Etude : INNOVATION / EORTC-1203-GITCG (MO28922)



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : INNOVATION / EORTC-1203-GITCG (MO28922)

Situation thérapeutique : Néoadjuvant

Traitement : Thérapie ciblée / Chirurgie

Cadre réglementaire : RIPH1

Dernière MÀJ : 10/01/2022
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : ESSAI INNOVATION : Intégration du trastuzumab, avec ou sans pertuzumab, dans la chimiothérapie péri-opératoire du cancer de l’estomac HER2 positif

Spécialité : Organes digestifs
Localisation : C15 - Tumeur maligne de l'oesophage

Spécialité : Organes digestifs
Localisation : C16 - Tumeur maligne de l'estomac
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : 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.

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.


STUDY ARMS:
- Active Comparator: Standard chemotherapy (Cisplatin/capecitabine or cisplatin/5-fluorouracil) + D2 gastrectomy

- Experimental: Experimental arm 1
Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab + D2 gastrectomy

- Experimental: Experimental arm 2
cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab + D2 gastrectomy


MAIN OBJECTIVE:
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 OBJECTIVES:
1 - R0 resection rate
2 -Pathological complete response
3 - Locoregional failure
4 - Distant failure
5 - Progression-free survival (according to Recist v1.1)
6 - Recurrence-free-survival (from surgery)
7 - Overall survival
8 - Adverse event assessment according to CTCAE v 4.0

Phase : II

Stade : Localisé

1
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1) REGISTRATION
- For determination of the HER-2 status, European sites will have the choice, patient by patient, between the two options:
a) Assessment of HER-2 status of potentially eligible patient in the central lab OR b) Assessment of HER-2 status by IHC only in the local lab & mandatory confirmation of the HER-2 positive result in central lab
In EUROPE: if the site selects option a) FFPE blocks or 20 x 3-5 µm (ideally 20 slides but exceptionally minimum of 15 slides is acceptable) unstained paraffin sections from the diagnostic endoscopic biopsies for all potentially eligible patients must be sent. If site selects option b) & performs local assessment of the HER-2 status by IHC, FFPE blocks or 20 x 3-5 µm (ideally 20 slides, but exceptionally a minimum of 15 slides is acceptable) unstained paraffin sections for all patients with HER-2 IHC status 1+, 2+ or 3+ must be sent for confirmation to central lab
In ASIA all patients are screened locally. Material from patients with a positive HER-2 status (2+ or 3+ by IHC) has to be sent to central lab for confirmation
Asian sites are requested to send only FFPE blocks or 20 x 3-5 µm (ideally 20 slides,but exceptionally a minimum of 15 slides is acceptable)unstained paraffin sections from diagnostic endoscopic biopsies for HER-2 positive patients if 2+ or 3+ by IHC as per local assessment
- All patients (HER-2 positive and negative) should be registered in the trial asap after written informed consent for screening according to ICH/GCP & national/local regulations
- Histologically proven, gastric or GE-junction adenocarcinoma (Siewert I-III)
- Absence of distant metastases on CT scan of thorax & abdomen
- Patient medically fit for gastrectomy/oesophagectomy as decided by investigator
- Age ≥ 18 years
- WHO performance status 0 – 1

2) RANDOMIZATION
- HER-2 overexpression, as determined by central testing using immunohistochemistry (IHC 3+) or the combination of IHC 2+ & HER-2 FISH positive (please see pathology guidelines)
- Amenable to gastrectomy/oesophagectomy with curative intent confirmed by multidisciplinary team discussion
- UICC 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&T2 tumors & 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) & 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 (LMWH) in equivalent doses before treatment start, or if on oral anticoagulations &unwilling to switch to LMWH, patients have to be treated with mandatory 5-FU i.v. instead of capecitabine
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with study protocol & follow-up schedule; those conditions should be discussed with the patient before registration in trial
- 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 treatment period &for at least 7 months after last treatment dose
* Negative serum pregnancy test (β-human chorionic gonadotropin [β-hCG]) result should be available before randomization &within 7 days from treatment start should be performed
- 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. Abstinence is only acceptable if in line with preferred & usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) & withdrawal are not acceptable methods for contraception

Critères de non-inclusion : 2) Randomization
- Prior chemo- or antibody therapy
- 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
- 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.
- Known hypersensitivity to the components of trastuzumab, pertuzumab, oxaliplatin, docetaxel, 5-FU or capecitabine
- Patients with interstitial lung disease
- Known dihydropyrimidine dehydrogenase (DPD) deficiency (testing not required). In case of specific recommendations due to institutional and/or national guidelines please proceed accordingly
- Ongoing or concomitant use of the antiviral drug sorivudine or its chemically related analogs, such as brivudine
- Chronic treatment with high-dose intravenous corticosteroids (> 10 mg/day prednisone equivalents)
- 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
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT02205047
Promoteur :
European Organisation for Research and Treatment of Cancer - EORTC
Type de sponsor : Institutionnel
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Guillaume PIESSEN

TEC / ARC / IDE :
Justine LEROOY
justine.lerooy@
chru-lille.fr
Tel: 03 20 44 47 86 (ou 03 20 44 59 62) Fax: 03 20 44 59 14

Statut de l'essai : CLOS

MAJ : 10/01/2022