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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. října 2015 aktualizováno: 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.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

656

Fáze

  • Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Čtyřnásobek

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Lék: 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.
Ostatní jména:
  • RAD001
Lék: 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.
Komparátor placeba: 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.
Lék: 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.
Lék: 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.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Overall Survival (OS)
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Progression Free Survival (PFS)
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Novartis Pharmaceuticals

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. července 2009

Primární dokončení (Aktuální)

1. ledna 2014

Dokončení studie (Aktuální)

1. ledna 2014

Termíny zápisu do studia

První předloženo

8. dubna 2009

První předloženo, které splnilo kritéria kontroly kvality

9. dubna 2009

První zveřejněno (Odhad)

10. dubna 2009

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

3. listopadu 2015

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

8. října 2015

Naposledy ověřeno

1. října 2015

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

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

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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Podmínky

Vzácné nemoci

Drogové intervence

Doplňky stravy

Sponzor / Spolupracovníci

Místa

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