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

NCT03443856 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: EORTC 1707-GITCG2018-000406-36
• Study Type: interventional
• Target: 197
• Locations: 9 countries
• Sites: 28

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

Outcome Measures

Primary Outcomes (1)

• 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.

  22 months after last patient in

Secondary Outcomes (5)

• Overall survival (OS)

  5 years after last patient in

• Loco-regional failure rates

  5 years after last patient in

• Distant failure rates

  5 years after last patient in

• Rate of adverse events according to NCI-CTCAE

  5 years after last patient in

• Quality of life assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3

  questionnaires will be completed at baseline, week 6, 3 months, 6 months, 9 months, 12 months, 15 months

Study Arms (2)

chemotherapy arm

OTHER

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

Other: chemotherapy

immunotherapy arm

EXPERIMENTAL

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.

Drug: Nivolumab and Ipilimumab

Interventions

Nivolumab and Ipilimumab 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

immunotherapy arm

chemotherapy OTHER

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

chemotherapy arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (28)

Masaryk Memorial Cancer Institute

Brno, Czechia

Location

University Hospital Hradec Kralove

Hradec Králové, Czechia

Location

CHRU de Lille - Hopital Huriez

Lille, France

Location

Hôpital Privé Jean Mermoz

Lyon, France

Location

Gustave Roussy

Villejuif, France

Location

Charite - Universitaetsmedizin Berlin

Berlin, Germany

Location

Kliniken Essen-Mitte

Essen, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center

Hamburg, Germany

Location

SLK-Kliniken Heilbronn

Heilbronn, Germany

Location

Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden

Leipzig, Germany

Location

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

München, Germany

Location

Universitaetsklinikum Tuebingen-Uni Kliniken Berg

Tübingen, Germany

Location

Rambam Health Care Campus, Oncology Institute

Haifa, Israel

Location

Rabbin Medical Centre - Tel Aviv

Tel Aviv, Israel

Location

Azienda Ospedaliera a Papa Giovanni XXIII

Bergamo, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Napoli, Italy

Location

Oslo University Hospital - Ullevaal Hospital

Oslo, Norway

Location

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, 02 781, Poland

Location

Institut Catalan d'Oncologia - ICO Badalona

Badalona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Complejo Hospitalario A

Pamplona, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

Cambridge University Hospital NHS

Cambridge, United Kingdom

Location

Royal Marsden Hospital

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Royal Marsden Hospital

Sutton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32083013 DERIVED

MeSH Terms

Interventions

Nivolumab; Ipilimumab; Drug Therapy

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Study Officials

• Florian Lordick

  Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden, Leipzig, Germany

  STUDY CHAIR

• Maren Knoedler

  Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden, Leipzig, Germany

  STUDY CHAIR

• Elizabeth Smyth

  Cambridge University Hospital NHS - Cambridge, UK

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2018
• First Posted: February 23, 2018
• Study Start: July 17, 2019
• Primary Completion: December 12, 2023
• Study Completion: June 1, 2026
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2); NO (1); CZ (2); FR (3); PL (1); DE (8); GB (4); ES (4); IT (3)