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

NCT02205047

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: EORTC-1203-GITCG
  • SECONDARY ID: 2014-000722-38
  • SECONDARY ID: MO28922
  • NCT ID: NCT02205047

Conditions

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

Interventions

DrugSynonymsArms
CisplatinStandard chemotherapy
5-fluorouracil or CapecitabineStandard chemotherapy
TrastuzumabExperimental arm 1
PertuzumabExperimental arm 2

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Standard chemotherapyActive ComparatorCisplatin/capecitabine or cisplatin/5-fluorouracil
  • Cisplatin
  • 5-fluorouracil or Capecitabine
Experimental arm 1ExperimentalCisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab
  • Cisplatin
  • 5-fluorouracil or Capecitabine
  • Trastuzumab
Experimental arm 2Experimentalcisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab
  • Cisplatin
  • 5-fluorouracil or Capecitabine
  • Trastuzumab
  • Pertuzumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Near Complete Pathological Response Rate
Time Frame:After 3 cycles (21 days) of neoadjuvant chemotherapy
Safety Issue:
Description: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

Measure:Locoregional failure
Time Frame:At the time of surgery and at 5 years
Safety Issue:
Description:
Measure:R0 resection rate
Time Frame:At the time of surgery
Safety Issue:
Description:
Measure:Distant failure
Time Frame:At the time of surgery and at 5 years
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:5 years after LPI
Safety Issue:
Description:
Measure:Recurrence-free survival
Time Frame:5 years after LPI
Safety Issue:
Description:
Measure:Overall survival
Time Frame:5 years after LPI
Safety Issue:
Description:
Measure:Toxicity
Time Frame:5 years after LPI
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:European Organisation for Research and Treatment of Cancer - EORTC

Trial Keywords

  • Neoadjuvant chemotherapy

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