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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 de outubro de 2015 atualizado por: 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.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

656

Estágio

  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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.
Medicamento: 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.
Outros nomes:
  • RAD001
Medicamento: 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.
Comparador de 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.
Medicamento: 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.
Medicamento: 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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Overall Survival (OS)
Prazo: 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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Progression Free Survival (PFS)
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Novartis Pharmaceuticals

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

Links úteis

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de julho de 2009

Conclusão Primária (Real)

1 de janeiro de 2014

Conclusão do estudo (Real)

1 de janeiro de 2014

Datas de inscrição no estudo

Enviado pela primeira vez

8 de abril de 2009

Enviado pela primeira vez que atendeu aos critérios de CQ

9 de abril de 2009

Primeira postagem (Estimativa)

10 de abril de 2009

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

3 de novembro de 2015

Última atualização enviada que atendeu aos critérios de controle de qualidade

8 de outubro de 2015

Última verificação

1 de outubro de 2015

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

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

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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