Clinical trial NCT01041404: ToGA Study - A Study of Herceptin (Trastuzumab) in Combination With Chemotherapy Compared With Chemotherapy Alone in Patients With HER2-Positive Advanced Gastric Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Chugai Pharmaceutical
First posted: 2009-12-31
Enrollment: 584
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Overall Survival (OS) - Percentage of Participants With an Event
timeFrame: 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
measure: Overall Survival - Time to Event
timeFrame: 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 outcomes:
measure: Progression-Free Survival (PFS) - Percentage of Participants With an Event
timeFrame: 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
measure: Progression-Free Survival - Time to Event
timeFrame: 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
measure: Time to Progression (TTP) - Percentage of Participants With an Event
timeFrame: 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
measure: Time to Progression - Time to Event
timeFrame: 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
measure: Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: 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
measure: Duration of Response - Percentage of Participants With an Event
timeFrame: 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
measure: Duration of Response
timeFrame: 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
measure: Percentage of Participants With Clinical Benefit
timeFrame: 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
measure: European Organisation For the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ C-30) Questionnaire Scores
timeFrame: 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
measure: EORTC Quality of Life Questionnaire-Stomach Cancer Specific (QLQ STO22) Questionnaire Scores
timeFrame: 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
measure: Pain Intensity Scores as Assessed By Visual Analog Scale (VAS)
timeFrame: 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
measure: Percentage of Participants With a Change in Analgesic Medication During the Study
timeFrame: 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
measure: Body Weight (Kilograms [kg]) at BL
timeFrame: BL
measure: Percentage of Participants With Change From Baseline in Body Weight by Percentage Change in Weight
timeFrame: 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
measure: Steady State Trastuzumab Area Under the Concentration (AUC)
timeFrame: Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106
measure: Trastuzumab Minimum Serum Concentration (Cmin)
timeFrame: Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106
measure: Trastuzumab Maximum Serum Concentration (Cmax)
timeFrame: Predose and end of infusion on Days 1, 8, 15, and 64, and predose on Days 22 and 106
Other outcomes:
Locations:
city: Adelaide
country: Australia
city: Kurralta Park
country: Australia
city: Melbourne
country: Australia
city: Milton
country: Australia
city: Perth
country: Australia
city: Sydney
country: Australia
city: Leuven
country: Belgium
city: Barretos
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Sao Paulo
country: Brazil
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Guangdong
country: China
city: Guangzhou
country: China
city: Jiangsu
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Suzhou
country: China
city: Wuhan
country: China
city: San Jose
country: Costa Rica
city: San José
country: Costa Rica
city: Herlev
country: Denmark
city: Odense
country: Denmark
city: Tampere
country: Finland
city: Brest
country: France
city: Caen
country: France
city: Colmar
country: France
city: Lille
country: France
city: Marseille
country: France
city: Reims
country: France
city: Rouen
country: France
city: Strasbourg
country: France
city: Heidelberg
country: Germany
city: Mainz
country: Germany
city: München
country: Germany
city: Trier
country: Germany
city: Witten
country: Germany
city: Guatemala City
country: Guatemala
city: Hyderabad
country: India
city: Kochi
country: India
city: Mumbai
country: India
city: New Delhi
country: India
city: Ancona
country: Italy
city: Firenze
country: Italy
city: Napoli
country: Italy
city: Parma
country: Italy
city: Roma
country: Italy
city: Udine
country: Italy
city: Aichi
country: Japan
city: Chiba
country: Japan
city: Ehime
country: Japan
city: Fukuoka
country: Japan
city: Hyogo
country: Japan
city: Nagano
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Saitama
country: Japan
city: Saitama
country: Japan
city: Shizuoka
country: Japan
city: Tochigi
country: Japan
city: Tokyo
country: Japan
city: Tokyo
country: Japan
city: Tokyo
country: Japan
city: Yamagata
country: Japan
city: Buchun
country: Korea, Republic of
city: Bundang City
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Goyang-si
country: Korea, Republic of
city: Pusan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Guadalajara
country: Mexico
city: Merida
country: Mexico
city: Mexico City
country: Mexico
city: Mexico City
country: Mexico
city: Monterrey
country: Mexico
city: Panama City
country: Panama
city: Callao
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Braga
country: Portugal
city: Coimbra
country: Portugal
city: Faro
country: Portugal
city: Guimaraes
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Porto
country: Portugal
city: Porto
country: Portugal
city: Chelyabinsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Kazan
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Samara
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: UFA
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Cape Town
country: South Africa
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Girona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Changhua
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Taipei
country: Taiwan
city: Istanbul
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Izmir
country: Turkey
city: Shhiye, Ankara
country: Turkey
city: Birmingham
country: United Kingdom
city: Denbigh
country: United Kingdom
city: Dundee
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Manchester
country: United Kingdom
city: Weston Super Mare
country: United Kingdom
city: Wirral
country: United Kingdom
city: Wolverhampton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.