Neoadjuvant Study Using Trastuzumab or Trastuzumab With Pertuzumab in Gastric or Gastroesophageal Junction Adenocarcinoma
- Conditions
- Epidermal Growth Factor Receptor (EGFR) Protein OverexpressionMalignant Neoplasm of StomachMalignant Neoplasm of Cardio-esophageal Junction of Stomach
- Interventions
- Procedure: gastrectomy
- Registration Number
- NCT02205047
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 171
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental arm 1 Cisplatin Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab Standard chemotherapy gastrectomy Cisplatin/capecitabine or cisplatin/5-fluorouracil Experimental arm 2 5-fluorouracil or Capecitabine cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab Experimental arm 2 gastrectomy cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab Standard chemotherapy 5-fluorouracil or Capecitabine Cisplatin/capecitabine or cisplatin/5-fluorouracil Experimental arm 1 5-fluorouracil or Capecitabine Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab Experimental arm 1 gastrectomy Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab Experimental arm 2 Cisplatin cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab Standard chemotherapy Cisplatin Cisplatin/capecitabine or cisplatin/5-fluorouracil Experimental arm 1 Trastuzumab Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab Experimental arm 2 Pertuzumab cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab Experimental arm 2 Trastuzumab cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab
- Primary Outcome Measures
Name Time Method Near Complete Pathological Response Rate 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.
- Secondary Outcome Measures
Name Time Method Progression-free survival 5 years after LPI Recurrence-free survival 5 years after LPI 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 Overall survival 5 years after LPI Toxicity 5 years after LPI
Related Research Topics
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Trial Locations
- Locations (43)
University Hospital Gent
🇧🇪Gent, Vlaanderen, Belgium
North Estonia Medical Centre
🇪🇪Tallinn, Estonia
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, France
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Universitaetsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Kliniken Essen-Mitte - Evang. Huyssens-Stiftung
🇩🇪Essen, Germany
Scroll for more (33 remaining)University Hospital Gent🇧🇪Gent, Vlaanderen, Belgium