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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Cisplatin
* Drug: 5-fluorouracil or Capecitabine
* Drug: Trastuzumab
* Drug: Pertuzumab
* Procedure: gastrectomy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Overall survival |  | 5 years after LPI | 
| Toxicity |  | 5 years after LPI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant chemotherapy