ToGA Study - A Study of Herceptin (Trastuzumab) in Combination With Chemotherapy Compared With Chemotherapy Alone in Patients With HER2-Positive Advanced Gastric Cancer

NCT01041404 | Completed Phase 3 Results

• 1 other identifier: BO18255
• Study Type: interventional
• Target: 584
• Locations: 24 countries
• Sites: 142

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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

• 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.

  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 (17)

• Progression-Free Survival (PFS) - Percentage of Participants With an Event

  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

• Progression-Free Survival - Time to Event

  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

• Time to Progression (TTP) - Percentage of Participants With an Event

  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

• Time to Progression - Time to Event

  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

• Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)

  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

Study Arms (2)

Trastuzumab, Fluoropyrimidine, Cisplatin

EXPERIMENTAL

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.

Drug: Trastuzumab; Drug: Fluorouracil; Drug: Cisplatin; Drug: Capecitabine

Fluoropyrimidine, Cisplatin

ACTIVE COMPARATOR

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.

Drug: Fluorouracil; Drug: Cisplatin; Drug: Capecitabine

Interventions

Trastuzumab DRUG

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

Also known as: Herceptin

Trastuzumab, Fluoropyrimidine, Cisplatin

Fluorouracil DRUG

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

Also known as: 5-FU

Fluoropyrimidine, Cisplatin; Trastuzumab, Fluoropyrimidine, Cisplatin

Cisplatin DRUG

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

Fluoropyrimidine, Cisplatin; Trastuzumab, Fluoropyrimidine, Cisplatin

Capecitabine DRUG

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

Also known as: Xeloda

Fluoropyrimidine, Cisplatin; Trastuzumab, Fluoropyrimidine, Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Chugai Pharmaceutical: collaborator

Study Sites (142)

Unknown Facility

Adelaide, 5011, Australia

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Kurralta Park, 5037, Australia

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Melbourne, 3128, Australia

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Milton, 4064, Australia

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Perth, 6008, Australia

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Sydney, 2217, Australia

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Leuven, 3000, Belgium

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Barretos, 14784-400, Brazil

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Rio de Janeiro, 20231-050, Brazil

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São Paulo, 04023-900, Brazil

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São Paulo, 05403-010, Brazil

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Beijing, 100021, China

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Beijing, 100036, China

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Beijing, 100071, China

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Beijing, 100853, China

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Guangdong, 510515, China

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Guangzhou, 510060, China

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Jiangsu, 210009, China

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Nanjing, 210002, China

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Shanghai, 200003, China

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Shanghai, 200025, China

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Shanghai, 200032, China

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Shanghai, 200080, China

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Shanghai, 200092, China

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Shanghai, 200433, China

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Suzhou, 215006, China

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Wuhan, 430030, China

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San José, 10103, Costa Rica

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San José, Costa Rica

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Herlev, 2730, Denmark

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Odense, 5000, Denmark

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Tampere, 33520, Finland

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Brest, 29609, France

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Caen, 14076, France

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Colmar, 68024, France

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Lille, 59020, France

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Marseille, 13273, France

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Reims, 51092, France

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Rouen, 76031, France

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Strasbourg, 67098, France

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Heidelberg, 69120, Germany

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Mainz, 55101, Germany

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München, 81675, Germany

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Trier, 54290, Germany

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Witten, 58455, Germany

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Guatemala City, 01015, Guatemala

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Hyderabad, 500 033, India

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Kochi, 682304, India

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Mumbai, 400026, India

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New Delhi, 110 029, India

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Ancona, 60121, Italy

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Florence, 50139, Italy

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Napoli, 80131, Italy

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Parma, 43100, Italy

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Roma, 00168, Italy

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Udine, 33100, Italy

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Aichi, 464-8681, Japan

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Chiba, 277-8577, Japan

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Ehime, 791-0280, Japan

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Fukuoka, 812-8582, Japan

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Hyōgo, 650-0017, Japan

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Nagano, 384-0392, Japan

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Osaka, 569-8686, Japan

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Osaka, 589-8511, Japan

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Saitama, 350-1298, Japan

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Saitama, 362-0806, Japan

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Shizuoka, 411-8777, Japan

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Tochigi, 320-0834, Japan

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Tokyo, 113-8677, Japan

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Tokyo, 135-8550, Japan

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Tokyo, 135-8577, Japan

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Yamagata, 990-8520, Japan

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Guadalajara, 44280, Mexico

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Mexico City, 06760, Mexico

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Mexico City, 14000, Mexico

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Mérida, 97500, Mexico

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Monterrey, 64020, Mexico

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Panama City, Panama

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Callao, Peru

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Lima, 11, Peru

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Lima, 18, Peru

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Braga, 4700, Portugal

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Coimbra, 3000-075, Portugal

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Faro, 8000, Portugal

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Guimarães, 4810-055, Portugal

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Lisbon, 1099-023, Portugal

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Lisbon, 1649-035, Portugal

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Porto, 4099-001, Portugal

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Porto, 4200-072, Portugal

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Porto, 4200-319, Portugal

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Chelyabinsk, 454 087, Russia

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Ivanovo, 153040, Russia

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Kazan', 420029, Russia

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Moscow, 115478, Russia

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Moscow, 117837, Russia

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Moscow, 125284, Russia

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Moscow, 129128, Russia

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Ryazan, 390011, Russia

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Saint Petersburg, 195067, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197758, Russia

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Samara, 443031, Russia

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Ufa, 450054, Russia

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Yaroslavl, 150054, Russia

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Yekaterinburg, 620905, Russia

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Cape Town, 1925, South Africa

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Cape Town, 7506, South Africa

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Durban, 4091, South Africa

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Buchun, 420-021, South Korea

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Bundang City, 463-802, South Korea

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Daegu, 702-210, South Korea

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Goyang-si, 410-769, South Korea

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Pusan, 602-715, South Korea

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Seoul, 110-744, South Korea

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Seoul, 120-752, South Korea

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Seoul, 135-170, South Korea

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Seoul, 135-720, South Korea

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Seoul, 138-736, South Korea

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Seoul, South Korea

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Barcelona, 08036, Spain

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Barcelona, 08041, Spain

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Barcelona, 08907, Spain

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Girona, 17007, Spain

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Madrid, 28041, Spain

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Valencia, 41014, Spain

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Valencia, 46009, Spain

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Changhua, 500, Taiwan

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Kaohsiung City, 807, Taiwan

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Taipei, 00112, Taiwan

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Istanbul, 34300, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Shhiye, Ankara, 06100, Turkey (Türkiye)

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Birmingham, B9 5SS, United Kingdom

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Denbigh, LL18 5UJ, United Kingdom

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Dundee, DD1 9SY, United Kingdom

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Glasgow, G12 0YN, United Kingdom

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Manchester, M2O 4BX, United Kingdom

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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

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Weston-super-Mare, BS23 4TQ, United Kingdom

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Wolverhampton, WV10 0QP, United Kingdom

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Related Publications (4)

• 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.

  PMID: 25038874 DERIVED

• 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.

  PMID: 24951609 DERIVED

• 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.

  PMID: 22116464 DERIVED

• 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.

  PMID: 20728210 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Trastuzumab; Fluorouracil; Cisplatin; Capecitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2009
• First Posted: December 31, 2009
• Study Start: September 1, 2005
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: November 5, 2014
• Results First Posted: November 5, 2014

Record last verified: 2014-10

Locations

IT (6); ZA (3); TW (3); IN (4); BR (4); PE (3); FI (1); PA (1); DE (5); CO (2); PT (9); JP (16); GB (8); GU (1); ES (7); DK (2); BE (1); FR (8); ME (5); RU (15); AU (6); KR (11); TU (5); CN (16)