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 (JACOB)

December 3, 2020 updated by: Hoffmann-La Roche

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

780

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane Womens Hosp; Division of Oncology
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre; Oncology
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health; Cancer Clinical Trial Centre
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital; Medical Oncology
  • Austria
      • Salzburg, Austria, 5020
        • Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
      • Zams, Austria, 6511
        • Krankenhaus St. Vinzenz Der Barmherzigen Schwestern Zams; Abt. Für Innere Medizin
  • Belgium
      • Bruxelles, Belgium, 1200
        • Cliniques Universitaires St-Luc
  • Brazil
    • RJ
      • Rio De Janeiro, RJ, Brazil, 22290-160
        • Clinicas Oncologicas Integradas - COI
    • RS
      • Porto Alegre, RS, Brazil, 91350-200
        • Hospital Nossa Senhora da Conceição
      • Porto Alegre, RS, Brazil
        • Hospital das Clinicas - UFRGS
    • SC
      • Florianopolis, SC, Brazil, 88034-000
        • Centro de Pesquisas Oncológicas - CEPON
    • SP
      • Sao Paulo, SP, Brazil, 01308-050
        • Hospital Sirio Libanes; Centro de Oncologia
      • Sao Paulo, SP, Brazil, 01509-010
        • Hospital A. C. Camargo; Oncologia
      • Sao Paulo, SP, Brazil, 01406100
        • Clinica de Oncologia Medica
      • Sao Paulo, SP, Brazil, 22793-080
        • Universidade Federal de Sao Paulo - UNIFESP*X
  • Bulgaria
      • Plovdiv, Bulgaria, 4004
        • Complex Oncological Center - Plovdiv, EOOD
      • Sofia, Bulgaria, 1301
        • MHAT Serdika
      • Varna, Bulgaria, 9010
        • SHATOD Dr. Marko Antonov Markov-Varna, EOOD; Department of Medicinall Onchotherapy and Palliative
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Hamilton Health Sciences - Juravinski Cancer Centre
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Centre
      • Sudbury, Ontario, Canada, P3E 5J1
        • Health Sciences North
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital; Oncology
      • Toronto, Ontario, Canada, M4C 3E7
        • Toronto East General Hospital; Haematology/Oncology
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Science Centre
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University; Glen Site; Oncology
  • China
      • Beijing, China, 100021
        • Cancer Hospital Chinese Academy of Medical Sciences.
      • Beijing, China, 100142
        • Beijing Cancer Hospital
      • Beijing, China, 100071
        • The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
      • Changchun, China, 130021
        • The First Hospital of Jilin University
      • Changchun, China, 132013
        • Jilin Cancer Hospital
      • Changzhou, China, 213003
        • Changzhou First People's Hospital
      • ChongQing, China, 400042
        • Third Affiliated Hospital of Third Military Medical University
      • Fuzhou, China, 110016
        • Fuzhou General Hospital, PLA Nanjing Military Area Command
      • Guangzhou, China, 510060
        • Sun Yet-sen University Cancer Center
      • Hangzhou, China, 310016
        • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
      • Harbin, China, 150081
        • Harbin Medical University Cancer Hospital
      • Nanchang, China, 330006
        • The 1st Affiliated Hospital of Nanchang Unversity
      • Nanjing City, China, 210002
        • The 81st Hospital of P.L.A.
      • Nantong, China, 226001
        • Affiliated Hospital of Nantong University
      • Shanghai, China, 200032
        • Zhongshan Hospital Fudan University
      • Shanghai, China, 200120
        • Fudan University Shanghai Cancer Center
      • Shenyang, China, 110016
        • General Hospital of Shenyang Military Command of PLA
      • Shijiazhuang, China, 050035
        • Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)
      • Xi'an, China, 710032
        • The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)
      • Xuzhou, China, 221000
        • The Affiliated Hospital of Xuzhou Medical College
      • Zhengzhou, China, 450008
        • Henan Cancer Hospital
      • Zhengzhou, China, 450052
        • The First Affiliated hospital of Zhengzhou University
  • Croatia
      • Zagreb, Croatia, 10000
        • Clinical Hospital Centre Zagreb
      • Zagreb, Croatia, 10000
        • Clinical Hospital Sisters of Mercy
  • El Salvador
      • Salvador, El Salvador, 01101
        • Hospital Oncologia; Oncology
  • Finland
      • Helsinki, Finland, 00180
        • Docrates Cance Center
      • Turku, Finland, 20520
        • Turku Uni Central Hospital; Oncology Clinics
  • Germany
      • Berlin, Germany, 10117
        • Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
      • Essen, Germany, 45122
        • Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
      • Essen, Germany, 45136
        • Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie
      • Esslingen, Germany, 73730
        • Klinik Esslingen; Klinik für Allgemeine Innere Medizin, Onkologie/Haematologie
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf; Hubertus Wald Tumorzentrum
      • Leipzig, Germany, 04103
        • Universitaetsklinikum Leipzig, Universitaeres Krebszentrum Leipzig (UCCL)
      • Ludwigsburg, Germany, 71640
        • Klinikum Ludwigsburg; Studiensekretariat
      • Mainz, Germany, 55131
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz; II. Medizinische Klinik
      • Mannheim, Germany, 68167
        • Universitätsklinikum Mannheim, Tagestherapiezentrum, Interdisziplinäres Tumorzentrum
      • Marburg, Germany, 35043
        • Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm; Zentrum für Innere Medizin Klinik für Innere Medizin I
  • Guatemala
      • Guatemala, Guatemala, 01-010
        • Medical Solution; Hematology
  • Hungary
      • Budapest, Hungary, 1122
        • Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly
      • Budapest, Hungary, 1083
        • Semmelweis Egyetem Onkologiai Központ
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika
      • Miskolc, Hungary, 3526
        • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz;Sugarterapias Klinikai Onkologiai Intez
      • Szeged, Hungary, 6720
        • Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
        • Seconda Universita' Degli Studi; Divsione Di Oncologia Medica
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
        • Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
      • Reggio Emilia, Emilia-Romagna, Italy, 42100
        • AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia
    • Friuli-Venezia Giulia
      • Udine, Friuli-Venezia Giulia, Italy, 33100
        • Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia
    • Lazio
      • Roma, Lazio, Italy, 00168
        • Policlinico Universitario Agostino Gemelli
    • Lombardia
      • Bergamo, Lombardia, Italy, 24127
        • Asst Papa Giovanni XXIII; Oncologia Medica
      • Milano, Lombardia, Italy, 20141
        • Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
      • Milano, Lombardia, Italy, 20132
        • IRCCS Ospedale San Raffaele
    • Marche
      • Ancona, Marche, Italy, 60121
        • Ospedali Riuniti Di Ancona; Oncology
    • Puglia
      • San Giovanni Rotondo, Puglia, Italy, 71013
        • Ospedale Casa Sollievo Della Sofferenza IRCCS
    • Toscana
      • Pisa, Toscana, Italy, 56100
        • Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2
      • Prato, Toscana, Italy, 59100
        • Ospedale Misericordia E Dolce; Oncologia Medica
  • Japan
      • Aichi, Japan, 464-8681
        • Aichi Cancer Center Hospital; Clinical Oncology
      • Aichi, Japan, 466-8560
        • Nagoya university Hospital; Gastroenterological Surgery 2
      • Chiba, Japan, 277-8577
        • National Cancer Center Hospital East; Gastroenterology
      • Ehime, Japan, 791-0280
        • National Hospital Organization Shikoku Cancer Center; Gastroenterology
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital; Surgery and Science
      • Gifu, Japan, 501-1194
        • Gifu University Hospital; Digestive Surgery
      • Hiroshima, Japan, 730-8518
        • Hiroshima City Hiroshima Citizens Hospital; Surgery
      • Hyogo, Japan, 650-0047
        • Kobe city Medical center General Hospital; Medical Oncology
      • Kanagawa, Japan, 216-8511
        • St.Marianna University School of Medicine hospital; Medical Oncology
      • Kanagawa, Japan, 241-8515
        • Kanagawa Cancer Center; Gastrointestinal Surgery
      • Osaka, Japan, 541-8567
        • Osaka International Cancer Institute;; Medical oncology and Gastrointestinal oncology
      • Osaka, Japan, 558-8558
        • Osaka General Medical Center; Gastroenterological Surgery
      • Saitama, Japan, 362-0806
        • Saitama Cancer Center; Gastroenterology
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital; Gastrointestinal Oncology
      • Toyama, Japan, 930-0194
        • Toyama University Hospital;Gastroenterology and Hematology
  • Kazakhstan
      • Almaty, Kazakhstan, 050022
        • Kazakh Scientific Research Institution Of Oncology and Radiology; Chemotherapy department
  • Korea, Republic of
      • Daegu, Korea, Republic of, 41404
        • Kyungpook National University Medical Center
      • Seoul, Korea, Republic of, 03080
        • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center; Medical Oncology
      • Seoul, Korea, Republic of, 06591
        • Seoul St Mary's Hospital
      • Seoul, Korea, Republic of, (0)6351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 03722
        • Yonsei Medical Center; Dept. of Medicine , Division of Hemato-Oncology
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • University Malaya Medical Centre; Clinical Oncology Unit,
      • Kuala Lumpur, Malaysia, 50586
        • Hospital Kuala Lumpur; Jabatan Radioterapi dan Onkologi
      • Sabah, Malaysia, 88996
        • Hospital Wanita dan Kanak-Kanak Sabah
    • Kelantan
      • Kubang Kerian, Kelantan, Malaysia, 16150
        • Hospital Universiti Sains Malaysia [Neurology]
  • Mexico
      • Mexico City, Mexico, 14000
        • Inst. Nacional de Cancerologia; Investigacion Clinica
      • Oaxaca, Mexico, 68000
        • Oaxaca Site Management Organization
    • Mexico CITY (federal District)
      • Mexico City, Mexico CITY (federal District), Mexico, 06760
        • Hospital Angeles Metropolitano; Room 220
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Academisch Medisch Centrum Universiteit Amsterdam
  • North Macedonia
      • Bitola, North Macedonia, 7000
        • Clinical Hospital; Oncology Department
      • Skopje, North Macedonia, 1000
        • University Clinic For Radiotherapy and Oncology
  • Panama
      • Panama, Panama
        • Medical Research Centre
  • Peru
      • Arequipa, Peru, 04001
        • Centro Medico Monte Carmelo
      • Callao, Peru, 02
        • Hospital Sabogal; Oncology
      • Jesus Maria, Peru, Lima 11
        • Hosp Nacion Edgardo Rebagliati; Oncologia Medica
      • Lima, Peru, Lima 41
        • Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional
      • Lima, Peru, Lima 41
        • Clinica San Borja
  • Poland
      • Bialystok, Poland, 15-027
        • Bialostockie Ctr Onkologii; Oddzial Chemioterapii Dziennej
      • Brzozów, Poland, 36-200
        • Szpital Specjalistyczny Podkarpacki Ośrodek Onkologiczny
      • Bydgoszcz, Poland, 85-796
        • Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
      • Kraków, Poland, 30-688
        • Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
      • Opole, Poland, 45-060
        • SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego
      • Poznan, Poland, 61-485
        • NZOZ Centrum Medyczne HCP Sp. z o.o.
      • Rybnik, Poland, 44-200
        • Wojewódzki Szpital Specjalistyczny Nr 3
      • Warszawa, Poland, 02-781
        • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Gastroenterologii Onkologicznej
  • Romania
      • Cluj-Napoca, Romania, 400015
        • Cardiomed Medical Center
      • Craiova, Romania, 200347
        • Oncology Center Sf. Nectarie
      • Iasi, Romania, 700106
        • Euroclinic Center of Oncology SRL
  • Russian Federation
      • Kazan, Russian Federation, 420029
        • Clinical Oncology Dispensary of Ministry of Health of Tatarstan
      • Omsk, Russian Federation, 644013
        • Clinical Oncology Dispensary; Chemotherapy
      • Ryazan, Russian Federation, 390011
        • SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF
      • Samara, Russian Federation, 443031
        • SBI of Healthcare Samara Regional Clinical Oncology Dispensary
  • Spain
      • Barcelona, Spain, 08003
        • Hospital del Mar; Servicio de Oncologia
      • Barcelona, Spain, 08035
        • Hospital Univ Vall d'Hebron; Servicio de Oncologia
      • Barcelona, Spain, 08907
        • Hospital Duran i Reynals; Oncologia
      • Barcelona, Spain, 08041
        • Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal; Servicio de Oncologia
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre; Servicio de Oncologia
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche; Servicio de Oncologia
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
    • Cordoba
      • Córdoba, Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia; Servicio de Oncologia
  • Switzerland
      • Lausanne, Switzerland, 1011
        • CHUV; Departement d'Oncologie
      • Luzern, Switzerland, 6004
        • Luzerner Kantonsspital; Medizinische Onkologie
  • Taiwan
      • Taichung, Taiwan, 407
        • Taichung Veterans General Hospital; Dept of Surgery
      • Tainan, Taiwan, 00704
        • National Cheng Kung University Hospital; Oncology
      • Taipei, Taiwan, 100
        • National Taiwan Uni Hospital; Dept of Oncology
      • Taipei City, Taiwan, 112
        • Taipei Veterans General Hospital
      • Taoyuan, Taiwan, 333
        • Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
  • Thailand
      • Bangkok, Thailand, 10700
        • Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
      • Bangkok, Thailand, 10400
        • Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
      • Bangkok, Thailand, 10400
        • Rajavithi Hospital; Division of Medical Oncology
      • Khonkaen, Thailand, 40000
        • Khonkaen Hospital
      • Songkhla, Thailand, 90110
        • Songklanagarind Hospital; Department of Oncology
  • Turkey
      • Ankara, Turkey, 06590
        • Ankara Uni School of Medicine; Medical Oncology
      • Antalya, Turkey, 07070
        • Akdeniz University Medical Faculty; Medical Oncology Department
      • Edirne, Turkey, 22770
        • Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
      • Erzurum, Turkey, 25240
        • Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department
      • Istanbul, Turkey, 34300
        • Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
      • Konya, Turkey, 42080
        • TC Necmettin Erbakan University Meram Medical Faculty Hospital
      • Malatya, Turkey, 44280
        • Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
  • United States
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists - SCRI; Pharmacy
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University Of Chicago Medical Center; Section Of Hematology/Oncology
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Indiana University Health; Goshen Center for Cancer Care
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada - Eastern Avenue
    • New York
      • Albany, New York, United States, 12206
        • New York Oncology Hematology, P.C.
      • Fresh Meadows, New York, United States, 11366
        • Queens Medical Associates
      • New York, New York, United States, 10065
        • Weill Medical College of Cornell University; Division of Hematology & Medical Oncology
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Oncology Hematology Care
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina; Hollings Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology PLLC - Nashville (20th Ave)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Pertuzumab + Trastuzumab + Chemotherapy
Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
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.
Drug: 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.
Other Names:
  • Xeloda
Drug: Cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
Drug: Pertuzumab
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Other Names:
  • Perjeta
  • RO4368451
Drug: 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.
Other Names:
  • Herceptin
  • RO0452317
PLACEBO_COMPARATOR: Placebo + Trastuzumab + Chemotherapy
Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
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.
Drug: 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.
Other Names:
  • Xeloda
Drug: Cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
Drug: 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.
Other Names:
  • Herceptin
  • RO0452317
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 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)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Time Frame: 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)
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)
Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
Time Frame: 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)
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)
Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
Time Frame: 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)
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)
Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria
Time Frame: 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)
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)
Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria
Time Frame: 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)
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)
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
Time Frame: From Baseline until end of post-treatment follow-up (up to 70 months)
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)
Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD)
Time Frame: From Baseline until end of post-treatment follow-up (up to 70 months)
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)
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
Time Frame: 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)
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)
Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score
Time Frame: 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)
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)
Maximum Serum Concentration (Cmax) of Pertuzumab
Time Frame: 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)
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)
Cmax of Trastuzumab
Time Frame: 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)
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)
Minimum Serum Concentration (Cmin) of Pertuzumab
Time Frame: Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)
Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)
Cmin of Trastuzumab
Time Frame: Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)
Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 10, 2013

Primary Completion (ACTUAL)

December 9, 2016

Study Completion (ACTUAL)

December 31, 2019

Study Registration Dates

First Submitted

January 21, 2013

First Submitted That Met QC Criteria

January 21, 2013

First Posted (ESTIMATE)

January 24, 2013

Study Record Updates

Last Update Posted (ACTUAL)

December 30, 2020

Last Update Submitted That Met QC Criteria

December 3, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BO25114
  • 2012-003554-83 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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