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

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase: Completed; Phase 2

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

Treatments: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Cisplatin; Drug: 5-fluorouracil or Capecitabine; Procedure: gastrectomy

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT02205047

MO28922 (Other Grant/Funding Number)

EORTC-1203-GITCG

2014-000722-38 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 172 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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172 participants in 3 patient groups

Standard chemotherapy

Active Comparator group

Description:

Cisplatin/capecitabine or cisplatin/5-fluorouracil

Treatment:

Procedure: gastrectomy

Drug: 5-fluorouracil or Capecitabine

Drug: Cisplatin

Experimental arm 1

Experimental group

Description:

Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab

Treatment:

Procedure: gastrectomy

Drug: 5-fluorouracil or Capecitabine

Drug: Cisplatin

Drug: Trastuzumab

Experimental arm 2

Experimental group

Description:

cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab

Treatment:

Procedure: gastrectomy

Drug: 5-fluorouracil or Capecitabine

Drug: Cisplatin

Drug: Pertuzumab

Drug: Trastuzumab