Postoperative Immunotherapy vs Standard Chemotherapy for Gastric Cancer With High Risk for Recurrence

NCT ID: NCT03443856

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 197 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-17
• Study Completion Date: 2026-06-30

Brief Summary

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

Conditions

Gastric and Esophagogastric Junction Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

chemotherapy arm

Completion of the perioperative treatment according to the 2016 ESMO guidelines (change of regimen is not allowed).

Group Type: OTHER

chemotherapy

Intervention Type: OTHER

Completion of the perioperative treatment according to the 2016 ESMO guidelines (change of regimen is not allowed).

immunotherapy arm

Treatment: 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. No chemotherapy.

Group Type: EXPERIMENTAL

Nivolumab and Ipilimumab

Intervention Type: DRUG

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

Interventions

Nivolumab and Ipilimumab

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

Intervention Type: DRUG

chemotherapy

Completion of the perioperative treatment according to the 2016 ESMO guidelines (change of regimen is not allowed).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Histologically proven gastric, lower esophageal or GE-junction adenocarcinoma (Siewert I-III)
• Subjects must have completed pre-operative chemotherapy with a fluoropyrimidine-platinum containing regimen and macroscopically complete surgery prior to randomization
• Minimal duration of neoadjuvant chemotherapy should be 6 weeks, maximum 12 weeks.
• Total or distal gastrectomy with D2 lymphadenectomy according to ESMO guidelines should have been completed for gastric and junctional Siewert type III cancers. Ivor Lewis or McKeown oesophagectomy with two field lymphadenectomy should have been performed for junctional Siewert type I cancers. For Siewert type II cancers either total gastrectomy with D2-lymphadenectomy or oesophagectomy with two field lymphadenectomy should have been completed. Open, minimal invasive or hybrid surgical approaches are acceptable as long as the requirements above are fulfilled.
• Regardless of the type of surgery a minimum of 15 lymph nodes should have been resected and examined.
• Recovered from surgery and fit for study treatment as assessed by a multidisciplinary team. Surgery should have been completed 2 to 3 months before randomization.
• ypN1-3 status according to current (8th) version of TNM classification system. In case of an ypN0 status patients must meet the inclusion criterion of R1 resection.
• R0 or R1 resection according to current (8th) version of TNM classification system. In case of R0 resection, patients must meet the inclusion criterion of ypN1-3
• WHO performance status score of 0 or 1
• Age ≥ 18 years
• Adequate organ function assessed within 7 days before randomization:
• White blood cell count (WBC) > 2 x 109/L
• Absolute neutrophil count (ANC) > 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL
• Measured/calculated creatinine clearance ≥ 60 mL/min (according to Cockroft-Gault formula).
• 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) ≤ 1.5ULN
• Cardiac assessment by 12 Lead ECG and if clinically indicated, cardiac function assessment (using either echocardiography or MUGA scan)
• All toxicities (exception alopecia) attributed to prior anti-cancer therapy must have resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug.
• Women of childbearing potential (WOCBP*) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)) within 24 hours prior to randomization
• Men who are sexually active with an WOCBP must adhere to contraception (condom) during the study and for a period of 7 months after the last dose of the study treatment in the experimental arm and 6 months in the control arm.
• Patients of childbearing / reproductive potential should use highly effective method of birth control measures during the study treatment period and for at least 5 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria

• R2 resection status
• M1 stage according to current (8th) version of TNM classification system
• Patients who have undergone complete resection of metastases
• Impaired renal, hepatic, cardiac, pulmonary or endocrine status that compromises the eligibility of the patient for postoperative chemotherapy or immunotherapy
• Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina pectoris, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious cardiac arrhythmia requiring medication
• Subjects with active, known, or suspected infectious or autoimmune disease
• Patients who have received antibiotics within the last 14 days before randomization are excluded.
• Subjects with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll
• Subjects with a condition requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration
• Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Subjects with > Grade 1 peripheral neuropathy
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Prior or concomitant treatment with radiotherapy/radiochemotherapy
• Any positive test result for HBV or HCV indicating acute or chronic infection
• Known history of HIV or known AIDS and, if required by local practice or positive HIV testing at screening
• Known uncontrollable hypersensitivity to the components of cisplatin/oxaliplatin, fluorouracil (5-FU) or capecitabine, epirubicine or docetaxel
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Ongoing or concomitant use of the antiviral drug sorivudine or its chemically related analogs, such as brivudine.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Florian Lordick

Role: STUDY_CHAIR

Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden, Leipzig, Germany

Maren Knoedler

Role: STUDY_CHAIR

Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden, Leipzig, Germany

Elizabeth Smyth

Role: STUDY_CHAIR

Cambridge University Hospital NHS - Cambridge, UK

Locations

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

Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden

Leipzig, , Germany

Klinikum Rechts der isar Der Technische Universitaet Muenchen - Klinikum Rechts Der Isar

München, , Germany

Universitaetsklinikum Tuebingen-Uni Kliniken Berg

Tübingen, , Germany

Rambam Health Care Campus, Oncology Institute

Haifa, , Israel

Rabbin Medical Centre - Tel Aviv

Tel Aviv, , Israel

Azienda Ospedaliera a Papa Giovanni XXIII

Bergamo, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Napoli, , Italy

Oslo University Hospital - Ullevaal Hospital

Oslo, , Norway

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, , Poland

Institut Catalan d'Oncologia - ICO Badalona

Badalona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Complejo Hospitalario A

Pamplona, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Cambridge University Hospital NHS

Cambridge, , United Kingdom

Royal Marsden Hospital

London, , United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Royal Marsden Hospital

Sutton, , United Kingdom

Countries

Czechia; France; Germany; Israel; Italy; Norway; Poland; Spain; United Kingdom

References

Smyth E, Knodler M, Giraut A, Mauer M, Nilsson M, Van Grieken N, Wagner AD, Moehler M, Lordick F. VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): An Open Label Randomized Controlled Phase-2-Study. Front Oncol. 2020 Jan 30;9:1320. doi: 10.3389/fonc.2019.01320. eCollection 2019.

Reference Type: DERIVED

PMID: 32083013 (View on PubMed)

Other Identifiers

2018-000406-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC 1707-GITCG

Identifier Type: -

Identifier Source: org_study_id