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

July 30, 2025 updated by: European Organisation for Research and Treatment of Cancer - EORTC

INtegratioN of Trastuzumab, With or Without Pertuzumab, Into periOperatiVe chemotherApy of HER-2 posiTIve stOmach caNcer: the INNOVATION-TRIAL

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a randomized phase II trial with an internal control. The randomization will be a 1:2:2 randomization (control: experimental arm 1: experimental arm 2). Potentially eligible patients will be screened centrally for the HER-2 status. After confirmation of HER-2 positive disease, eligible patients will be centrally randomized through the EORTC randomization system. A minimization technique will be used for random treatment allocation between the three treatment arms. Stratification will be done by histological subtype (intestinal/non-intestinal); Korea versus Europe; stage II versus III; node positive versus node negative.

Study Type

Interventional

Enrollment (Actual)

172

Phase

  • Phase 2

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

  • Belgium
    • Vlaanderen
      • Gent, Vlaanderen, Belgium, 9000
        • University Hospital Gent
  • Estonia
      • Tallinn, Estonia, 13419
        • North Estonia Medical Centre
  • France
      • Besançon, France, 25030
        • CHRU de Besancon - Hopital Jean Minjoz
      • Lille, France, 59037
        • CHRU de Lille - Hopital Huriez
      • Pessac, France, 33075
        • CHU de Bordeaux - Group Hospitalier Sud - Hopital Haut-Lévêque
      • Reims, France, 51092
        • CHU de Reims - Hôpital Robert Debré
      • Villejuif, France
        • Institut Gustave Roussy
  • Germany
      • Berlin, Germany, 13353
        • Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
      • Dresden, Germany, 01307
        • Universitaetsklinikum Carl Gustav Carus
      • Essen, Germany, 45136
        • Kliniken Essen-Mitte - Evang. Huyssens-Stiftung
      • Göttingen, Germany, 37075
        • Universitaetsmedizin Goettingen - Georg-August Universitaet
      • Hamburg, Germany, 22291
        • Asklepios Kliniken GmbH - Asklepios Klinik Barmbek
      • Heilbronn, Germany, 74078
        • SLK-Kliniken Heilbronn GmbH
      • Leer, Germany, 26789
        • Onkologische Unter-Ems (Leer-Papenburg-Emden)
      • Leipzig, Germany
        • Universitaetsklinikum Leipzig
      • Mainz, Germany, 55101
        • Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center
      • München, Germany, 81377
        • Ludwig-Maximilians-Universitaet München - Campus Grosshadern
      • München, Germany
        • Technische Universität München - Klinikum Rechts der Isar
  • Italy
      • Bergamo, Italy, 24127
        • Azienda Ospedaliera Papa Giovanni XXIII
      • Milano, Italy, 20141
        • Istituto Europeo Di Oncologia
      • Torino, Italy
        • Azienda Ospedaliera Ordine Mauriziano di Torino
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Asan Medical Center
      • Seoul, Korea, Republic of, 135-720
        • Gangnam Severance Hospital
      • Seoul, Korea, Republic of
        • Gangnam Severance Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of
        • Hallym University Sacred Heart Hospital
      • Seoul, Korea, Republic of, 14068
        • Hallym University Sacred Heart Hospital
      • Seoul, Korea, Republic of
        • Severance Hospital YUCM
      • Seoul, Korea, Republic of
        • Severance Hospital, Yonsei University Health System (YUCM)
      • Suwon-Si Gyeonggi-do, Korea, Republic of, 16247
        • The Catholic University of Korea-St. Vincent's Hospital
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
      • Amsterdam, Netherlands, 1081 HV
        • Academisch Medisch Centrum - UMC Universiteit van Amsterdam - site: VUMC
  • Norway
      • Oslo, Norway, 0379
        • Oslo University Hospital - Radiumhospitalet
  • Portugal
      • Lisboa, Portugal
        • Instituto Portugues de Oncologia de Lisboa Francisco Gentil
      • Porto, Portugal, 4200-072
        • Instituto Portugues De Oncologia - Centro Do Porto
  • Singapore
      • Singapore, Singapore, 169610
        • National Cancer Centre Singapore
  • Spain
      • Badalona, Spain, 08916
        • ICO Badalona (Institut Catala d'Oncologia) - Hospital Germans Trias i Pujol
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron - Institut Oncologia
      • Girona, Spain, 17007
        • ICO Girona - Hospital Dr Josep Trueta (Institut Catala d'Oncologia)
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
        • Institut Catala d'Oncologia - ICO L'Hospitalet
  • Switzerland
      • Geneve, Switzerland, 1211
        • Hopitaux Universitaires de Geneve - HUG
      • Lausanne, Switzerland
        • Centre Hospitalier Universitaire Vaudois
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • University Hospitals Birmingham NHS - UHB-Queen Elisabeth MC
      • London, United Kingdom
        • University College London Hospitals (UCLH) - NHS Foundation Trust
      • Manchester, United Kingdom
        • The Christie NHS Foundation Trust
      • Sutton, United Kingdom, SM2 5PT
        • Royal Marsden Hospital - site: Sutton, Surrey

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

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard chemotherapy
Cisplatin/capecitabine or cisplatin/5-fluorouracil
Drug: Cisplatin
Drug: 5-fluorouracil or Capecitabine
Procedure: gastrectomy
D2 gastrectomy
Experimental: Experimental arm 1
Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab
Drug: Cisplatin
Drug: Trastuzumab
Drug: 5-fluorouracil or Capecitabine
Procedure: gastrectomy
D2 gastrectomy
Experimental: Experimental arm 2
cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab
Drug: Cisplatin
Drug: Pertuzumab
Drug: Trastuzumab
Drug: 5-fluorouracil or Capecitabine
Procedure: gastrectomy
D2 gastrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Near Complete Pathological Response Rate
Time Frame: After 3 cycles (21 days) of neoadjuvant chemotherapy
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 Outcome Measures

Outcome Measure
Time Frame
Locoregional failure
Time Frame: At the time of surgery and at 5 years
At the time of surgery and at 5 years
R0 resection rate
Time Frame: At the time of surgery
At the time of surgery
Distant failure
Time Frame: At the time of surgery and at 5 years
At the time of surgery and at 5 years
Progression-free survival
Time Frame: 5 years after LPI
5 years after LPI
Recurrence-free survival
Time Frame: 5 years after LPI
5 years after LPI
Overall survival
Time Frame: 5 years after LPI
5 years after LPI
Toxicity
Time Frame: 5 years after LPI
5 years after LPI

Collaborators and Investigators

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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Anna Dorothea Wagner, MD, Centre hospitalier universitaire vaudois, Lausanne

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)

July 15, 2015

Primary Completion (Actual)

December 22, 2022

Study Completion (Actual)

December 31, 2024

Study Registration Dates

First Submitted

July 10, 2014

First Submitted That Met QC Criteria

July 29, 2014

First Posted (Estimated)

July 31, 2014

Study Record Updates

Last Update Posted (Actual)

July 31, 2025

Last Update Submitted That Met QC Criteria

July 30, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-1203-GITCG
  • 2014-000722-38 (EudraCT Number)
  • MO28922 (Other Grant/Funding Number: Roche)

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.

Clinical Trials on Malignant Neoplasm of Stomach

Clinical Trials on Cisplatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe