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)

• ClinicalTrials.gov Identifier: NCT01774786
• Recruitment Status: Completed
• First Posted: January 24, 2013
• Results First Posted: February 14, 2018
• Last Update Posted: December 30, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Gastric Cancer	Drug: 5-Fluorouracil; Drug: Capecitabine; Drug: Cisplatin; Drug: Pertuzumab; Drug: Placebo; Drug: Trastuzumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 780 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 10, 2013
• Actual Primary Completion Date: December 9, 2016
• Actual Study Completion Date: December 31, 2019

Arms and Interventions

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 Name: 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 Name: Xeloda; Drug: Cisplatin; Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.; 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.; 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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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).
9. 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).
10. 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) ]
11. 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) ]
12. 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) ]
13. 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) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

Florida Cancer Specialists - SCRI; Pharmacy

Fort Myers, Florida, United States, 33901

United States, Illinois

University Of Chicago Medical Center; Section Of Hematology/Oncology

Chicago, Illinois, United States, 60637

United States, Indiana

Indiana University Health; Goshen Center for Cancer Care

Goshen, Indiana, United States, 46526

United States, Nevada

Comprehensive Cancer Centers of Nevada - Eastern Avenue

Las Vegas, Nevada, United States, 89169

United States, New York

New York Oncology Hematology, P.C.

Albany, New York, United States, 12206

Queens Medical Associates

Fresh Meadows, New York, United States, 11366

Weill Medical College of Cornell University; Division of Hematology & Medical Oncology

New York, New York, United States, 10065

United States, Ohio

Oncology Hematology Care

Cincinnati, Ohio, United States, 45219

United States, South Carolina

Medical University of South Carolina; Hollings Cancer Center

Charleston, South Carolina, United States, 29425

United States, Tennessee

Tennessee Oncology PLLC - Nashville (20th Ave)

Nashville, Tennessee, United States, 37203

Australia, Queensland

Royal Brisbane Womens Hosp; Division of Oncology

Herston, Queensland, Australia, 4029

Australia, Victoria

Monash Medical Centre; Oncology

Clayton, Victoria, Australia, 3168

Austin Health; Cancer Clinical Trial Centre

Heidelberg, Victoria, Australia, 3084

Australia, Western Australia

Sir Charles Gairdner Hospital; Medical Oncology

Perth, Western Australia, Australia, 6009

Austria

Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.

Salzburg, Austria, 5020

Krankenhaus St. Vinzenz Der Barmherzigen Schwestern Zams; Abt. Für Innere Medizin

Zams, Austria, 6511

Belgium

Cliniques Universitaires St-Luc

Bruxelles, Belgium, 1200

Brazil

Clinicas Oncologicas Integradas - COI

Rio De Janeiro, RJ, Brazil, 22290-160

Hospital Nossa Senhora da Conceicao

Porto Alegre, RS, Brazil, 91350-200

Hospital das Clinicas - UFRGS

Porto Alegre, RS, Brazil

Centro de Pesquisas Oncologicas - CEPON

Florianopolis, SC, Brazil, 88034-000

Hospital Sirio Libanes; Centro de Oncologia

Sao Paulo, SP, Brazil, 01308-050

Clinica de Oncologia Medica

Sao Paulo, SP, Brazil, 01406100

Hospital A. C. Camargo; Oncologia

Sao Paulo, SP, Brazil, 01509-010

Universidade Federal de Sao Paulo - UNIFESP*X

Sao Paulo, SP, Brazil, 22793-080

Bulgaria

Complex Oncological Center - Plovdiv, EOOD

Plovdiv, Bulgaria, 4004

MHAT Serdika

Sofia, Bulgaria, 1301

SHATOD Dr. Marko Antonov Markov-Varna, EOOD; Department of Medicinall Onchotherapy and Palliative

Varna, Bulgaria, 9010

Canada, Ontario

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, Canada, L8V 5C2

London Regional Cancer Centre

London, Ontario, Canada, N6A 4L6

Health Sciences North

Sudbury, Ontario, Canada, P3E 5J1

Toronto East General Hospital; Haematology/Oncology

Toronto, Ontario, Canada, M4C 3E7

Sunnybrook Health Science Centre

Toronto, Ontario, Canada, M4N 3M5

Mount Sinai Hospital; Oncology

Toronto, Ontario, Canada, M5G 1X5

Canada, Quebec

McGill University; Glen Site; Oncology

Montreal, Quebec, Canada, H4A 3J1

China

Cancer Hospital Chinese Academy of Medical Sciences.

Beijing, China, 100021

The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)

Beijing, China, 100071

Beijing Cancer Hospital

Beijing, China, 100142

the First Hospital of Jilin University

Changchun, China, 130021

Jilin Cancer Hospital

Changchun, China, 132013

Changzhou First People's Hospital

Changzhou, China, 213003

Third Affiliated Hospital of Third Military Medical University

ChongQing, China, 400042

Fuzhou General Hospital, PLA Nanjing Military Area Command

Fuzhou, China, 110016

Sun Yet-sen University Cancer Center

Guangzhou, China, 510060

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Hangzhou, China, 310016

Harbin Medical University Cancer Hospital

Harbin, China, 150081

The 1st Affiliated Hospital of Nanchang Unversity

Nanchang, China, 330006

The 81st Hospital of P.L.A.

Nanjing City, China, 210002

Affiliated Hospital of Nantong University

Nantong, China, 226001

Zhongshan Hospital Fudan University

Shanghai, China, 200032

Fudan University Shanghai Cancer Center

Shanghai, China, 200120

General Hospital of Shenyang Military Command of PLA

Shenyang, China, 110016

Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)

Shijiazhuang, China, 050035

The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)

Xi'an, China, 710032

The Affiliated Hospital of Xuzhou Medical College

Xuzhou, China, 221000

Henan Cancer Hospital

Zhengzhou, China, 450008

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China, 450052

Croatia

Clinical Hospital Centre Zagreb

Zagreb, Croatia, 10000

Clinical Hospital Sisters of Mercy

Zagreb, Croatia, 10000

El Salvador

Hospital Oncologia; Oncology

Salvador, El Salvador, 01101

Finland

Docrates Cance Center

Helsinki, Finland, 00180

Turku Uni Central Hospital; Oncology Clinics

Turku, Finland, 20520

Germany

Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.

Berlin, Germany, 10117

Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung

Essen, Germany, 45122

Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie

Essen, Germany, 45136

Klinik Esslingen; Klinik für Allgemeine Innere Medizin, Onkologie/Haematologie

Esslingen, Germany, 73730

Universitätsklinikum Hamburg-Eppendorf; Hubertus Wald Tumorzentrum

Hamburg, Germany, 20246

Universitaetsklinikum Leipzig, Universitaeres Krebszentrum Leipzig (UCCL)

Leipzig, Germany, 04103

Klinikum Ludwigsburg; Studiensekretariat

Ludwigsburg, Germany, 71640

Universitätsmedizin der Johannes Gutenberg-Universität Mainz; II. Medizinische Klinik

Mainz, Germany, 55131

Universitätsklinikum Mannheim, Tagestherapiezentrum, Interdisziplinäres Tumorzentrum

Mannheim, Germany, 68167

Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie

Marburg, Germany, 35043

Universitätsklinikum Ulm; Zentrum für Innere Medizin Klinik für Innere Medizin I

Ulm, Germany, 89081

Guatemala

Medical Solution; Hematology

Guatemala, Guatemala, 01-010

Hungary

Semmelweis Egyetem Onkologiai Központ

Budapest, Hungary, 1083

Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly

Budapest, Hungary, 1122

Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika

Debrecen, Hungary, 4032

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz;Sugarterapias Klinikai Onkologiai Intez

Miskolc, Hungary, 3526

Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika

Szeged, Hungary, 6720

Italy

Seconda Universita' Degli Studi; Divsione Di Oncologia Medica

Napoli, Campania, Italy, 80131

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica

Bologna, Emilia-Romagna, Italy, 40138

AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia

Reggio Emilia, Emilia-Romagna, Italy, 42100

Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia

Udine, Friuli-Venezia Giulia, Italy, 33100

Policlinico Universitario Agostino Gemelli

Roma, Lazio, Italy, 00168

Asst Papa Giovanni XXIII; Oncologia Medica

Bergamo, Lombardia, Italy, 24127

Irccs Ospedale San Raffaele

Milano, Lombardia, Italy, 20132

Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica

Milano, Lombardia, Italy, 20141

Ospedali Riuniti Di Ancona; Oncology

Ancona, Marche, Italy, 60121

Ospedale Casa Sollievo Della Sofferenza IRCCS

San Giovanni Rotondo, Puglia, Italy, 71013

Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2

Pisa, Toscana, Italy, 56100

Ospedale Misericordia E Dolce; Oncologia Medica

Prato, Toscana, Italy, 59100

Japan

Aichi Cancer Center Hospital; Clinical Oncology

Aichi, Japan, 464-8681

Nagoya university Hospital; Gastroenterological Surgery 2

Aichi, Japan, 466-8560

National Cancer Center Hospital East; Gastroenterology

Chiba, Japan, 277-8577

National Hospital Organization Shikoku Cancer Center; Gastroenterology

Ehime, Japan, 791-0280

Kyushu University Hospital; Surgery and Science

Fukuoka, Japan, 812-8582

Gifu University Hospital; Digestive Surgery

Gifu, Japan, 501-1194

Hiroshima City Hiroshima Citizens Hospital; Surgery

Hiroshima, Japan, 730-8518

Kobe city Medical center General Hospital; Medical Oncology

Hyogo, Japan, 650-0047

St.Marianna University School of Medicine hospital; Medical Oncology

Kanagawa, Japan, 216-8511

Kanagawa Cancer Center; Gastrointestinal Surgery

Kanagawa, Japan, 241-8515

Osaka International Cancer Institute;; Medical oncology and Gastrointestinal oncology

Osaka, Japan, 541-8567

Osaka General Medical Center; Gastroenterological Surgery

Osaka, Japan, 558-8558

Saitama Cancer Center; Gastroenterology

Saitama, Japan, 362-0806

National Cancer Center Hospital; Gastrointestinal Oncology

Tokyo, Japan, 104-0045

Toyama University Hospital;Gastroenterology and Hematology

Toyama, Japan, 930-0194

Kazakhstan

Kazakh Scientific Research Institution Of Oncology and Radiology; Chemotherapy department

Almaty, Kazakhstan, 050022

Korea, Republic of

Kyungpook National University Medical Center

Daegu, Korea, Republic of, 41404

Samsung Medical Center

Seoul, Korea, Republic of, (0)6351

Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology

Seoul, Korea, Republic of, 03080

Yonsei Medical Center; Dept. of Medicine , Division of Hemato-Oncology

Seoul, Korea, Republic of, 03722

Asan Medical Center; Medical Oncology

Seoul, Korea, Republic of, 05505

Seoul St Mary's Hospital

Seoul, Korea, Republic of, 06591

Malaysia

Hospital Universiti Sains Malaysia [Neurology]

Kubang Kerian, Kelantan, Malaysia, 16150

Hospital Kuala Lumpur; Jabatan Radioterapi dan Onkologi

Kuala Lumpur, Malaysia, 50586

University Malaya Medical Centre; Clinical Oncology Unit,

Kuala Lumpur, Malaysia, 59100

Hospital Wanita dan Kanak-Kanak Sabah

Sabah, Malaysia, 88996

Mexico

Hospital Angeles Metropolitano; Room 220

Mexico City, Mexico CITY (federal District), Mexico, 06760

Inst. Nacional de Cancerologia; Investigacion Clinica

Mexico City, Mexico, 14000

Oaxaca Site Management Organization

Oaxaca, Mexico, 68000

Netherlands

Academisch Medisch Centrum Universiteit Amsterdam

Amsterdam, Netherlands, 1105 AZ

North Macedonia

Clinical Hospital; Oncology Department

Bitola, North Macedonia, 7000

University Clinic for Radiotherapy and Oncology

Skopje, North Macedonia, 1000

Panama

Medical Research Centre

Panama, Panama

Peru

Centro Medico Monte Carmelo

Arequipa, Peru, 04001

Hospital Sabogal; Oncology

Callao, Peru, 02

Hosp Nacion Edgardo Rebagliati; Oncologia Medica

Jesus Maria, Peru, Lima 11

Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional

Lima, Peru, Lima 41

Clinica San Borja

Lima, Peru, Lima 41

Poland

Bialostockie Ctr Onkologii; Oddzial Chemioterapii Dziennej

Bialystok, Poland, 15-027

Szpital Specjalistyczny Podkarpacki Ośrodek Onkologiczny

Brzozów, Poland, 36-200

Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii

Bydgoszcz, Poland, 85-796

Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii

Kraków, Poland, 30-688

SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego

Opole, Poland, 45-060

NZOZ Centrum Medyczne HCP Sp. z o.o.

Poznan, Poland, 61-485

Wojewódzki Szpital Specjalistyczny Nr 3

Rybnik, Poland, 44-200

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Gastroenterologii Onkologicznej

Warszawa, Poland, 02-781

Romania

Cardiomed Medical Center

Cluj-Napoca, Romania, 400015

Oncology Center Sf. Nectarie

Craiova, Romania, 200347

Euroclinic Center of Oncology SRL

Iasi, Romania, 700106

Russian Federation

Clinical Oncology Dispensary of Ministry of Health of Tatarstan

Kazan, Russian Federation, 420029

Clinical Oncology Dispensary; Chemotherapy

Omsk, Russian Federation, 644013

SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF

Ryazan, Russian Federation, 390011

SBI of Healthcare Samara Regional Clinical Oncology Dispensary

Samara, Russian Federation, 443031

Spain

Hospital General Universitario de Elche; Servicio de Oncologia

Elche, Alicante, Spain, 03203

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Badalona, Barcelona, Spain, 08916

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain, 14004

Hospital del Mar; Servicio de Oncologia

Barcelona, Spain, 08003

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Spain, 08035

Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia

Barcelona, Spain, 08041

Hospital Duran i Reynals; Oncologia

Barcelona, Spain, 08907

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, Spain, 28034

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, Spain, 28041

Switzerland

CHUV; Departement d'Oncologie

Lausanne, Switzerland, 1011

Luzerner Kantonsspital; Medizinische Onkologie

Luzern, Switzerland, 6004

Taiwan

Taichung Veterans General Hospital; Dept of Surgery

Taichung, Taiwan, 407

National Cheng Kung University Hospital; Oncology

Tainan, Taiwan, 00704

Taipei Veterans General Hospital

Taipei City, Taiwan, 112

National Taiwan Uni Hospital; Dept of Oncology

Taipei, Taiwan, 100

Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology

Taoyuan, Taiwan, 333

Thailand

Rajavithi Hospital; Division of Medical Oncology

Bangkok, Thailand, 10400

Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc

Bangkok, Thailand, 10400

Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology

Bangkok, Thailand, 10700

Khonkaen Hospital

Khonkaen, Thailand, 40000

Songklanagarind Hospital; Department of Oncology

Songkhla, Thailand, 90110

Turkey

Ankara Uni School of Medicine; Medical Oncology

Ankara, Turkey, 06590

Akdeniz University Medical Faculty; Medical Oncology Department

Antalya, Turkey, 07070

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

Edirne, Turkey, 22770

Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department

Erzurum, Turkey, 25240

Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology

Istanbul, Turkey, 34300

TC Necmettin Erbakan University Meram Medical Faculty Hospital

Konya, Turkey, 42080

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, Turkey, 44280

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Siddiqui A, Heeson S, Kiermaier A, Macharia H, Restuccia E, Kang YK. Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial. Gastric Cancer. 2023 Jan;26(1):123-131. doi: 10.1007/s10120-022-01335-4. Epub 2022 Sep 6.

Liu T, Qin Y, Li J, Xu R, Xu J, Yang S, Qin S, Bai Y, Wu C, Mao Y, Wu H, Ge Y, Shen L. Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial. Cancer Commun (Lond). 2019 Jun 24;39(1):38. doi: 10.1186/s40880-019-0384-6.

Kirschbrown WP, Wang B, Nijem I, Ohtsu A, Hoff PM, Shah MA, Shen L, Kang YK, Alsina M, Girish S, Garg A. Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer. Cancer Chemother Pharmacol. 2019 Sep;84(3):539-550. doi: 10.1007/s00280-019-03871-w. Epub 2019 Jun 10.

Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. doi: 10.1016/S1470-2045(18)30481-9. Epub 2018 Sep 11.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01774786
• Other Study ID Numbers: BO25114; 2012-003554-83 ( EudraCT Number )
• First Posted: January 24, 2013
• Results First Posted: February 14, 2018
• Last Update Posted: December 30, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Stomach Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Capecitabine; Fluorouracil; Trastuzumab; Pertuzumab; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Immunological