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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
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
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
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
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
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)
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
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
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
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
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
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)
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
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
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)
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)
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)
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
Sex
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
1/09/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2010
Sample size
Target
Accrual to date
Final
584
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
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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
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Nagano
Country [48] 0 0
Japan
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Osaka
Country [49] 0 0
Japan
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Saitama
Country [50] 0 0
Japan
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Shizuoka
Country [51] 0 0
Japan
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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
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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
State/province [59] 0 0
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
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Peru
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Callao
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Peru
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Lima
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Portugal
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Braga
Country [68] 0 0
Portugal
State/province [68] 0 0
Coimbra
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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
Country [72] 0 0
Portugal
State/province [72] 0 0
Porto
Country [73] 0 0
Russian Federation
State/province [73] 0 0
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
Country [80] 0 0
Russian Federation
State/province [80] 0 0
St Petersburg
Country [81] 0 0
Russian Federation
State/province [81] 0 0
UFA
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Russian Federation
State/province [82] 0 0
Yaroslavl
Country [83] 0 0
South Africa
State/province [83] 0 0
Cape Town
Country [84] 0 0
South Africa
State/province [84] 0 0
Durban
Country [85] 0 0
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/study/NCT01041404
Trial related presentations / publications
Van Cutsem E, Bang YJ, Feng-Yi F, Xu JM, Lee KW, Jiao SC, Chong JL, Lopez-Sanchez RI, Price T, Gladkov O, Stoss O, Hill J, Ng V, Lehle M, Thomas M, Kiermaier A, Ruschoff J. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015 Jul;18(3):476-84. doi: 10.1007/s10120-014-0402-y. Epub 2014 Jul 20.
Satoh T, Bang YJ, Gotovkin EA, Hamamoto Y, Kang YK, Moiseyenko VM, Ohtsu A, Van Cutsem E, Al-Sakaff N, Urspruch A, Hill J, Weber HA, Chung HC; ToGA Trial Investigators. Quality of life in the trastuzumab for gastric cancer trial. Oncologist. 2014 Jul;19(7):712-9. doi: 10.1634/theoncologist.2014-0058. Epub 2014 Jun 20.
Satoh T, Omuro Y, Sasaki Y, Hamamoto Y, Boku N, Tamura T, Ohtsu A. Pharmacokinetic analysis of capecitabine and cisplatin in combination with trastuzumab in Japanese patients with advanced HER2-positive gastric cancer. Cancer Chemother Pharmacol. 2012 Apr;69(4):949-55. doi: 10.1007/s00280-011-1783-9. Epub 2011 Nov 25.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19. Erratum In: Lancet. 2010 Oct 16;376(9749):1302.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01041404