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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 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Faktisk)

656

Fas

  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • 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
  • Frankrike
      • Avignon Cedex, Frankrike, 84082
        • Novartis Investigative Site
      • Clermont Ferrand cedex 1, Frankrike, 63003
        • Novartis Investigative Site
      • Clichy, Frankrike, 92110
        • Novartis Investigative Site
      • Dijon, Frankrike, 21079
        • Novartis Investigative Site
      • Lyon Cedex 08, Frankrike, 69373
        • Novartis Investigative Site
      • Marseille cedex 05, Frankrike, 13385
        • Novartis Investigative Site
      • Montpellier Cedex 5, Frankrike, 34298
        • Novartis Investigative Site
      • Nice Cedex 2, Frankrike, 06189
        • Novartis Investigative Site
      • Paris, Frankrike, 75015
        • Novartis Investigative Site
      • Pessac Cedex, Frankrike, 33604
        • Novartis Investigative Site
      • Poitiers, Frankrike, 86000
        • Novartis Investigative Site
      • Reims, Frankrike, 51092
        • Novartis Investigative Site
      • Rennes Cedex, Frankrike, 35062
        • Novartis Investigative Site
      • Toulouse Cedex 4, Frankrike, 31054
        • Novartis Investigative Site
      • Villejuif Cedex, Frankrike, 94805
        • Novartis Investigative Site
  • Förenta staterna
    • Arkansas
      • Fayetteville, Arkansas, Förenta staterna, 72703
        • Highlands Oncology Group DeptofHighlandsOncologyGrp(2)
    • California
      • Redlands, California, Förenta staterna, 92374
        • Loma Linda Oncology Medical Group Loma Linda
    • Michigan
      • Detroit, Michigan, Förenta staterna, 48202-2689
        • Henry Ford Hospital Dept. of Henry Ford Hospital
    • Minnesota
      • Minneapolis, Minnesota, Förenta staterna, 55455
        • University of Minnesota Cancer Center
    • Texas
      • Dallas, Texas, Förenta staterna, 75390-8527
        • University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(4)
      • Fort Worth, Texas, Förenta staterna, 76104
        • The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
      • Houston, Texas, Förenta staterna, 77030-4009
        • University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
    • Washington
      • Seattle, Washington, Förenta staterna, 98109-1023
        • University of Washington Cancer Care Seattle Cancer Alliance
  • 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
  • Kanada
    • British Columbia
      • North Vancouver, British Columbia, Kanada, V7L 2L7
        • Novartis Investigative Site
      • Vancouver, British Columbia, Kanada, V5Z 4E6
        • Novartis Investigative Site
    • Ontario
      • Toronto, Ontario, Kanada, M4N 3M5
        • Novartis Investigative Site
      • Toronto, Ontario, Kanada, M5B 1W8
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Kanada, H3G 1A4
        • Novartis Investigative Site
      • Sherbrooke, Quebec, Kanada, J1H 5N4
        • 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, Republiken av
      • Seoul, Korea, Republiken av, 136-705
        • Novartis Investigative Site
      • Taegu, Korea, Republiken av, 700 - 721
        • Novartis Investigative Site
    • Jeollabuk-do
      • Jeonju-si, Jeollabuk-do, Korea, Republiken av, 561-712
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Korea, Republiken av, 05505
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republiken av, 06351
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republiken av, 110 744
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republiken av, 03722
        • Novartis Investigative Site
  • Mexiko
    • Distrito Federal
      • México, Distrito Federal, Mexiko, 14080
        • Novartis Investigative Site
    • Guanajuato
      • León, Guanajuato, Mexiko, 37000
        • Novartis Investigative Site
  • Nederländerna
      • Amsterdam, Nederländerna, 1105 AZ
        • Novartis Investigative Site
  • Nya Zeeland
      • Auckland, Nya Zeeland
        • Novartis Investigative Site
  • Peru
    • Lima
      • San Borja, Lima, Peru, 41
        • Novartis Investigative Site
      • San Isidro, Lima, Peru, 27
        • Novartis Investigative Site
  • Ryska Federationen
      • Moscow, Ryska Federationen, 115478
        • Novartis Investigative Site
      • St. Petersburg, Ryska Federationen, 197758
        • Novartis Investigative Site
  • Spanien
    • Catalunya
      • Barcelona, Catalunya, Spanien, 08035
        • Novartis Investigative Site
  • Storbritannien
      • East Yorkshire, Storbritannien, HU16 5JQ
        • Novartis Investigative Site
      • London, Storbritannien, SW3 6JJ
        • Novartis Investigative Site
      • London, Storbritannien, WC1E 6HX
        • Novartis Investigative Site
      • Manchester, Storbritannien, M20 4BX
        • Novartis Investigative Site
      • Wolverhampton, Storbritannien, WV10 0QP
        • Novartis Investigative Site
    • Middlesex
      • Northwood, Middlesex, Storbritannien, HA6 2RN
        • Novartis Investigative Site
    • Surrey
      • Sutton, Surrey, Storbritannien, SM2 5PT
        • 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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Läkemedel: 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.
Andra namn:
  • RAD001
Läkemedel: 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-jämförare: 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.
Läkemedel: 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.
Läkemedel: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Overall Survival (OS)
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Progression Free Survival (PFS)
Tidsram: 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
Tidsram: 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
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Novartis Pharmaceuticals

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 juli 2009

Primärt slutförande (Faktisk)

1 januari 2014

Avslutad studie (Faktisk)

1 januari 2014

Studieregistreringsdatum

Först inskickad

8 april 2009

Först inskickad som uppfyllde QC-kriterierna

9 april 2009

Första postat (Uppskatta)

10 april 2009

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

3 november 2015

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

8 oktober 2015

Senast verifierad

1 oktober 2015

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

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

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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