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Safety and Efficacy of RAD001 (Everolimus) Monotherapy Plus Best Supportive Care in Patients With Advanced Gastric Cancer (AGC) (GRANITE-1)

2015年10月8日 更新者：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.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

656

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 中国
      • Beijing、中国、100039
        • Novartis Investigative Site
      • Beijing、中国、100036
        • Novartis Investigative Site
      • Guangzhou、中国、510060
        • Novartis Investigative Site
      • Shanghai、中国、200032
        • Novartis Investigative Site
      • Shanghai、中国、200003
        • Novartis Investigative Site
      • Shanghai、中国、200025
        • Novartis Investigative Site
    • Guangdong
      • Guangzhou、Guangdong、中国、510515
        • Novartis Investigative Site
    • Hebei
      • Shijiazhuang、Hebei、中国、050011
        • Novartis Investigative Site
    • Heilongjiang
      • Harbin、Heilongjiang、中国、150081
        • Novartis Investigative Site
    • Jiangsu
      • Nanjing、Jiangsu、中国、210002
        • Novartis Investigative Site
      • Suzhou、Jiangsu、中国、215006
        • Novartis Investigative Site
    • Liaoning
      • Shenyang、Liaoning、中国
        • Novartis Investigative Site
    • Sichuan
      • Chengdu、Sichuan、中国、610041
        • Novartis Investigative Site
    • Zhejiang
      • Hangzhou、Zhejiang、中国、310016
        • Novartis Investigative Site
  • 以色列
      • Jerusalem、以色列、9112001
        • Novartis Investigative Site
      • Petach Tikva、以色列、49100
        • Novartis Investigative Site
      • Ramat Gan、以色列、5266202
        • Novartis Investigative Site
      • Rehovot、以色列、76100
        • Novartis Investigative Site
  • 俄罗斯联邦
      • Moscow、俄罗斯联邦、115478
        • Novartis Investigative Site
      • St. Petersburg、俄罗斯联邦、197758
        • Novartis Investigative Site
  • 加拿大
    • British Columbia
      • North Vancouver、British Columbia、加拿大、V7L 2L7
        • Novartis Investigative Site
      • Vancouver、British Columbia、加拿大、V5Z 4E6
        • Novartis Investigative Site
    • Ontario
      • Toronto、Ontario、加拿大、M4N 3M5
        • Novartis Investigative Site
      • Toronto、Ontario、加拿大、M5B 1W8
        • Novartis Investigative Site
    • Quebec
      • Montreal、Quebec、加拿大、H3G 1A4
        • Novartis Investigative Site
      • Sherbrooke、Quebec、加拿大、J1H 5N4
        • Novartis Investigative Site
  • 台湾
      • Liouying Township、台湾
        • Novartis Investigative Site
      • Niaosong Township、台湾、83301
        • Novartis Investigative Site
      • Taipei、台湾、10048
        • Novartis Investigative Site
      • Taipei、台湾
        • Novartis Investigative Site
    • Taoyuan/ Taiwan ROC
      • Kuei-Shan Chiang、Taoyuan/ Taiwan ROC、台湾、33305
        • Novartis Investigative Site
  • 墨西哥
    • Distrito Federal
      • México、Distrito Federal、墨西哥、14080
        • Novartis Investigative Site
    • Guanajuato
      • León、Guanajuato、墨西哥、37000
        • Novartis Investigative Site
  • 大韩民国
      • Seoul、大韩民国、136-705
        • Novartis Investigative Site
      • Taegu、大韩民国、700 - 721
        • Novartis Investigative Site
    • Jeollabuk-do
      • Jeonju-si、Jeollabuk-do、大韩民国、561-712
        • Novartis Investigative Site
    • Korea
      • Seoul、Korea、大韩民国、05505
        • Novartis Investigative Site
      • Seoul、Korea、大韩民国、06351
        • Novartis Investigative Site
      • Seoul、Korea、大韩民国、110 744
        • Novartis Investigative Site
      • Seoul、Korea、大韩民国、03722
        • Novartis Investigative Site
  • 德国
      • Berlin、德国、13353
        • Novartis Investigative Site
      • Bielefeld、德国、33604
        • Novartis Investigative Site
      • Frankfurt、德国、60488
        • Novartis Investigative Site
      • Mainz、德国、55131
        • Novartis Investigative Site
      • München、德国、81675
        • Novartis Investigative Site
      • Offenburg、德国、77652
        • Novartis Investigative Site
      • Trier、德国、54290
        • Novartis Investigative Site
    • Baden-Württemberg
      • Mannheim、Baden-Württemberg、德国、68305
        • Novartis Investigative Site
  • 意大利
      • Frattamaggiore、意大利、80020
        • Novartis Investigative Site
    • FI
      • Firenze、FI、意大利、50134
        • Novartis Investigative Site
    • MI
      • Rozzano、MI、意大利、20089
        • Novartis Investigative Site
    • MO
      • Modena、MO、意大利、41100
        • Novartis Investigative Site
    • PN
      • Aviano、PN、意大利、33081
        • Novartis Investigative Site
  • 新西兰
      • Auckland、新西兰
        • Novartis Investigative Site
  • 日本
    • Aichi
      • Nagoya、Aichi、日本、464-8681
        • Novartis Investigative Site
    • Chiba
      • Kashiwa、Chiba、日本、277-8577
        • Novartis Investigative Site
    • Ehime
      • Matsuyama、Ehime、日本、791-0280
        • Novartis Investigative Site
    • Fukuoka
      • Fukuoka-city、Fukuoka、日本、812-8582
        • Novartis Investigative Site
    • Hokkaido
      • Sapporo-city、Hokkaido、日本、060-8648
        • Novartis Investigative Site
    • Kanagawa
      • Sagamihara、Kanagawa、日本、252-0380
        • Novartis Investigative Site
    • Miyagi
      • Sendai-city、Miyagi、日本、980-8574
        • Novartis Investigative Site
    • Osaka
      • OsakaSayama、Osaka、日本、589-8511
        • Novartis Investigative Site
      • Takatsuki-city、Osaka、日本、569-8686
        • Novartis Investigative Site
    • Saitama
      • Kitaadachi-gun、Saitama、日本、362-0806
        • Novartis Investigative Site
    • Tochigi
      • Utsunomiya、Tochigi、日本、320-0834
        • Novartis Investigative Site
    • Tokyo
      • Chuo-ku、Tokyo、日本、104-0045
        • Novartis Investigative Site
      • Koto、Tokyo、日本、135-8550
        • Novartis Investigative Site
      • Mitaka-city、Tokyo、日本、181-8611
        • Novartis Investigative Site
  • 比利时
      • Charleroi、比利时、6000
        • Novartis Investigative Site
      • Gent、比利时、9000
        • Novartis Investigative Site
      • Leuven、比利时、3000
        • Novartis Investigative Site
      • Liege、比利时、4000
        • Novartis Investigative Site
  • 法国
      • Avignon Cedex、法国、84082
        • Novartis Investigative Site
      • Clermont Ferrand cedex 1、法国、63003
        • Novartis Investigative Site
      • Clichy、法国、92110
        • Novartis Investigative Site
      • Dijon、法国、21079
        • Novartis Investigative Site
      • Lyon Cedex 08、法国、69373
        • Novartis Investigative Site
      • Marseille cedex 05、法国、13385
        • Novartis Investigative Site
      • Montpellier Cedex 5、法国、34298
        • Novartis Investigative Site
      • Nice Cedex 2、法国、06189
        • Novartis Investigative Site
      • Paris、法国、75015
        • Novartis Investigative Site
      • Pessac Cedex、法国、33604
        • Novartis Investigative Site
      • Poitiers、法国、86000
        • Novartis Investigative Site
      • Reims、法国、51092
        • Novartis Investigative Site
      • Rennes Cedex、法国、35062
        • Novartis Investigative Site
      • Toulouse Cedex 4、法国、31054
        • Novartis Investigative Site
      • Villejuif Cedex、法国、94805
        • Novartis Investigative Site
  • 泰国
      • Bangkok、泰国、10700
        • Novartis Investigative Site
      • Bangkok、泰国、10400
        • Novartis Investigative Site
      • Songkla、泰国、90110
        • Novartis Investigative Site
  • 澳大利亚
    • Australian Capital Territory
      • Canberra、Australian Capital Territory、澳大利亚、2605
        • Novartis Investigative Site
    • Queensland
      • Herston、Queensland、澳大利亚、4029
        • Novartis Investigative Site
    • South Australia
      • Kurralta Park、South Australia、澳大利亚、5037
        • Novartis Investigative Site
      • North Adelaide、South Australia、澳大利亚、5006
        • Novartis Investigative Site
    • Victoria
      • Box Hill、Victoria、澳大利亚、3128
        • Novartis Investigative Site
      • Clayton、Victoria、澳大利亚、3168
        • Novartis Investigative Site
      • Footscray、Victoria、澳大利亚、3011
        • Novartis Investigative Site
      • Heidelberg、Victoria、澳大利亚、3084
        • Novartis Investigative Site
      • Prahran、Victoria、澳大利亚、3181
        • Novartis Investigative Site
  • 秘鲁
    • Lima
      • San Borja、Lima、秘鲁、41
        • Novartis Investigative Site
      • San Isidro、Lima、秘鲁、27
        • Novartis Investigative Site
  • 美国
    • Arkansas
      • Fayetteville、Arkansas、美国、72703
        • Highlands Oncology Group DeptofHighlandsOncologyGrp(2)
    • California
      • Redlands、California、美国、92374
        • Loma Linda Oncology Medical Group Loma Linda
    • Michigan
      • Detroit、Michigan、美国、48202-2689
        • Henry Ford Hospital Dept. of Henry Ford Hospital
    • Minnesota
      • Minneapolis、Minnesota、美国、55455
        • University of Minnesota Cancer Center
    • Texas
      • Dallas、Texas、美国、75390-8527
        • University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(4)
      • Fort Worth、Texas、美国、76104
        • The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
      • Houston、Texas、美国、77030-4009
        • University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
    • Washington
      • Seattle、Washington、美国、98109-1023
        • University of Washington Cancer Care Seattle Cancer Alliance
  • 英国
      • East Yorkshire、英国、HU16 5JQ
        • Novartis Investigative Site
      • London、英国、SW3 6JJ
        • Novartis Investigative Site
      • London、英国、WC1E 6HX
        • Novartis Investigative Site
      • Manchester、英国、M20 4BX
        • Novartis Investigative Site
      • Wolverhampton、英国、WV10 0QP
        • Novartis Investigative Site
    • Middlesex
      • Northwood、Middlesex、英国、HA6 2RN
        • Novartis Investigative Site
    • Surrey
      • Sutton、Surrey、英国、SM2 5PT
        • Novartis Investigative Site
  • 荷兰
      • Amsterdam、荷兰、1105 AZ
        • Novartis Investigative Site
  • 西班牙
    • Catalunya
      • Barcelona、Catalunya、西班牙、08035
        • Novartis Investigative Site
  • 阿根廷
      • Buenos Aires、阿根廷、C1264AAA
        • Novartis Investigative Site
      • Cordoba、阿根廷、X5000IUG
        • Novartis Investigative Site
    • Viedma
      • Rio Negro、Viedma、阿根廷、8500
        • Novartis Investigative Site
  • 香港
      • Hong Kong SAR、香港
        • Novartis Investigative Site

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：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.
药品：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.
其他名称：
  • RAD001
药品：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.
安慰剂比较：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.
药品：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.
药品：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.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Overall Survival (OS)
大体时间：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

次要结果测量

结果测量
措施说明
大体时间
Progression Free Survival (PFS)
大体时间：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
大体时间：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
大体时间：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)
大体时间：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
大体时间：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
大体时间：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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Novartis Pharmaceuticals

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2009年7月1日

初级完成 (实际的)

2014年1月1日

研究完成 (实际的)

2014年1月1日

研究注册日期

首次提交

2009年4月8日

首先提交符合 QC 标准的

2009年4月9日

首次发布 (估计)

2009年4月10日

研究记录更新

最后更新发布 (估计)

2015年11月3日

上次提交的符合 QC 标准的更新

2015年10月8日

最后验证

2015年10月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

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

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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