeollabuk-do
      • Jeonju-si, Jeollabuk-do, Corée, République de, 561-712
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Corée, République de, 05505
        • Novartis Investigative Site
      • Seoul, Korea, Corée, République de, 06351
        • Novartis Investigative Site
      • Seoul, Korea, Corée, République de, 110 744
        • Novartis Investigative Site
      • Seoul, Korea, Corée, République de, 03722
        • Novartis Investigative Site
  • Espagne
    • Catalunya
      • Barcelona, Catalunya, Espagne, 08035
        • Novartis Investigative Site
  • France
      • Avignon Cedex, France, 84082
        • Novartis Investigative Site
      • Clermont Ferrand cedex 1, France, 63003
        • Novartis Investigative Site
      • Clichy, France, 92110
        • Novartis Investigative Site
      • Dijon, France, 21079
        • Novartis Investigative Site
      • Lyon Cedex 08, France, 69373
        • Novartis Investigative Site
      • Marseille cedex 05, France, 13385
        • Novartis Investigative Site
      • Montpellier Cedex 5, France, 34298
        • Novartis Investigative Site
      • Nice Cedex 2, France, 06189
        • Novartis Investigative Site
      • Paris, France, 75015
        • Novartis Investigative Site
      • Pessac Cedex, France, 33604
        • Novartis Investigative Site
      • Poitiers, France, 86000
        • Novartis Investigative Site
      • Reims, France, 51092
        • Novartis Investigative Site
      • Rennes Cedex, France, 35062
        • Novartis Investigative Site
      • Toulouse Cedex 4, France, 31054
        • Novartis Investigative Site
      • Villejuif Cedex, France, 94805
        • Novartis Investigative Site
  • Fédération Russe
      • Moscow, Fédération Russe, 115478
        • Novartis Investigative Site
      • St. Petersburg, Fédération Russe, 197758
        • Novartis Investigative Site
  • Hong Kong
      • Hong Kong SAR, Hong Kong
        • Novartis Investigative Site
  • Israël
      • Jerusalem, Israël, 9112001
        • Novartis Investigative Site
      • Petach Tikva, Israël, 49100
        • Novartis Investigative Site
      • Ramat Gan, Israël, 5266202
        • Novartis Investigative Site
      • Rehovot, Israël, 76100
        • Novartis Investigative Site
  • Italie
      • Frattamaggiore, Italie, 80020
        • Novartis Investigative Site
    • FI
      • Firenze, FI, Italie, 50134
        • Novartis Investigative Site
    • MI
      • Rozzano, MI, Italie, 20089
        • Novartis Investigative Site
    • MO
      • Modena, MO, Italie, 41100
        • Novartis Investigative Site
    • PN
      • Aviano, PN, Italie, 33081
        • Novartis Investigative Site
  • Japon
    • Aichi
      • Nagoya, Aichi, Japon, 464-8681
        • Novartis Investigative Site
    • Chiba
      • Kashiwa, Chiba, Japon, 277-8577
        • Novartis Investigative Site
    • Ehime
      • Matsuyama, Ehime, Japon, 791-0280
        • Novartis Investigative Site
    • Fukuoka
      • Fukuoka-city, Fukuoka, Japon, 812-8582
        • Novartis Investigative Site
    • Hokkaido
      • Sapporo-city, Hokkaido, Japon, 060-8648
        • Novartis Investigative Site
    • Kanagawa
      • Sagamihara, Kanagawa, Japon, 252-0380
        • Novartis Investigative Site
    • Miyagi
      • Sendai-city, Miyagi, Japon, 980-8574
        • Novartis Investigative Site
    • Osaka
      • OsakaSayama, Osaka, Japon, 589-8511
        • Novartis Investigative Site
      • Takatsuki-city, Osaka, Japon, 569-8686
        • Novartis Investigative Site
    • Saitama
      • Kitaadachi-gun, Saitama, Japon, 362-0806
        • Novartis Investigative Site
    • Tochigi
      • Utsunomiya, Tochigi, Japon, 320-0834
        • Novartis Investigative Site
    • Tokyo
      • Chuo-ku, Tokyo, Japon, 104-0045
        • Novartis Investigative Site
      • Koto, Tokyo, Japon, 135-8550
        • Novartis Investigative Site
      • Mitaka-city, Tokyo, Japon, 181-8611
        • Novartis Investigative Site
  • Mexique
    • Distrito Federal
      • México, Distrito Federal, Mexique, 14080
        • Novartis Investigative Site
    • Guanajuato
      • León, Guanajuato, Mexique, 37000
        • Novartis Investigative Site
  • Nouvelle-Zélande
      • Auckland, Nouvelle-Zélande
        • Novartis Investigative Site
  • Pays-Bas
      • Amsterdam, Pays-Bas, 1105 AZ
        • Novartis Investigative Site
  • Pérou
    • Lima
      • San Borja, Lima, Pérou, 41
        • Novartis Investigative Site
      • San Isidro, Lima, Pérou, 27
        • Novartis Investigative Site
  • Royaume-Uni
      • East Yorkshire, Royaume-Uni, HU16 5JQ
        • Novartis Investigative Site
      • London, Royaume-Uni, SW3 6JJ
        • Novartis Investigative Site
      • London, Royaume-Uni, WC1E 6HX
        • Novartis Investigative Site
      • Manchester, Royaume-Uni, M20 4BX
        • Novartis Investigative Site
      • Wolverhampton, Royaume-Uni, WV10 0QP
        • Novartis Investigative Site
    • Middlesex
      • Northwood, Middlesex, Royaume-Uni, HA6 2RN
        • Novartis Investigative Site
    • Surrey
      • Sutton, Surrey, Royaume-Uni, SM2 5PT
        • Novartis Investigative Site
  • Taïwan
      • Liouying Township, Taïwan
        • Novartis Investigative Site
      • Niaosong Township, Taïwan, 83301
        • Novartis Investigative Site
      • Taipei, Taïwan, 10048
        • Novartis Investigative Site
      • Taipei, Taïwan
        • Novartis Investigative Site
    • Taoyuan/ Taiwan ROC
      • Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taïwan, 33305
        • Novartis Investigative Site
  • Thaïlande
      • Bangkok, Thaïlande, 10700
        • Novartis Investigative Site
      • Bangkok, Thaïlande, 10400
        • Novartis Investigative Site
      • Songkla, Thaïlande, 90110
        • Novartis Investigative Site
  • États-Unis
    • Arkansas
      • Fayetteville, Arkansas, États-Unis, 72703
        • Highlands Oncology Group DeptofHighlandsOncologyGrp(2)
    • California
      • Redlands, California, États-Unis, 92374
        • Loma Linda Oncology Medical Group Loma Linda
    • Michigan
      • Detroit, Michigan, États-Unis, 48202-2689
        • Henry Ford Hospital Dept. of Henry Ford Hospital
    • Minnesota
      • Minneapolis, Minnesota, États-Unis, 55455
        • University of Minnesota Cancer Center
    • Texas
      • Dallas, Texas, États-Unis, 75390-8527
        • University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(4)
      • Fort Worth, Texas, États-Unis, 76104
        • The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
      • Houston, Texas, États-Unis, 77030-4009
        • University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
    • Washington
      • Seattle, Washington, États-Unis, 98109-1023
        • University of Washington Cancer Care Seattle Cancer Alliance

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:

  • Male or female patients > 18 years old
  • Histologically or cytologically confirmed and documented gastric adenocarcinoma
  • Documented progression after 1 or 2 prior chemotherapy treatments for advanced disease
  • ECOG Performance Status of < 2
  • Lab parameters within specifically defined intervals
  • Able to provide written informed consent

Exclusion Criteria:

  • Patients who have received > 2 prior systemic therapies for advanced disease
  • Administration of another anticancer therapy within 3 weeks prior to randomization
  • Chronic treatment with steroids or another immunosuppressive agent
  • Major surgery within 2 weeks prior to randomization
  • Patients with CNS metastases
  • Any other severe and/or uncontrolled medical condition

Other protocol-defined inclusion/exclusion criteria may apply

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: Everolimus + BSC
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
Médicament: Everolimus
Everolimus was formulated as tablets of 5 mg strength. In both treatment arms, the study drug was given by continuous oral daily dosing of 10 mg (2 tablets x 5 mg) each morning.
Autres noms:
  • RAD001
Médicament: Best Supportive Care (BSC)
Best supportive care is defined as care in accordance with the local practice of an individual institution or center, specifically excluding anti-cancer treatments.
Comparateur placebo: Placebo + BSC
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
Médicament: Best Supportive Care (BSC)
Best supportive care is defined as care in accordance with the local practice of an individual institution or center, specifically excluding anti-cancer treatments.
Médicament: Everolimus placebo
Placebo was formulated to be indistinguishable from the everolimus tablets, also formulated as tablets of 5 mg strength. In both treatment arms, the study drug was given by continuous oral daily dosing of 10 mg (2 tablets x 5 mg) each morning.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Overall Survival (OS)
Délai: 2.5 years
The primary objective of this study was to compare OS between everolimus + best supportive care (BSC) and placebo + BSC. OS, was defined as the time from date of randomization to the date of death due to any cause. If at the analysis cut-off date a patient was not known to have died, survival was censored at the date of the last contact. OS was analyzed using the Kaplan Meier estimates method.
2.5 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Progression Free Survival (PFS)
Délai: 2.5 years
Progression free survival was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, where progression was based on Investigator assessment of baseline and post-baseline scans according to RECIST. Progression free survival was censored if no PFS event was observed before the first to occur out of (i) the cut-off date, or (ii) the date when a further anticancer therapy was started. The censoring date was the date of the last adequate tumor assessment before either of these two events occurred. If a PFS event was observed after two or more missing or non-evaluable tumor assessments, then the date of progression was censored at the date of the last adequate tumor assessment; for a PFS event observed after a single missing or non-evaluable tumor assessment, the actual date of disease progression was used. Anslsis was done using Kaplan-Meier estimates method.
2.5 years
Patient Reported Outcome (PRO): Time to Definitive Deterioration of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Scores
Délai: 2.5 years
The EORTC QLQ-C30 global health status/quality of life sub-scale (QL) was pre-specified as the primary domain of interest, followed by physical functioning (PF), social functioning (SF) and emotional functioning (EF).The EORTC QLQ-C30 questionnaire, along with a module specific for gastric cancer patients (EORTC QLQ-STO22), was used to evaluate PRO. The QLQ-C30 has five function scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and a global health status/quality of life scale. In addition, there are questions that assess specific symptoms. The QLQ-STO22 consists of 22 questions that make up five multi-item scales (dysphagia, pain, reflux, eating and anxiety) and four single-item scales (dry mouth, tasting, body image and hair loss).
2.5 years
Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
Délai: 2.5 years
The ECOG PS scale was used to classify patients according to their functional impairment, with scores ranging from 0 (fully active) to 5 (dead). An analysis of the time to definitive deterioration of the ECOG PS by one category of the score from baseline was performed. Definitive deterioration was defined as a definitive increase by one category from baseline in ECOG PS, with no later improvements observed during the course of the study. A single measure reporting an increase in ECOG PS is sufficient to consider it as a definitive worsening only if it was the last one available for the patient. Kaplan-Meier method was used to estimate the distribution function of time to definitive worsening.
2.5 years
Overall Response Rate (ORR)
Délai: 2.5 years
ORR was defined as the proportion of patients with measurable disease in whom best overall response (OR) was either complete response (CR) or partial response (PR) according to RECIST criteria.
2.5 years
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax at Week 5
Délai: Week 5
Cmin is the minimum (trough) steady-state drug concentration in the blood during multiple dosing and Cmax is the maximum (peak) blood drug concentration after dose administration. Cmax is estimated as the maximum of C1h and C2H. C1h is 1 hour post-dose blood concentration and C2h is 2 hour post-dose blood concentration. Only valid pre-dose (Cmin), C1h, and C2h everolimus samples were included in the analysis. Valid pre-dose samples were confirmed blood samples collected at steady-state, collected immediately prior to dosing on the same study day, and collected at approximately 24 ± 4 hours after the previous dose and with no vomiting within the first 4 hours following the last dose. Valid C1h and C2h samples were confirmed blood samples collected at steady-state and within ± 1 hour window and with no vomiting within the first 4 hours following the current and previous dose.
Week 5
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax by Region Asia vs. Rest of the World (ROW) at Week 5
Délai: Week 5
Cmin is the minimum (trough) steady-state drug concentration in the blood during multiple dosing and Cmax is the maximum (peak) blood drug concentration after dose administration. Cmax is estimated as the maximum of C1h and C2H. C1h is 1 hour post-dose blood concentration and C2h is 2 hour post-dose blood concentration. Only valid pre-dose (Cmin), C1h, and C2h everolimus samples were included in the analysis. Valid pre-dose samples were confirmed blood samples collected at steady-state, collected immediately prior to dosing on the same study day, and collected at approximately 24 ± 4 hours after the previous dose and with no vomiting within the first 4 hours following the last dose. Valid C1h and C2h samples were confirmed blood samples collected at steady-state and within ± 1 hour window and with no vomiting within the first 4 hours following the current and previous dose.
Week 5

Collaborateurs et enquêteurs

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

Parrainer

Novartis Pharmaceuticals

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

1 juillet 2009

Achèvement primaire (Réel)

1 janvier 2014

Achèvement de l'étude (Réel)

1 janvier 2014

Dates d'inscription aux études

Première soumission

8 avril 2009

Première soumission répondant aux critères de contrôle qualité

9 avril 2009

Première publication (Estimation)

10 avril 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

3 novembre 2015

Dernière mise à jour soumise répondant aux critères de contrôle qualité

8 octobre 2015

Dernière vérification

1 octobre 2015

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CRAD001R2301
  • 2008-006544-20 (Numéro EudraCT)

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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