Neoadjuvant Study Using Trastuzumab or Trastuzumab With Pertuzumab in Gastric or Gastroesophageal Junction Adenocarcinoma

NCT02205047 | Completed Phase 2 DMC

• 3 other identifiers: EORTC-1203-GITCG2014-000722-38MO28922
• Study Type: interventional
• Target: 172
• Locations: 12 countries
• Sites: 42

Brief Summary

The purpose of this study is to find out whether either trastuzumab or the combination of trastuzumab and pertuzumab with standard chemotherapy shows more activity against gastro-oesophageal adenocarcinoma than standard chemotherapy given before and after surgery and it can be safely administered.

Conditions

Malignant Neoplasm of Stomach; Malignant Neoplasm of Cardio-esophageal Junction of Stomach; Epidermal Growth Factor Receptor (EGFR) Protein Overexpression

Keywords

Neoadjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• Near Complete Pathological Response Rate

  To increase the major pathological response rate (\< 10% vital tumor cells) to neoadjuvant treatment by integrating both trastuzumab and pertuzumab into perioperative chemotherapy for HER-2 positive, resectable gastric cancer.

  After 3 cycles (21 days) of neoadjuvant chemotherapy

Secondary Outcomes (7)

• Locoregional failure

  At the time of surgery and at 5 years

• R0 resection rate

  At the time of surgery

• Distant failure

  At the time of surgery and at 5 years

• Progression-free survival

  5 years after LPI

• Recurrence-free survival

  5 years after LPI

Study Arms (3)

Standard chemotherapy

ACTIVE COMPARATOR

Cisplatin/capecitabine or cisplatin/5-fluorouracil

Drug: Cisplatin; Drug: 5-fluorouracil or Capecitabine; Procedure: gastrectomy

Experimental arm 1

EXPERIMENTAL

Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab

Drug: Cisplatin; Drug: 5-fluorouracil or Capecitabine; Drug: Trastuzumab; Procedure: gastrectomy

Experimental arm 2

EXPERIMENTAL

cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab

Drug: Cisplatin; Drug: 5-fluorouracil or Capecitabine; Drug: Trastuzumab; Drug: Pertuzumab; Procedure: gastrectomy

Interventions

Cisplatin DRUG

Experimental arm 1; Experimental arm 2; Standard chemotherapy

5-fluorouracil or Capecitabine DRUG

Experimental arm 1; Experimental arm 2; Standard chemotherapy

Trastuzumab DRUG

Experimental arm 1; Experimental arm 2

Pertuzumab DRUG

Experimental arm 2

gastrectomy PROCEDURE

D2 gastrectomy

Experimental arm 1; Experimental arm 2; Standard chemotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically proven, gastric or gastroesophageal (GE)-junction adenocarcinoma (Siewert I-III)
• Patient medically fit for gastrectomy/oesophagogastrectomy as decided by the investigator
• Age ≥ 18 years
• WHO performance status 0 - 1
• HER-2 overexpression
• Amenable to gastrectomy/oesophagectomy
• The cardiac ejection fraction (LVEF), as determined by echocardiography, multiple gated acquisition scan (MUGA) or cardiac MRI should be at least 50 %
• Adequate organ function
• written informed consent
• For women who are not postmenopausal (\> 12 months of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 12 months after the last treatment dose
• For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for at least 12 months after the last dose of study treatment. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods for contraception.

You may not qualify if:

• Absence of distant metastases on CT scan of thorax and abdomen
• prior chemo- or antibody therapy
• history of significant cardiac disease
• current uncontrolled hypertension
• known hypersensitivity to the components of trastuzumab, pertuzumab, cisplatin, 5-follow-up or capecitabine
• known dihydropyrimidine dehydrogenase (DPD) deficiency
• ongoing or concomitant use of the antiviral drug sorivudine or its chemically related analogs, such as brivudine
• chronic treatment with high-dose intravenous corticosteroids
• previous malignancy within the last 5 years, with the exception of adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer, or other curatively treated cancer without impact on the patient's overall prognosis according to the judgment of the investigator.
• psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• pregnant or breast feeding

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (48)

University Hospital Gent

Ghent, Flanders, 9000, Belgium

Location

North Estonia Medical Centre

Tallinn, 13419, Estonia

Location

CHRU de Besancon - Hopital Jean Minjoz

Besançon, 25030, France

Location

CHRU de Lille - Hopital Huriez

Lille, 59037, France

Location

CHU de Bordeaux - Group Hospitalier Sud - Hopital Haut-Lévêque

Pessac, 33075, France

Location

CHU de Reims - Hôpital Robert Debré

Reims, 51092, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Universitaetsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Kliniken Essen-Mitte - Evang. Huyssens-Stiftung

Essen, 45136, Germany

Location

Universitaetsmedizin Goettingen - Georg-August Universitaet

Göttingen, 37075, Germany

Location

Asklepios Kliniken GmbH - Asklepios Klinik Barmbek

Hamburg, 22291, Germany

Location

SLK-Kliniken Heilbronn GmbH

Heilbronn, 74078, Germany

Location

Onkologische Unter-Ems (Leer-Papenburg-Emden)

Leer, 26789, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, Germany

Location

Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center

Mainz, 55101, Germany

Location

Ludwig-Maximilians-Universitaet München - Campus Grosshadern

München, 81377, Germany

Location

Technische Universität München - Klinikum Rechts der Isar

München, Germany

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliera Ordine Mauriziano di Torino

Torino, Italy

Location

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Academisch Medisch Centrum - UMC Universiteit van Amsterdam - site: VUMC

Amsterdam, 1081 HV, Netherlands

Location

Oslo University Hospital - Radiumhospitalet

Oslo, 0379, Norway

Location

Instituto Portugues de Oncologia de Lisboa Francisco Gentil

Lisbon, Portugal

Location

Instituto Portugues De Oncologia - Centro Do Porto

Porto, 4200-072, Portugal

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital

Seoul, 135-720, South Korea

Location

Hallym University Sacred Heart Hospital

Seoul, 14068, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Gangnam Severance Hospital

Seoul, South Korea

Location

Hallym University Sacred Heart Hospital

Seoul, South Korea

Location

Severance Hospital YUCM

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System (YUCM)

Seoul, South Korea

Location

The Catholic University of Korea-St. Vincent's Hospital

Suwon-Si Gyeonggi-do, 16247, South Korea

Location

Institut Catala d'Oncologia - ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

ICO Badalona (Institut Catala d'Oncologia) - Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Universitari Vall d'Hebron - Institut Oncologia

Barcelona, 08035, Spain

Location

ICO Girona - Hospital Dr Josep Trueta (Institut Catala d'Oncologia)

Girona, 17007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico Universitario De Valencia

Valencia, 46010, Spain

Location

Hôpitaux Universitaires de Genève - HUG

Geneva, 1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

University Hospitals Birmingham NHS - UHB-Queen Elisabeth MC

Birmingham, B15 2TH, United Kingdom

Location

University College London Hospitals (UCLH) - NHS Foundation Trust

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Royal Marsden Hospital - site: Sutton, Surrey

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Wagner AD, Grabsch HI, Mauer M, Marreaud S, Caballero C, Thuss-Patience P, Mueller L, Elme A, Moehler MH, Martens U, Kang YK, Rha SY, Cats A, Tokunaga M, Lordick F. EORTC-1203-GITCG - the "INNOVATION"-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group. BMC Cancer. 2019 May 24;19(1):494. doi: 10.1186/s12885-019-5675-4.

  PMID: 31126258 DERIVED

• Integration of Trastuzumab, with or without Pertuzumab, into Perioperative Chemotherapy of HER2- Positive Stomach Cancer: The INNOVATION Trial (EORTC-1203-GITCG). Oncol Res Treat. 2016;39(3):153-4; discussion 155. doi: 10.1159/000444702. No abstract available.

  PMID: 27486629 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Cisplatin; Fluorouracil; Capecitabine; Trastuzumab; pertuzumab; Gastrectomy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Anna Dorothea Wagner, MD

  Centre hospitalier universitaire vaudois, Lausanne

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2014
• First Posted: July 31, 2014
• Study Start: July 15, 2015
• Primary Completion: December 22, 2022
• Study Completion: December 31, 2024
• Last Updated: July 31, 2025

Record last verified: 2025-07

Locations

GB (4); BE (1); PT (2); KR (9); IT (3); ES (1); NO (1); FR (5); DE (11); SG (1); NL (2); CH (2)