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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01041404




Registration number
NCT01041404
Ethics application status
Date submitted
29/12/2009
Date registered
31/12/2009
Date last updated
5/11/2014

Titles & IDs
Public title
ToGA Study - A Study of Herceptin (Trastuzumab) in Combination With Chemotherapy Compared With Chemotherapy Alone in Patients With HER2-Positive Advanced Gastric Cancer
Scientific title
A Randomized, Open-label Study of the Effect of First-line Herceptin in Combination With a Fluoropyrimidine and Cisplatin Versus Chemotherapy Alone on Overall Survival in Patients With HER2-positive Advanced Gastric Cancer
Secondary ID [1] 0 0
BO18255
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - Trastuzumab
Treatment: Drugs - Fluorouracil
Treatment: Drugs - Cisplatin
Treatment: Drugs - Capecitabine

Experimental: Trastuzumab, Fluoropyrimidine, Cisplatin - Participants received an initial loading dose of 8 milligrams per kilogram (mg/kg) trastuzumab i.v. on Day 1 of cycle, followed by 6 mg/kg i.v. every 3 weeks until disease progression; 800 mg/m2 fluorouracil i.v. on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine p.o. twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.

Active Comparator: Fluoropyrimidine, Cisplatin - Participants received 800 milligrams per square meter (mg/m2) fluorouracil intravenous (i.v.) on Days 1 through 5 of cycle every 3 weeks for 6 cycles; 80 mg/m2 cisplatin i.v. on Day 1 of cycle every 3 weeks for 6 cycles; and 1000 mg/m2 capecitabine orally (p.o.) twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles.


Treatment: Drugs: Trastuzumab
Initial loading dose 8 mg/kg i.v. infusion on Day 1 of cycle, followed by 6 mg/kg i.v. infusion every 3 weeks until disease progression

Treatment: Drugs: Fluorouracil
800 mg/m2 i.v. infusion on Days 1 through 5 of cycle every 3 weeks for 6 cycles

Treatment: Drugs: Cisplatin
80 mg/m2 i.v. infusion on Day 1 of cycle every 3 weeks for 6 cycles

Treatment: Drugs: Capecitabine
1000 mg/m2 p.o. twice daily on Days 1 through 15 of cycle every 3 weeks for 6 cycles

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

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - Percentage of Participants With an Event - OS was defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
Timepoint [1] 0 0
Baseline (BL), Days 1, 8, 15, 22, 43, 64, 85, 106, 127, and every 21 days until the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Primary outcome [2] 0 0
Overall Survival - Time to Event - The median time, in months, from the date of randomization to the date of an OS event. Participants were censored at the last date tumor measurement, the last date in the study drug log, or the date of last follow-up.
Timepoint [2] 0 0
BL, Days 1, 8, 15, 22, 43, 64, 85, 106, 127, and every 21 days until the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) - Percentage of Participants With an Event - PFS was defined as the time from the date of randomization to the date of the first documentation of progressive disease (PD) or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
Timepoint [1] 0 0
BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [2] 0 0
Progression-Free Survival - Time to Event - The median time, in months, from the date of randomization to the date of a PFS event. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
Timepoint [2] 0 0
BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [3] 0 0
Time to Progression (TTP) - Percentage of Participants With an Event - TTP was defined as the time from the date of randomization and the date of the first occurrence of PD. Participants were censored at the last date of tumor assessment, the last date in the study drug log, or the last date of follow-up.
Timepoint [3] 0 0
BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [4] 0 0
Time to Progression - Time to Event - The median time, in months, from the date of randomized to the date of a TTP event. Participants were censored at the last date of tumor assessment, the last date in the study drug log, or the last date of follow-up.
Timepoint [4] 0 0
BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [5] 0 0
Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) - For TLs, a CR was defined as the disappearance of all TLs and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels.
Timepoint [5] 0 0
BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [6] 0 0
Duration of Response - Percentage of Participants With an Event - Duration of response was defined for responders as the time from the date on which the CR or PR was first recorded to the date on which PD is first noted. Participants were censored on the date of death, the date of last tumor measurement, the last date in study drug log, or the date of last follow-up.
Timepoint [6] 0 0
BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [7] 0 0
Duration of Response - The median time, in months, of the duration of response. Participants were censored at the date of death, the date of last tumor measurement, the last date in study drug log, or the date of last follow-up.
Timepoint [7] 0 0
BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [8] 0 0
Percentage of Participants With Clinical Benefit - Clinical benefit was defined as stable disease (SD), CR, or PR for 6 weeks or longer as determined by RECIST. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD, taking as a reference the smallest SLD recorded since treatment had started. For NTLs, SD was defined as a persistence of one or more NTLs and/or maintenance of tumor marker levels above the normal limits.
Timepoint [8] 0 0
BL, Days 43, 85, and 127, and every 21 days thereafter until disease progression or the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [9] 0 0
European Organisation For the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ C-30) Questionnaire Scores - EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score equals (=) better level of functioning or greater degree of symptoms.
Timepoint [9] 0 0
BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [10] 0 0
EORTC Quality of Life Questionnaire-Stomach Cancer Specific (QLQ STO22) Questionnaire Scores - The QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). The questions are grouped into five scales and 4 single items which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.
Timepoint [10] 0 0
BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [11] 0 0
Pain Intensity Scores as Assessed By Visual Analog Scale (VAS) - The participant assessed their pain on a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.
Timepoint [11] 0 0
BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [12] 0 0
Percentage of Participants With a Change in Analgesic Medication During the Study - Analgesic medications were recorded throughout the study until disease progression.
Timepoint [12] 0 0
BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [13] 0 0
Body Weight (Kilograms [kg]) at BL
Timepoint [13] 0 0
BL
Secondary outcome [14] 0 0
Percentage of Participants With Change From Baseline in Body Weight by Percentage Change in Weight - Change in body weight was categorized as an increase of greater than (>)5 percent (%), no change (plus or minus [±]5%), decrease of >5-10%, or a decrease of >10% from BL to the end of study. Time windows were applied in order to assign visits to weight measurements, and the lowest post-screening value recorded was used for the analysis. The percentage change in weight from screening was summarized over time.
Timepoint [14] 0 0
BL, Days 1, 22, 43, 64, 85, 106, 127, and every 21 days until disease progression of the end of study, 1 year after the cut-off date for the 2nd interim efficacy analysis
Secondary outcome [15] 0 0
Steady State Trastuzumab Area Under the Concentration (AUC) - Individual steady state predicted exposure, as assessed by median AUC (measured as mg multiplied by [*] day per liter [L]) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion. Individual steady state AUC was calculated using all available PK samples from all timepoints.
Timepoint [15] 0 0
Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106
Secondary outcome [16] 0 0
Trastuzumab Minimum Serum Concentration (Cmin) - Median Cmin (measured as milligrams per liter [mg/L]) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion.
Timepoint [16] 0 0
Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106
Secondary outcome [17] 0 0
Trastuzumab Maximum Serum Concentration (Cmax) - Median Cmax (measured as mg/L) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion.
Timepoint [17] 0 0
Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106

Eligibility
Key inclusion criteria
- Adult patients >=18 years of age

- Inoperable locally advanced, recurrent, and/or metastatic cancer of the stomach or
gastro-esophageal junction

- Adenocarcinoma

- HER2-positive tumors
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous chemotherapy for advanced/metastatic disease

- Lack of physical integrity of the upper gastrointestinal tract, or malabsorption
syndrome

- History of cardiac disease

- Dyspnoea at rest, due to complications of advanced malignancy or other disease, or
patients who require supportive oxygen therapy

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
Open (masking not used)
Who is / are masked / blinded?



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)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Kurralta Park
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Milton
Recruitment hospital [5] 0 0
- Perth
Recruitment hospital [6] 0 0
- Sydney
Recruitment postcode(s) [1] 0 0
5011 - Adelaide
Recruitment postcode(s) [2] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [3] 0 0
3128 - Melbourne
Recruitment postcode(s) [4] 0 0
4064 - Milton
Recruitment postcode(s) [5] 0 0
6008 - Perth
Recruitment postcode(s) [6] 0 0
2217 - Sydney
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Leuven
Country [2] 0 0
Brazil
State/province [2] 0 0
Barretos
Country [3] 0 0
Brazil
State/province [3] 0 0
Rio de Janeiro
Country [4] 0 0
Brazil
State/province [4] 0 0
Sao Paulo
Country [5] 0 0
China
State/province [5] 0 0
Beijing
Country [6] 0 0
China
State/province [6] 0 0
Guangdong
Country [7] 0 0
China
State/province [7] 0 0
Guangzhou
Country [8] 0 0
China
State/province [8] 0 0
Jiangsu
Country [9] 0 0
China
State/province [9] 0 0
Nanjing
Country [10] 0 0
China
State/province [10] 0 0
Shanghai
Country [11] 0 0
China
State/province [11] 0 0
Suzhou
Country [12] 0 0
China
State/province [12] 0 0
Wuhan
Country [13] 0 0
Costa Rica
State/province [13] 0 0
San Jose
Country [14] 0 0
Costa Rica
State/province [14] 0 0
San José
Country [15] 0 0
Denmark
State/province [15] 0 0
Herlev
Country [16] 0 0
Denmark
State/province [16] 0 0
Odense
Country [17] 0 0
Finland
State/province [17] 0 0
Tampere
Country [18] 0 0
France
State/province [18] 0 0
Brest
Country [19] 0 0
France
State/province [19] 0 0
Caen
Country [20] 0 0
France
State/province [20] 0 0
Colmar
Country [21] 0 0
France
State/province [21] 0 0
Lille
Country [22] 0 0
France
State/province [22] 0 0
Marseille
Country [23] 0 0
France
State/province [23] 0 0
Reims
Country [24] 0 0
France
State/province [24] 0 0
Rouen
Country [25] 0 0
France
State/province [25] 0 0
Strasbourg
Country [26] 0 0
Germany
State/province [26] 0 0
Heidelberg
Country [27] 0 0
Germany
State/province [27] 0 0
Mainz
Country [28] 0 0
Germany
State/province [28] 0 0
München
Country [29] 0 0
Germany
State/province [29] 0 0
Trier
Country [30] 0 0
Germany
State/province [30] 0 0
Witten
Country [31] 0 0
Guatemala
State/province [31] 0 0
Guatemala City
Country [32] 0 0
India
State/province [32] 0 0
Hyderabad
Country [33] 0 0
India
State/province [33] 0 0
Kochi
Country [34] 0 0
India
State/province [34] 0 0
Mumbai
Country [35] 0 0
India
State/province [35] 0 0
New Delhi
Country [36] 0 0
Italy
State/province [36] 0 0
Ancona
Country [37] 0 0
Italy
State/province [37] 0 0
Firenze
Country [38] 0 0
Italy
State/province [38] 0 0
Napoli
Country [39] 0 0
Italy
State/province [39] 0 0
Parma
Country [40] 0 0
Italy
State/province [40] 0 0
Roma
Country [41] 0 0
Italy
State/province [41] 0 0
Udine
Country [42] 0 0
Japan
State/province [42] 0 0
Aichi
Country [43] 0 0
Japan
State/province [43] 0 0
Chiba
Country [44] 0 0
Japan
State/province [44] 0 0
Ehime
Country [45] 0 0
Japan
State/province [45] 0 0
Fukuoka
Country [46] 0 0
Japan
State/province [46] 0 0
Hyogo
Country [47] 0 0
Japan
State/province [47] 0 0
Nagano
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Saitama
Country [50] 0 0
Japan
State/province [50] 0 0
Shizuoka
Country [51] 0 0
Japan
State/province [51] 0 0
Tochigi
Country [52] 0 0
Japan
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Tokyo
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Japan
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Yamagata
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Korea, Republic of
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Buchun
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Korea, Republic of
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Bundang City
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Korea, Republic of
State/province [56] 0 0
Daegu
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Pusan
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Korea, Republic of
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Seoul
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Mexico
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Guadalajara
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Mexico
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Merida
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Mexico
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Mexico City
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Mexico
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Monterrey
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Panama
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Panama City
Country [65] 0 0
Peru
State/province [65] 0 0
Callao
Country [66] 0 0
Peru
State/province [66] 0 0
Lima
Country [67] 0 0
Portugal
State/province [67] 0 0
Braga
Country [68] 0 0
Portugal
State/province [68] 0 0
Coimbra
Country [69] 0 0
Portugal
State/province [69] 0 0
Faro
Country [70] 0 0
Portugal
State/province [70] 0 0
Guimaraes
Country [71] 0 0
Portugal
State/province [71] 0 0
Lisboa
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Portugal
State/province [72] 0 0
Porto
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Russian Federation
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Chelyabinsk
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Russian Federation
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Ekaterinburg
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Russian Federation
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Ivanovo
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
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Ryazan
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Russian Federation
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Samara
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Russian Federation
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St Petersburg
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Russian Federation
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UFA
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Russian Federation
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Yaroslavl
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South Africa
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Cape Town
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South Africa
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Durban
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Spain
State/province [85] 0 0
Barcelona
Country [86] 0 0
Spain
State/province [86] 0 0
Girona
Country [87] 0 0
Spain
State/province [87] 0 0
Madrid
Country [88] 0 0
Spain
State/province [88] 0 0
Valencia
Country [89] 0 0
Taiwan
State/province [89] 0 0
Changhua
Country [90] 0 0
Taiwan
State/province [90] 0 0
Kaohsiung
Country [91] 0 0
Taiwan
State/province [91] 0 0
Taipei
Country [92] 0 0
Turkey
State/province [92] 0 0
Istanbul
Country [93] 0 0
Turkey
State/province [93] 0 0
Izmir
Country [94] 0 0
Turkey
State/province [94] 0 0
Shhiye, Ankara
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Birmingham
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Denbigh
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Dundee
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Glasgow
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Manchester
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Weston Super Mare
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Wirral
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Chugai Pharmaceutical
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This parallel, randomized, open-label, multi-centre study will evaluate the effect on overall
survival of trastuzumab (Herceptin) in combination with a chemotherapy compared to the
chemotherapy alone in patients with HER2-positive advanced gastric cancer. Trastuzumab
(Herceptin) will be administered as intravenous infusion of 6 mg/kg (loading dose 8 mg/kg)
every 3 weeks. The chemotherapy consists of a combination of 6 cycles of fluorouracil (800
mg/m2/day intravenous infusion every 3 weeks) and cisplatin (80 mg/m2 intravenous infusion
every 3 weeks), or capecitabine (Xeloda, 1000 mg/m2 po twice daily for 14 days every 3 weeks)
and cisplatin (80 mg/m2 intravenous infusion every 3 weeks). Treatment with trastuzumab
(Herceptin) will continue until disease progression. The target sample size is 300-600
patients.
Trial website
https://clinicaltrials.gov/show/NCT01041404
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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