The primary objective of the trial is to investigate if nivolumab plus ipilimumab given as adjuvant treatment improve disease free survival (DFS) in patients with stage Ib-IVa gastric and esophagogastric junction adenocarcinoma and high risk of recurrence (defined by ypN1-3 and/or R1 status) following neoadjuvant chemotherapy and resection. Other study objectives: * To investigate the safety and effect of adjuvant immunotherapy on long term oncologic outcomes and quality of life of patients in the study * To correlate nutritional status assessment on outcomes and quality of life of patients
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
197
Nivolumab 1 mg/kg IV Q3W plus Ipilimumab 3 mg/kg IV Q3W for 4 cycles (3 months) followed by nivolumab 240 mg flat-dose IV Q2W for 9 months.Total treatment time 1 year
Completion of the perioperative treatment according to the 2016 ESMO guidelines (change of regimen is not allowed).
Masaryk Memorial Cancer Institute
Brno, Czechia
University Hospital Hradec Kralove
Hradec Králové, Czechia
CHRU de Lille - Hopital Huriez
Lille, France
Hôpital Privé Jean Mermoz
Lyon, France
Gustave Roussy
Villejuif, France
Charite - Universitaetsmedizin Berlin
Berlin, Germany
Kliniken Essen-Mitte
Essen, Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, Germany
Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center
Hamburg, Germany
SLK-Kliniken Heilbronn
Heilbronn, Germany
...and 18 more locations
Disease free survival (DFS)
Disease free survival is defined as the time interval between randomization and the date of disease recurrence or death from any cause, whichever comes first. Patients alive with no disease recurrence are censored at the date of the last follow-up examination. randomization and the date of disease recurrence or death from any cause, whichever comes first.
Time frame: 22 months after last patient in
Overall survival (OS)
Overall survival is defined as the time interval between the date of randomization and the date of death from any cause. Patients who are still alive when last traced are censored at the date of last follow up.
Time frame: 5 years after last patient in
Loco-regional failure rates
Local recurrence is defined as evidence of tumor in the anastomotic area. Regional recurrence is defined as evidence of tumor in the locoregional lymph nodes or other surrounding structures apart from the anastomotic site. Death in absence of loco-regional failure will be considered as a competing risk in the estimation of the cumulative incidence of loco-regional failures. Patients who have not had any such event at the time of data analysis will be censored at the date of the last follow-up examination.
Time frame: 5 years after last patient in
Distant failure rates
The diagnosis of distant recurrence requires imaging confirmed by pathology. Once recurrence is confirmed, the date of recurrence is the first date when recurrence was suspected. Distant recurrence is defined as recurrence not considered as local or regional.Death in absence of distant failure will be considered as a competing risk in the estimation of the cumulative incidence of distant failures. Patients who have not had any such event at the time of data analysis will be censored at the date of the last follow-up examination
Time frame: 5 years after last patient in
Rate of adverse events according to NCI-CTCAE
All adverse events will be recorded; the investigator will assess whether those events are drug related (reasonable possibility, no reasonable possibility) and this assessment will be recorded in the database for all adverse events. AEs will be collected at baseline from randomization. Only the worst grade per CTCAE category will be recorded per cycle. All adverse events must be followed until resolution or stabilization. Adverse Events of Special Interest for ipilimumab and nivolumab requiring a close follow-up were identified as a result of signals observed from previous studies involving the protocol treatments. These events require a close follow-up
Time frame: 5 years after last patient in
Quality of life assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3
Quality of life will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3. These include five functional scales (physical, role, emotional, social, and cognitive), three symptom (fatigue, nausea and vomiting and pain) and a global health status/QoL scale and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). The primary HRQoL endpoints that are considered relevant for this study are global health status/QoL and physical functioning.A difference of 10 points on the 100-point QLQ-C30 scale between the two arms will be considered as clinically relevant
Time frame: questionnaires will be completed at baseline, week 6, 3 months, 6 months, 9 months, 12 months, 15 months
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