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

Malignant Neoplasm of Stomach Clinical Trial

— INNOVATION  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02205047
• Other study ID #: EORTC-1203-GITCG
• Secondary ID: 2014-000722-38MO
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 15, 2015
• Est. completion date: December 31, 2028

Study information

• Verified date: December 2023
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 171
• Est. completion date: December 31, 2028
• Est. primary completion date: December 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Cisplatin

• 5-fluorouracil or Capecitabine

• Trastuzumab

• Pertuzumab

Procedure:
• gastrectomy
D2 gastrectomy

Locations

Country	Name	City	State
Belgium	University Hospital Gent	Gent	Vlaanderen
Estonia	North Estonia Medical Centre	Tallinn
France	CHRU de Besancon - Hopital Jean Minjoz	Besançon
France	CHRU de Lille - Hopital Huriez	Lille
France	CHU de Bordeaux - Group Hospitalier Sud - Hopital Haut-Lévêque	Pessac
France	CHU de Reims - Hôpital Robert Debré	Reims
France	Institut Gustave Roussy	Villejuif
Germany	Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus	Dresden
Germany	Kliniken Essen-Mitte - Evang. Huyssens-Stiftung	Essen
Germany	Universitaetsmedizin Goettingen - Georg-August Universitaet	Göttingen
Germany	Asklepios Kliniken GmbH - Asklepios Klinik Barmbek	Hamburg
Germany	SLK-Kliniken Heilbronn GmbH	Heilbronn
Germany	Onkologische Unter-Ems (Leer-Papenburg-Emden)	Leer
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center	Mainz
Germany	Ludwig-Maximilians-Universitaet München - Campus Grosshadern	München
Germany	Technische Universität München - Klinikum Rechts der Isar	München
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Istituto Europeo di Oncologia	Milano
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Hallym University Sacred Heart Hospital	Seoul
Korea, Republic of	Severance Hospital YUCM	Seoul
Korea, Republic of	The Catholic University of Korea-St. Vincent's Hospital	Suwon-Si Gyeonggi-do
Netherlands	Academisch Medisch Centrum - UMC Universiteit van Amsterdam - site: VUMC	Amsterdam
Netherlands	The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis	Amsterdam
Norway	Oslo University Hospital - Radiumhospitalet	Oslo
Portugal	Instituto Portugues De Oncologia - Centro Do Porto	Porto
Singapore	National Cancer Centre Singapore	Singapore
Spain	ICO Badalona (Institut Catala d'Oncologia) - Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Universitari Vall d'Hebron - Institut Oncologia	Barcelona
Spain	ICO Girona - Hospital Dr Josep Trueta (Institut Catala d'Oncologia)	Girona
Spain	Institut Catala d'Oncologia - ICO L'Hospitalet	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Clinico Universitario De Valencia	Valencia
Switzerland	Hôpitaux Universitaires de Genève - HUG	Geneve
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	University Hospitals Birmingham NHS - UHB-Queen Elisabeth MC	Birmingham
United Kingdom	Royal Marsden Hospital - site: London Chelsea	London
United Kingdom	University College London Hospitals (UCLH) - NHS Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital - site: Sutton, Surrey	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Estonia,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Norway,  Portugal,  Singapore,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Locoregional failure		At the time of surgery and at 5 years
Secondary	R0 resection rate		At the time of surgery
Secondary	Distant failure		At the time of surgery and at 5 years
Secondary	Progression-free survival		5 years after LPI
Secondary	Recurrence-free survival		5 years after LPI
Secondary	Overall survival		5 years after LPI
Secondary	Toxicity		5 years after LPI