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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 ottobre 2015 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

656

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: 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.
Altri nomi:
  • RAD001
Droga: 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.
Comparatore 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.
Droga: 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.
Droga: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Overall Survival (OS)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Progression Free Survival (PFS)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Novartis Pharmaceuticals

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 luglio 2009

Completamento primario (Effettivo)

1 gennaio 2014

Completamento dello studio (Effettivo)

1 gennaio 2014

Date di iscrizione allo studio

Primo inviato

8 aprile 2009

Primo inviato che soddisfa i criteri di controllo qualità

9 aprile 2009

Primo Inserito (Stima)

10 aprile 2009

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

3 novembre 2015

Ultimo aggiornamento inviato che soddisfa i criteri QC

8 ottobre 2015

Ultimo verificato

1 ottobre 2015

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

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

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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