A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer

Gastric Cancer Clinical Trial

— JACOB  

Official title:

A Double-Blind, Placebo-Controlled, Randomized, Multicenter Phase III Study Evaluating the Efficacy and Safety of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Metastatic Gastroesophageal Junction and Gastric Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01774786
• Other study ID #: BO25114
• Secondary ID: 2012-003554-83
• Status: Completed
• Phase: Phase 3
• Start date: June 10, 2013
• Est. completion date: December 31, 2019

Study information

• Verified date: December 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab, fluoropyrimidine and cisplatin as first-line treatment in participants with HER2-positive metastatic gastroesophageal junction (GEJ) or gastric cancer (GC). Participants will be randomized to receive pertuzumab 840 milligrams (mg) or placebo intravenously every 3 weeks (q3w) in combination with trastuzumab (initial dose of 8 milligrams per kilogram [mg/kg] intravenously [IV] followed by 6 mg/kg IV q3w) and cisplatin and fluoropyrimidine (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Participants will continue to receive pertuzumab or placebo and trastuzumab until disease progression occurrence of unacceptable toxicity or withdrawal from the study for another reason.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 780
• Est. completion date: December 31, 2019
• Est. primary completion date: December 9, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed metastatic adenocarcinoma of the stomach or GEJ
• Measurable or evaluable non-measurable disease as assessed by the investigator according to RECIST v1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy greater than equal to (>/=) 3 months

Exclusion Criteria:

• Previous cytotoxic chemotherapy for advanced (metastatic) disease
• Evidence of disease progression documented within 6 months after completion of prior neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ adenocarcinoma
• Previous treatment with any HER2-directed therapy, at any time, for any duration
• Previous exposure to any investigational treatment within 30 days before the first dose of study treatment
• Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks if given as palliation to bone metastases, if recovered from all toxicities)
• History or evidence of brain metastases
• Clinically significant active gastrointestinal (GI) bleeding (Grade >/=2 according to National Cancer Institute [NIC]-Common Terminology Criteria for Adverse Events Version 4.0 [CTCAEv.4.0])
• Residual toxicity resulting from previous therapy (for example, hematologic, cardiovascular, or neurologic toxicity that is Grade >/=2). Alopecia is permitted
• Other malignancy (in addition to gastric cancer [GC]) within 5 years before enrollment, except for carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin that has been previously treated with curative intent
• Inadequate hematologic, renal or liver function
• Pregnant or lactating women
• History of congestive heart failure of any New York Heart Association (NYHA) criteria
• Angina pectoris requiring treatment
• Myocardial infarction within the past 6 months before the first dose of study drug
• Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia
• History or evidence of poorly controlled hypertension
• Baseline left ventricular ejection fraction (LVEF) value less than (<) 55 percent (%)
• Any significant uncontrolled intercurrent systemic illness
• Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• 5-Fluorouracil
Participants will receive 5-fluorouracil 800 milligrams per meter square (mg/m^2)/24 hour IV infusion for 120 hours (Days 1-5) q3w for 6 cycles.
• Capecitabine
Participants will receive capecitabine 1000 mg/m^2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) q3w for 6 cycles.
• Cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
• Pertuzumab
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
• Placebo
Participants will receive placebo (matched to pertuzumab) IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
• Trastuzumab
Participants will receive 8 mg/kg IV initial dose on Day 1, followed by 6 mg/kg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Locations

Country	Name	City	State
Australia	Monash Medical Centre; Oncology	Clayton	Victoria
Australia	Austin Health; Cancer Clinical Trial Centre	Heidelberg	Victoria
Australia	Royal Brisbane Womens Hosp; Division of Oncology	Herston	Queensland
Australia	Sir Charles Gairdner Hospital; Medical Oncology	Perth	Western Australia
Austria	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg
Austria	Krankenhaus St. Vinzenz Der Barmherzigen Schwestern Zams; Abt. Für Innere Medizin	Zams
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Brazil	Centro de Pesquisas Oncologicas - CEPON	Florianopolis	SC
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Clinicas Oncologicas Integradas - COI	Rio De Janeiro	RJ
Brazil	Clinica de Oncologia Medica	Sao Paulo	SP
Brazil	Hospital A. C. Camargo; Oncologia	Sao Paulo	SP
Brazil	Hospital Sirio Libanes; Centro de Oncologia	Sao Paulo	SP
Brazil	Universidade Federal de Sao Paulo - UNIFESP*X	Sao Paulo	SP
Bulgaria	Complex Oncological Center - Plovdiv, EOOD	Plovdiv
Bulgaria	MHAT Serdika	Sofia
Bulgaria	SHATOD Dr. Marko Antonov Markov-Varna, EOOD; Department of Medicinall Onchotherapy and Palliative	Varna
Canada	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Regional Cancer Centre	London	Ontario
Canada	McGill University; Glen Site; Oncology	Montreal	Quebec
Canada	Health Sciences North	Sudbury	Ontario
Canada	Mount Sinai Hospital; Oncology	Toronto	Ontario
Canada	Sunnybrook Health Science Centre	Toronto	Ontario
Canada	Toronto East General Hospital; Haematology/Oncology	Toronto	Ontario
China	Beijing Cancer Hospital	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences.	Beijing
China	The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)	Beijing
China	Jilin Cancer Hospital	Changchun
China	the First Hospital of Jilin University	Changchun
China	Changzhou First People's Hospital	Changzhou
China	Third Affiliated Hospital of Third Military Medical University	ChongQing
China	Fuzhou General Hospital, PLA Nanjing Military Area Command	Fuzhou
China	Sun Yet-sen University Cancer Center	Guangzhou
China	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	The 1st Affiliated Hospital of Nanchang Unversity	Nanchang
China	The 81st Hospital of P.L.A.	Nanjing City
China	Affiliated Hospital of Nantong University	Nantong
China	Fudan University Shanghai Cancer Center	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	General Hospital of Shenyang Military Command of PLA	Shenyang
China	Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)	Shijiazhuang
China	The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)	Xi'an
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou
China	Henan Cancer Hospital	Zhengzhou
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Croatia	Clinical Hospital Sisters of Mercy	Zagreb
El Salvador	Hospital Oncologia; Oncology	Salvador
Finland	Docrates Cance Center	Helsinki
Finland	Turku Uni Central Hospital; Oncology Clinics	Turku
Germany	Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.	Berlin
Germany	Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie	Essen
Germany	Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung	Essen
Germany	Klinik Esslingen; Klinik für Allgemeine Innere Medizin, Onkologie/Haematologie	Esslingen
Germany	Universitätsklinikum Hamburg-Eppendorf; Hubertus Wald Tumorzentrum	Hamburg
Germany	Universitaetsklinikum Leipzig, Universitaeres Krebszentrum Leipzig (UCCL)	Leipzig
Germany	Klinikum Ludwigsburg; Studiensekretariat	Ludwigsburg
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz; II. Medizinische Klinik	Mainz
Germany	Universitätsklinikum Mannheim, Tagestherapiezentrum, Interdisziplinäres Tumorzentrum	Mannheim
Germany	Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie	Marburg
Germany	Universitätsklinikum Ulm; Zentrum für Innere Medizin Klinik für Innere Medizin I	Ulm
Guatemala	Medical Solution; Hematology	Guatemala
Hungary	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest
Hungary	Semmelweis Egyetem Onkologiai Központ	Budapest
Hungary	Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika	Debrecen
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz;Sugarterapias Klinikai Onkologiai Intez	Miskolc
Hungary	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged
Italy	Ospedali Riuniti Di Ancona; Oncology	Ancona	Marche
Italy	Asst Papa Giovanni XXIII; Oncologia Medica	Bergamo	Lombardia
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele	Milano	Lombardia
Italy	Seconda Universita' Degli Studi; Divsione Di Oncologia Medica	Napoli	Campania
Italy	Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2	Pisa	Toscana
Italy	Ospedale Misericordia E Dolce; Oncologia Medica	Prato	Toscana
Italy	AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia	Reggio Emilia	Emilia-Romagna
Italy	Policlinico Universitario Agostino Gemelli	Roma	Lazio
Italy	Ospedale Casa Sollievo Della Sofferenza IRCCS	San Giovanni Rotondo	Puglia
Italy	Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia	Udine	Friuli-Venezia Giulia
Japan	Aichi Cancer Center Hospital; Clinical Oncology	Aichi
Japan	Nagoya university Hospital; Gastroenterological Surgery 2	Aichi
Japan	National Cancer Center Hospital East; Gastroenterology	Chiba
Japan	National Hospital Organization Shikoku Cancer Center; Gastroenterology	Ehime
Japan	Kyushu University Hospital; Surgery and Science	Fukuoka
Japan	Gifu University Hospital; Digestive Surgery	Gifu
Japan	Hiroshima City Hiroshima Citizens Hospital; Surgery	Hiroshima
Japan	Kobe city Medical center General Hospital; Medical Oncology	Hyogo
Japan	Kanagawa Cancer Center; Gastrointestinal Surgery	Kanagawa
Japan	St.Marianna University School of Medicine hospital; Medical Oncology	Kanagawa
Japan	Osaka General Medical Center; Gastroenterological Surgery	Osaka
Japan	Osaka International Cancer Institute;; Medical oncology and Gastrointestinal oncology	Osaka
Japan	Saitama Cancer Center; Gastroenterology	Saitama
Japan	National Cancer Center Hospital; Gastrointestinal Oncology	Tokyo
Japan	Toyama University Hospital;Gastroenterology and Hematology	Toyama
Kazakhstan	Kazakh Scientific Research Institution Of Oncology and Radiology; Chemotherapy department	Almaty
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	Asan Medical Center; Medical Oncology	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Yonsei Medical Center; Dept. of Medicine , Division of Hemato-Oncology	Seoul
Malaysia	Hospital Kuala Lumpur; Jabatan Radioterapi dan Onkologi	Kuala Lumpur
Malaysia	University Malaya Medical Centre; Clinical Oncology Unit,	Kuala Lumpur
Malaysia	Hospital Universiti Sains Malaysia [Neurology]	Kubang Kerian	Kelantan
Malaysia	Hospital Wanita dan Kanak-Kanak Sabah	Sabah
Mexico	Hospital Angeles Metropolitano; Room 220	Mexico City	Mexico CITY (federal District)
Mexico	Inst. Nacional de Cancerologia; Investigacion Clinica	Mexico City
Mexico	Oaxaca Site Management Organization	Oaxaca
Netherlands	Academisch Medisch Centrum Universiteit Amsterdam	Amsterdam
North Macedonia	Clinical Hospital; Oncology Department	Bitola
North Macedonia	University Clinic for Radiotherapy and Oncology	Skopje
Panama	Medical Research Centre	Panama
Peru	Centro Medico Monte Carmelo	Arequipa
Peru	Hospital Sabogal; Oncology	Callao
Peru	Hosp Nacion Edgardo Rebagliati; Oncologia Medica	Jesus Maria
Peru	Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional	Lima
Peru	Clinica San Borja	Lima
Poland	Bialostockie Ctr Onkologii; Oddzial Chemioterapii Dziennej	Bialystok
Poland	Szpital Specjalistyczny Podkarpacki Osrodek Onkologiczny	Brzozów
Poland	Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii	Bydgoszcz
Poland	Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Kliniki Onkologii	Kraków
Poland	SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego	Opole
Poland	NZOZ Centrum Medyczne HCP Sp. z o.o.	Poznan
Poland	Wojewódzki Szpital Specjalistyczny Nr 3	Rybnik
Poland	Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Gastroenterologii Onkologicznej	Warszawa
Romania	Cardiomed Medical Center	Cluj-Napoca
Romania	Oncology Center Sf. Nectarie	Craiova
Romania	Euroclinic Center of Oncology SRL	Iasi
Russian Federation	Clinical Oncology Dispensary of Ministry of Health of Tatarstan	Kazan
Russian Federation	Clinical Oncology Dispensary; Chemotherapy	Omsk
Russian Federation	SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF	Ryazan
Russian Federation	SBI of Healthcare Samara Regional Clinical Oncology Dispensary	Samara
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Hospital Duran i Reynals; Oncologia	Barcelona
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital General Universitario de Elche; Servicio de Oncologia	Elche	Alicante
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Switzerland	CHUV; Departement d'Oncologie	Lausanne
Switzerland	Luzerner Kantonsspital; Medizinische Onkologie	Luzern
Taiwan	Taichung Veterans General Hospital; Dept of Surgery	Taichung
Taiwan	National Cheng Kung University Hospital; Oncology	Tainan
Taiwan	National Taiwan Uni Hospital; Dept of Oncology	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Thailand	Rajavithi Hospital; Division of Medical Oncology	Bangkok
Thailand	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok
Thailand	Khonkaen Hospital	Khonkaen
Thailand	Songklanagarind Hospital; Department of Oncology	Songkhla
Turkey	Ankara Uni School of Medicine; Medical Oncology	Ankara
Turkey	Akdeniz University Medical Faculty; Medical Oncology Department	Antalya
Turkey	Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department	Edirne
Turkey	Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department	Erzurum
Turkey	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul
Turkey	TC Necmettin Erbakan University Meram Medical Faculty Hospital	Konya
Turkey	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Medical University of South Carolina; Hollings Cancer Center	Charleston	South Carolina
United States	University Of Chicago Medical Center; Section Of Hematology/Oncology	Chicago	Illinois
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Florida Cancer Specialists - SCRI; Pharmacy	Fort Myers	Florida
United States	Queens Medical Associates	Fresh Meadows	New York
United States	Indiana University Health; Goshen Center for Cancer Care	Goshen	Indiana
United States	Comprehensive Cancer Centers of Nevada - Eastern Avenue	Las Vegas	Nevada
United States	Tennessee Oncology PLLC - Nashville (20th Ave)	Nashville	Tennessee
United States	Weill Medical College of Cornell University; Division of Hematology & Medical Oncology	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Croatia,  El Salvador,  Finland,  Germany,  Guatemala,  Hungary,  Italy,  Japan,  Kazakhstan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  North Macedonia,  Panama,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall survival (OS) was defined as the time from randomization to death from any cause. For participants who were still alive on the date of clinical data cut-off for the OS analysis, the last date when the participant was known to be alive on, or prior to the clinical cut-off date, was used to determine the censoring date. Participants who did not have any post-baseline data (e.g., dosing records, imaging dates, visit dates) were censored at the date of randomization plus 1 day.	From Baseline until death from any cause (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.4 [0-42] months vs. 25.0 [0-41] months; Final Analysis: 46.1 [0-70] months vs. 44.4 [0-68] months)
Secondary	Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria	Progression-free survival (PFS) is defined as the time from randomization to the first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Tumor assessments with CT or MRI scans of the chest, abdomen, and pelvis were performed every 9 weeks. Participants without documented PD or death were censored at the tumor assessment date for which the participant was last known to be progression-free. Participants who did not have any post-baseline tumor assessment data were censored at the date of randomization plus 1 day. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 millimeters (mm) in the sum of diameters of target lesions; the appearance of one or more new lesions.	Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)
Secondary	Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria	The overall objective response rate was defined as the percentage of participants with partial response (PR) or complete response (CR) occurring on two consecutive occasions =4 weeks apart, as determined by the investigator using RECIST v1.1. Tumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis were performed every 9 weeks. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be greater than or equal to (=) 15 mm in short axis when assessed by CT scan.	Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)
Secondary	Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria	The overall objective response rate was defined as the percentage of participants with partial response (PR) or complete response (CR) occurring on two consecutive occasions =4 weeks apart, as determined by the investigator using RECIST v1.1. Tumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis were performed every 9 weeks. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be greater than or equal to (=) 15 mm in short axis when assessed by CT scan.	Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Final Analysis: 50.4 [0-70] months vs. 47.4 [0-66] months)
Secondary	Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria	Duration of objective response is defined as the time from first occurrence of documented objective response to documented disease progression, as determined by the investigator using RECIST v1.1, or death from any cause. Objective response: PR or CR occurring on 2 consecutive occasions =4 weeks apart. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions. Measurable disease defined as tumor lesions with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node, it must be =15 mm in short axis when assessed by CT scan.	Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)
Secondary	Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria	The clinical benefit rate was defined as best response of complete response (CR) or partial response (PR) or stable disease (SD) for 6 weeks or longer, as determined by the investigator using RECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum diameters while on study. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be >/=15 mm in short axis when assessed by CT scan. The clinical benefit rate was not updated at the final analysis.	Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)
Secondary	Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. The investigator graded all AEs for severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.	From Baseline until end of post-treatment follow-up (up to 70 months)
Secondary	Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD)	The number and percentage of participants with symptomatic left ventricular systolic dysfunction (LVSD) and asymptomatic LVSD events (defined as a left ventricular ejection fraction [LVEF] =10% decrease from baseline to an absolute value <50%) at any time during the study was summarized by treatment arm.	From Baseline until end of post-treatment follow-up (up to 70 months)
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score	The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).	Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)
Secondary	Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score	The EORTC 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. A positive value means an increase, while a negative values means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).	Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)
Secondary	Maximum Serum Concentration (Cmax) of Pertuzumab		Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)
Secondary	Cmax of Trastuzumab		Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)
Secondary	Minimum Serum Concentration (Cmin) of Pertuzumab		Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)
Secondary	Cmin of Trastuzumab		Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)