Clinical trial NCT02205047: Neoadjuvant Study Using Trastuzumab or Trastuzumab With Pertuzumab in Gastric or Gastroesophageal Junction Adenocarcinoma
Official title: INtegratioN of Trastuzumab, With or Without Pertuzumab, Into periOperatiVe chemotherApy of HER-2 posiTIve stOmach caNcer: the INNOVATION-TRIAL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Neoplasm of Stomach
Malignant Neoplasm of Cardio-esophageal Junction of Stomach
Epidermal Growth Factor Receptor (EGFR) Protein Overexpression
Keywords: Neoadjuvant chemotherapy
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2014-07-31
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Near Complete Pathological Response Rate
timeFrame: After 3 cycles (21 days) of neoadjuvant chemotherapy
Secondary outcomes:
measure: Locoregional failure
timeFrame: At the time of surgery and at 5 years
measure: R0 resection rate
timeFrame: At the time of surgery
measure: Distant failure
timeFrame: At the time of surgery and at 5 years
measure: Progression-free survival
timeFrame: 5 years after LPI
measure: Recurrence-free survival
timeFrame: 5 years after LPI
measure: Overall survival
timeFrame: 5 years after LPI
measure: Toxicity
timeFrame: 5 years after LPI
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: University Hospital Gent
state: Vlaanderen
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre
city: Besançon
country: France
facility: CHRU de Besancon - Hopital Jean Minjoz
city: Lille
country: France
facility: CHRU de Lille - Hopital Huriez
city: Pessac
country: France
facility: CHU de Bordeaux - Group Hospitalier Sud - Hopital Haut-Lévêque
city: Reims
country: France
facility: CHU de Reims - Hôpital Robert Debré
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus
city: Essen
country: Germany
facility: Kliniken Essen-Mitte - Evang. Huyssens-Stiftung
city: Göttingen
country: Germany
facility: Universitaetsmedizin Goettingen - Georg-August Universitaet
city: Hamburg
country: Germany
facility: Asklepios Kliniken GmbH - Asklepios Klinik Barmbek
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH
city: Leer
country: Germany
facility: Onkologische Unter-Ems (Leer-Papenburg-Emden)
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Mainz
country: Germany
facility: Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center
city: München
country: Germany
facility: Ludwig-Maximilians-Universitaet München - Campus Grosshadern
city: München
country: Germany
facility: Technische Universität München - Klinikum Rechts der Isar
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital YUCM
city: Suwon-Si Gyeonggi-do
country: Korea, Republic of
facility: The Catholic University of Korea-St. Vincent's Hospital
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum - UMC Universiteit van Amsterdam - site: VUMC
city: Oslo
country: Norway
facility: Oslo University Hospital - Radiumhospitalet
city: Porto
country: Portugal
facility: Instituto Portugues De Oncologia - Centro Do Porto
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Catala d'Oncologia - ICO L'Hospitalet
state: Barcelona
city: Badalona
country: Spain
facility: ICO Badalona (Institut Catala d'Oncologia) - Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Institut Oncologia
city: Girona
country: Spain
facility: ICO Girona - Hospital Dr Josep Trueta (Institut Catala d'Oncologia)
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Valencia
country: Spain
facility: Hospital Clinico Universitario De Valencia
city: Geneve
country: Switzerland
facility: Hôpitaux Universitaires de Genève - HUG
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS - UHB-Queen Elisabeth MC
city: London
country: United Kingdom
facility: Royal Marsden Hospital - site: London Chelsea
city: London
country: United Kingdom
facility: University College London Hospitals (UCLH) - NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital - site: Sutton, Surrey
Study officials:
affiliation: Centre hospitalier universitaire vaudois, Lausanne
name: Anna Dorothea Wagner, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.