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.
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
Drug | Synonyms | Arms |
---|
Cisplatin | | Experimental arm 1 |
5-fluorouracil or Capecitabine | | Experimental arm 1 |
Trastuzumab | | Experimental arm 1 |
Pertuzumab | | Experimental 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
Name | Type | Description | Interventions |
---|
Standard chemotherapy | Active Comparator | Cisplatin/capecitabine or cisplatin/5-fluorouracil | - Cisplatin
- 5-fluorouracil or Capecitabine
|
Experimental arm 1 | Experimental | Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab | - Cisplatin
- 5-fluorouracil or Capecitabine
- Trastuzumab
|
Experimental arm 2 | Experimental | cisplatin/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
Last Updated
February 5, 2018