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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 octubre de 2015 actualizado 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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

656

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Alemania
      • Berlin, Alemania, 13353
        • Novartis Investigative Site
      • Bielefeld, Alemania, 33604
        • Novartis Investigative Site
      • Frankfurt, Alemania, 60488
        • Novartis Investigative Site
      • Mainz, Alemania, 55131
        • Novartis Investigative Site
      • München, Alemania, 81675
        • Novartis Investigative Site
      • Offenburg, Alemania, 77652
        • Novartis Investigative Site
      • Trier, Alemania, 54290
        • Novartis Investigative Site
    • Baden-Württemberg
      • Mannheim, Baden-Württemberg, Alemania, 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
  • Australia
    • Australian Capital Territory
      • Canberra, Australian Capital Territory, Australia, 2605
        • Novartis Investigative Site
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Novartis Investigative Site
    • South Australia
      • Kurralta Park, South Australia, Australia, 5037
        • Novartis Investigative Site
      • North Adelaide, South Australia, Australia, 5006
        • Novartis Investigative Site
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Novartis Investigative Site
      • Clayton, Victoria, Australia, 3168
        • Novartis Investigative Site
      • Footscray, Victoria, Australia, 3011
        • Novartis Investigative Site
      • Heidelberg, Victoria, Australia, 3084
        • Novartis Investigative Site
      • Prahran, Victoria, Australia, 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
  • Corea, república de
      • Seoul, Corea, república de, 136-705
        • Novartis Investigative Site
      • Taegu, Corea, república de, 700 - 721
        • Novartis Investigative Site
    • Jeollabuk-do
      • Jeonju-si, Jeollabuk-do, Corea, república de, 561-712
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Corea, república de, 05505
        • Novartis Investigative Site
      • Seoul, Korea, Corea, república de, 06351
        • Novartis Investigative Site
      • Seoul, Korea, Corea, república de, 110 744
        • Novartis Investigative Site
      • Seoul, Korea, Corea, república de, 03722
        • Novartis Investigative Site
  • España
    • Catalunya
      • Barcelona, Catalunya, España, 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
  • Federación Rusa
      • Moscow, Federación Rusa, 115478
        • Novartis Investigative Site
      • St. Petersburg, Federación Rusa, 197758
        • Novartis Investigative Site
  • Francia
      • Avignon Cedex, Francia, 84082
        • Novartis Investigative Site
      • Clermont Ferrand cedex 1, Francia, 63003
        • Novartis Investigative Site
      • Clichy, Francia, 92110
        • Novartis Investigative Site
      • Dijon, Francia, 21079
        • Novartis Investigative Site
      • Lyon Cedex 08, Francia, 69373
        • Novartis Investigative Site
      • Marseille cedex 05, Francia, 13385
        • Novartis Investigative Site
      • Montpellier Cedex 5, Francia, 34298
        • Novartis Investigative Site
      • Nice Cedex 2, Francia, 06189
        • Novartis Investigative Site
      • Paris, Francia, 75015
        • Novartis Investigative Site
      • Pessac Cedex, Francia, 33604
        • Novartis Investigative Site
      • Poitiers, Francia, 86000
        • Novartis Investigative Site
      • Reims, Francia, 51092
        • Novartis Investigative Site
      • Rennes Cedex, Francia, 35062
        • Novartis Investigative Site
      • Toulouse Cedex 4, Francia, 31054
        • Novartis Investigative Site
      • Villejuif Cedex, Francia, 94805
        • 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
  • Italia
      • Frattamaggiore, Italia, 80020
        • Novartis Investigative Site
    • FI
      • Firenze, FI, Italia, 50134
        • Novartis Investigative Site
    • MI
      • Rozzano, MI, Italia, 20089
        • Novartis Investigative Site
    • MO
      • Modena, MO, Italia, 41100
        • Novartis Investigative Site
    • PN
      • Aviano, PN, Italia, 33081
        • Novartis Investigative Site
  • Japón
    • Aichi
      • Nagoya, Aichi, Japón, 464-8681
        • Novartis Investigative Site
    • Chiba
      • Kashiwa, Chiba, Japón, 277-8577
        • Novartis Investigative Site
    • Ehime
      • Matsuyama, Ehime, Japón, 791-0280
        • Novartis Investigative Site
    • Fukuoka
      • Fukuoka-city, Fukuoka, Japón, 812-8582
        • Novartis Investigative Site
    • Hokkaido
      • Sapporo-city, Hokkaido, Japón, 060-8648
        • Novartis Investigative Site
    • Kanagawa
      • Sagamihara, Kanagawa, Japón, 252-0380
        • Novartis Investigative Site
    • Miyagi
      • Sendai-city, Miyagi, Japón, 980-8574
        • Novartis Investigative Site
    • Osaka
      • OsakaSayama, Osaka, Japón, 589-8511
        • Novartis Investigative Site
      • Takatsuki-city, Osaka, Japón, 569-8686
        • Novartis Investigative Site
    • Saitama
      • Kitaadachi-gun, Saitama, Japón, 362-0806
        • Novartis Investigative Site
    • Tochigi
      • Utsunomiya, Tochigi, Japón, 320-0834
        • Novartis Investigative Site
    • Tokyo
      • Chuo-ku, Tokyo, Japón, 104-0045
        • Novartis Investigative Site
      • Koto, Tokyo, Japón, 135-8550
        • Novartis Investigative Site
      • Mitaka-city, Tokyo, Japón, 181-8611
        • Novartis Investigative Site
  • México
    • Distrito Federal
      • México, Distrito Federal, México, 14080
        • Novartis Investigative Site
    • Guanajuato
      • León, Guanajuato, México, 37000
        • Novartis Investigative Site
  • Nueva Zelanda
      • Auckland, Nueva Zelanda
        • Novartis Investigative Site
  • Países Bajos
      • Amsterdam, Países Bajos, 1105 AZ
        • Novartis Investigative Site
  • Perú
    • Lima
      • San Borja, Lima, Perú, 41
        • Novartis Investigative Site
      • San Isidro, Lima, Perú, 27
        • Novartis Investigative Site
  • Porcelana
      • Beijing, Porcelana, 100039
        • Novartis Investigative Site
      • Beijing, Porcelana, 100036
        • Novartis Investigative Site
      • Guangzhou, Porcelana, 510060
        • Novartis Investigative Site
      • Shanghai, Porcelana, 200032
        • Novartis Investigative Site
      • Shanghai, Porcelana, 200003
        • Novartis Investigative Site
      • Shanghai, Porcelana, 200025
        • Novartis Investigative Site
    • Guangdong
      • Guangzhou, Guangdong, Porcelana, 510515
        • Novartis Investigative Site
    • Hebei
      • Shijiazhuang, Hebei, Porcelana, 050011
        • Novartis Investigative Site
    • Heilongjiang
      • Harbin, Heilongjiang, Porcelana, 150081
        • Novartis Investigative Site
    • Jiangsu
      • Nanjing, Jiangsu, Porcelana, 210002
        • Novartis Investigative Site
      • Suzhou, Jiangsu, Porcelana, 215006
        • Novartis Investigative Site
    • Liaoning
      • Shenyang, Liaoning, Porcelana
        • Novartis Investigative Site
    • Sichuan
      • Chengdu, Sichuan, Porcelana, 610041
        • Novartis Investigative Site
    • Zhejiang
      • Hangzhou, Zhejiang, Porcelana, 310016
        • 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
  • Tailandia
      • Bangkok, Tailandia, 10700
        • Novartis Investigative Site
      • Bangkok, Tailandia, 10400
        • Novartis Investigative Site
      • Songkla, Tailandia, 90110
        • Novartis Investigative Site
  • Taiwán
      • Liouying Township, Taiwán
        • Novartis Investigative Site
      • Niaosong Township, Taiwán, 83301
        • Novartis Investigative Site
      • Taipei, Taiwán, 10048
        • Novartis Investigative Site
      • Taipei, Taiwán
        • Novartis Investigative Site
    • Taoyuan/ Taiwan ROC
      • Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwán, 33305
        • Novartis Investigative Site

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
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.
Droga: 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.
Otros nombres:
  • RAD001
Droga: 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 placebos: 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.
Droga: 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.
Droga: 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.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Overall Survival (OS)
Periodo de tiempo: 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 resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Progression Free Survival (PFS)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Novartis Pharmaceuticals

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Enlaces Útiles

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de julio de 2009

Finalización primaria (Actual)

1 de enero de 2014

Finalización del estudio (Actual)

1 de enero de 2014

Fechas de registro del estudio

Enviado por primera vez

8 de abril de 2009

Primero enviado que cumplió con los criterios de control de calidad

9 de abril de 2009

Publicado por primera vez (Estimar)

10 de abril de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

3 de noviembre de 2015

Última actualización enviada que cumplió con los criterios de control de calidad

8 de octubre de 2015

Última verificación

1 de octubre de 2015

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

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

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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