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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. oktober 2015 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

656

Fase

  • Fase 3

Kontakter og lokationer

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

Studiesteder

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

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:

  • 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

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: 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.
Medicin: 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.
Andre navne:
  • RAD001
Medicin: 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.
Placebo komparator: 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.
Medicin: 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.
Medicin: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Survival (OS)
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression Free Survival (PFS)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

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

Sponsor

Novartis Pharmaceuticals

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

1. juli 2009

Primær færdiggørelse (Faktiske)

1. januar 2014

Studieafslutning (Faktiske)

1. januar 2014

Datoer for studieregistrering

Først indsendt

8. april 2009

Først indsendt, der opfyldte QC-kriterier

9. april 2009

Først opslået (Skøn)

10. april 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

3. november 2015

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

8. oktober 2015

Sidst verificeret

1. oktober 2015

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

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 .

Kliniske forsøg med Avanceret mavekræft

Kliniske forsøg med Everolimus

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Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Madagascar

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner