INtegratioN of trastuzumab, with or without pertuzumab, into periOperatiVe chemotherApy of HER-2 posiTIve stOmach caNcer: the INNOVATION-TRIA
- Conditions
- stomach cancer10017991
- Registration Number
- NL-OMON53087
- Lead Sponsor
- European Organisation for Research in Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 3
* All patients (HER-2 positive and negative) should be registered in the
trial as soon as possible after written informed consent for screening
according to ICH/GCP, and national/local regulations.
* Histologically proven, gastric or GE-junction adenocarcinoma (Siewert I-III)
* Absence of distant metastases on CT scan of thorax and abdomen
* Patient medically fit for gastrectomy/oesophagectomy as decided by the
investigator
* Age >= 18 years
* WHO performance status 0 - 1,
Randomization:
- HER-2 overexpression, as determined by central testing using
immunohistochemistry (IHC 3+) or the combination of IHC 2+ and HER-2 FISH
positive.
* Amenable to gastrectomy/oesophagectomy with curative intent as confirmed by a
multidisciplinary team discussion
* UICC (7th edition) tumor stage Ib to III, as defined by CT scan and/or MRI.
Endosonography (EUS) is recommended, but not mandatory. EUS should especially
be considered to distinguish T1 and T2 tumors and to evaluate local
resectability. (In case of conflicting results of CT scan and/or MRI and
endoscopic ultrasound, the final decision on which finding the staging is based
should be taken by the multidisciplinary team).
- The cardiac ejection fraction (LVEF), as determined by echocardiography,
MUGA or cardiac MRI should be at least 55%.
* Adequate organ function:
* White blood cell count (WBC) > 3 x 109/L
* Absolute neutrophil count (ANC) > 1.5 x 109/L
* Platelets >= 100 x 109/L
* Hemoglobin >= 9 g/dL (transfusions are permitted to reach this value)
* Estimated glomerular filtration rate (eGFR) according to MDRD should be > 50
ml/min for patients treated with oxaliplatin-based regimens upfront
Note: for patients that will receive CISPLATIN upfront, a GFR > 60 ml/min is
required
* Total bilirubin within normal limits (if the patient has documented Gilbert*s
disease <= 1.5 × ULN or direct bilirubin <= ULN)
* Aspartate transaminase (AST) and alanine transaminase (ALT) <= 2.5 × ULN
- Absence of preexisting neuropathy > grade I
- Investigator and patient have to agree to replace any oral anticoagulations
by subcutaneous administration of low-molecular weight heparin
- Absence of any psychological, familial, sociological or geographical
condition potentially hampering compliance with study protocol & follow-up
schedule;
- For women who are not postmenopausal (> 12 months of nontherapy 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 treatment period &for at
least 7 months after last
treatment dose
- Negative serum pregnancy test
- For men: agreement to remain abstinent or use a condom plus additional
contraceptive method that together result in a failure rate of < 1% per year
during the treatment period &for at least 7
months after last dose of study treatment.
* No prior chemo- or antibody therapy
* No history of significant cardiac disease defined as:
* Symptomatic CHF (NYHA classes II-IV, see Appendix D)
* High-risk uncontrolled arrhythmias, i.e. atrial tachycardia with a
heart rate > 100/min at rest, significant ventricular arrhythmia
(ventricular tachycardia) or higher-grade AV-block (second degree AV-block Type
2 [Mobitz 2] or third degree AV-block)
* History of myocardial infarction within 6 months prior to randomization
* Clinically significant valvular heart disease
* No central nervous system metastasis or leptomeningeal tumor spread. For
patients without any neurological symptoms, a brain MRI is recommended, but not
obligatory. For patients with any clinical symptoms which may be attributed to
brain metastases, a brain MRI is compulsory to rule out cerebral metastases.
* No known hypersensitivity to the components of trastuzumab, pertuzumab,
cisplatin, oxaliplatin, docetaxel, 5-FU or capecitabine
- no patients with interstitial lung disease
* Absence of preexisting neuropathy > grade I
* No known dihydropyrimidine dehydrogenase (DPD) deficiency (testing not
required). In case of specific recommendations due to institutional and/or
national guidelines please proceed accordingly.
* No ongoing or concomitant use of the antiviral drug sorivudine or its
chemically related analogs, such as brivudine
* No chronic treatment with high-dose intravenous corticosteroids (> 10 mg/day
prednisone equivalents)
* No 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.
* Female patients should not be breast feeding.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is major pathological response rate (< 10% vital residual<br /><br>tumor cells).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints are:<br /><br>* R0 resection rate<br /><br>* Pathological complete response<br /><br>* Locoregional failure<br /><br>* Distant failure<br /><br>* Progression-free survival according to RECIST v1.1<br /><br>* Recurrence-free-survival (from surgery)<br /><br>* Overall survival<br /><br>* Adverse event assessment according to CTCAE v 4.0</p><br>