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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00879333




Registration number
NCT00879333
Ethics application status
Date submitted
8/04/2009
Date registered
9/04/2009
Date last updated
8/10/2015

Titles & IDs
Public title
Safety and Efficacy of RAD001 (Everolimus) Monotherapy Plus Best Supportive Care in Patients With Advanced Gastric Cancer (AGC)
Scientific title
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
Secondary ID [1] 0 0
2008-006544-20
Secondary ID [2] 0 0
CRAD001R2301
Universal Trial Number (UTN)
Trial acronym
GRANITE-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Gastric Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Everolimus
Treatment: Drugs - Everolimus placebo
Treatment: Drugs - Best Supportive Care (BSC)

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.

Placebo Comparator: 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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - 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.
Timepoint [1] 0 0
2.5 years
Secondary outcome [1] 0 0
Progression Free Survival (PFS) - 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.
Timepoint [1] 0 0
2.5 years
Secondary outcome [2] 0 0
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 - 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).
Timepoint [2] 0 0
2.5 years
Secondary outcome [3] 0 0
Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score - 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.
Timepoint [3] 0 0
2.5 years
Secondary outcome [4] 0 0
Overall Response Rate (ORR) - 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.
Timepoint [4] 0 0
2.5 years
Secondary outcome [5] 0 0
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax at 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.
Timepoint [5] 0 0
Week 5
Secondary outcome [6] 0 0
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax by Region Asia vs. Rest of the World (ROW) at 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.
Timepoint [6] 0 0
Week 5

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Canberra
Recruitment hospital [2] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [3] 0 0
Novartis Investigative Site - Kurralta Park
Recruitment hospital [4] 0 0
Novartis Investigative Site - North Adelaide
Recruitment hospital [5] 0 0
Novartis Investigative Site - Box Hill
Recruitment hospital [6] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [7] 0 0
Novartis Investigative Site - Footscray
Recruitment hospital [8] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [9] 0 0
Novartis Investigative Site - Prahran
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3011 - Footscray
Recruitment postcode(s) [8] 0 0
3084 - Heidelberg
Recruitment postcode(s) [9] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
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Washington
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Argentina
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Viedma
Country [8] 0 0
Argentina
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Buenos Aires
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Argentina
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Cordoba
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Belgium
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Charleroi
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Liege
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Canada
State/province [14] 0 0
British Columbia
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Canada
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Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
China
State/province [17] 0 0
Guangdong
Country [18] 0 0
China
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Hebei
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China
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Heilongjiang
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China
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Jiangsu
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China
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Liaoning
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China
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Sichuan
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China
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Zhejiang
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China
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Beijing
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China
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Guangzhou
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China
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Shanghai
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France
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Avignon Cedex
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France
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Clermont Ferrand cedex 1
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France
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Clichy
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France
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Dijon
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France
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Lyon Cedex 08
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France
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Marseille cedex 05
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France
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Montpellier Cedex 5
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France
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Nice Cedex 2
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France
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Paris
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France
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Pessac Cedex
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France
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Poitiers
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France
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Reims
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France
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Rennes Cedex
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France
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Toulouse Cedex 4
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France
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Villejuif Cedex
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Germany
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Baden-Württemberg
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Germany
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Berlin
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Germany
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Bielefeld
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Germany
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Frankfurt
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Germany
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Mainz
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Germany
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München
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Germany
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Offenburg
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Germany
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Trier
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Hong Kong
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Hong Kong SAR
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Israel
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Jerusalem
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Israel
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Petach Tikva
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Israel
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Ramat Gan
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Israel
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Rehovot
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Italy
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FI
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Italy
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MI
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Italy
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MO
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Italy
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PN
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Italy
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Frattamaggiore
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Japan
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Aichi
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Japan
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Chiba
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Ehime
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Fukuoka
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Hokkaido
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Kanagawa
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Miyagi
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Osaka
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Japan
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Saitama
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Japan
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Tochigi
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Japan
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Tokyo
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Korea, Republic of
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Jeollabuk-do
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Korea, Republic of
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Korea
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Korea, Republic of
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Seoul
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Korea, Republic of
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Taegu
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Mexico
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Distrito Federal
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Mexico
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Guanajuato
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Netherlands
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Amsterdam
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New Zealand
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Auckland
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Peru
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Lima
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Russian Federation
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Moscow
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Russian Federation
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St. Petersburg
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Spain
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Catalunya
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Taiwan
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Taoyuan/ Taiwan ROC
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Taiwan
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Liouying Township
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Taiwan
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Niaosong Township
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Taiwan
State/province [86] 0 0
Taipei
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Thailand
State/province [87] 0 0
Bangkok
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Thailand
State/province [88] 0 0
Songkla
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Middlesex
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United Kingdom
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Surrey
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United Kingdom
State/province [91] 0 0
East Yorkshire
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
State/province [94] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00879333
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications