Adjuvant Immunotherapy in Patients With Resected Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): an Open Label Randomized Controlled Phase-2-study
Postoperative Immunotherapy vs Standard Chemotherapy for Gastric Cancer With High Risk for Recurrence
Sponsors
Source
European Organisation for Research and Treatment of Cancer - EORTC
Oversight Info
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
No
Is Us Export
Yes
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
Overall Status
Recruiting
Start Date
2019-07-17
Completion Date
2026-06-01
Primary Completion Date
2023-04-01
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Disease free survival (DFS) |
22 months after last patient in |
Secondary Outcome
Measure |
Time Frame |
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 |
Enrollment
240
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
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
Arm Group Label
immunotherapy arm
Intervention Type
Other
Intervention Name
Description
Completion of the perioperative treatment according to the 2016 ESMO guidelines (change of regimen is not allowed).
Arm Group Label
chemotherapy arm
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. Ideally, surgery should have been completed 1 month before at the maximum.
- 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
- Availability of operative and pathology reports for review
- 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
- 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.
- Availability of tumor tissue from the resected site of disease must be provided for
biobanking
- 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
- 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 5 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
- Subjects with previous malignancies are excluded unless a complete remission or
complete resection was achieved at least 5 years prior to study entry. Adequately
treated cervical carcinoma in situ, and localized non-melanoma skin cancer are no
exclusion criteria, regardless of timepoint of diagnosis.
- 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 testing positive for HIV or known AIDS
- 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.
Gender
All
Minimum Age
N/A
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Florian Lordick |
Study Chair |
Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden, Leipzig, Germany |
Maren Knoedler |
Study Chair |
Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden, Leipzig, Germany |
Elizabeth Smyth |
Study Chair |
Cambridge University Hospital NHS - Cambridge, UK |
Overall Contact
Location
Facility |
Status |
Investigator |
Masaryk Memorial Cancer Institute Brno Czechia |
Not yet recruiting |
Last Name: Radka Obermannova Role: Principal Investigator |
Hôpital Privé Jean Mermoz Lyon France |
Not yet recruiting |
Last Name: Pascal Artru Role: Principal Investigator |
Gustave Roussy Villejuif France |
Not yet recruiting |
Last Name: Valérie Boige, Dr. Role: Principal Investigator |
SLK-Kliniken Heilbronn Heilbronn Germany |
Recruiting |
Last Name: Uwe Martens Role: Principal Investigator |
Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden Leipzig Germany |
Recruiting |
Last Name: Florian Lordick |
Rambam Health Care Campus, Oncology Institute Haifa Israel |
Not yet recruiting |
Last Name: Irit Ben-Aharon Role: Principal Investigator |
Rabbin Medical Centre - Tel Aviv Tel Aviv Israel |
Not yet recruiting |
Last Name: Baruch Brenner Role: Principal Investigator |
Azienda Ospedaliera a Papa Giovanni XXIII Bergamo Italy |
Not yet recruiting |
Last Name: Mario Mandala Role: Principal Investigator |
Istituto Europeo di Oncologia Milan Italy |
Not yet recruiting |
Last Name: Alessandra Cella Role: Principal Investigator |
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" Napoli Italy |
Not yet recruiting |
Last Name: Antonio Avallone Role: Principal Investigator |
Oslo University Hospital - Ullevaal Hospital Oslo Norway |
Not yet recruiting |
Last Name: Ghazwan Al-Haidari Role: Principal Investigator |
Maria Sklodowska-Curie Memorial Cancer Centre Warsaw 02 781 Poland |
Not yet recruiting |
Last Name: Lucjan Wyrwicz, Dr. Role: Principal Investigator |
Champalimaud Cancer Centre Lisboa Portugal |
Not yet recruiting |
Last Name: Nuno Couto Role: Principal Investigator |
Instituto Portuguès de Oncologia do Porto Porto Portugal |
Not yet recruiting |
Last Name: Nuno Sousa Role: Principal Investigator |
Institut Catalan d'Oncologia - ICO Badalona Badalona Spain |
Not yet recruiting |
Last Name: Cristina Buges Role: Principal Investigator |
Hospital Universitario 12 de Octubre Madrid Spain |
Recruiting |
Last Name: Carlos Gomez Role: Principal Investigator |
Complejo Hospitalario A Pamplona Spain |
Not yet recruiting |
Last Name: Antonio Viudez Role: Principal Investigator |
Hospital Clinico Universitario de Valencia Valencia Spain |
Not yet recruiting |
Last Name: Andres Cervantes Role: Principal Investigator |
University Hospitals Birmingham NHS Foundation Trust Birmingham United Kingdom |
Not yet recruiting |
Last Name: Victoria Kunene Role: Principal Investigator |
Cambridge University Hospital NHS Cambridge United Kingdom |
Recruiting |
Last Name: Elizabeth Smyth Role: Principal Investigator |
Royal Marsden Hospital London United Kingdom |
Not yet recruiting |
Last Name: Ian Chau Role: Principal Investigator |
University College London Hospitals NHS Foundation Trust London United Kingdom |
Not yet recruiting |
Last Name: Kai-Keen Shiu Role: Principal Investigator |
Royal Marsden Hospital Sutton United Kingdom |
Recruiting |
Last Name: Ian Chau Role: Principal Investigator |
Location Countries
Country
Czechia
France
Germany
Israel
Italy
Norway
Poland
Portugal
Spain
United Kingdom
Verification Date
2019-08-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Has Expanded Access
No
Condition Browse
Secondary Id
2018-000406-36
Number Of Arms
2
Intervention Browse
Mesh Term
Nivolumab
Ipilimumab
Arm Group
Arm Group Label
chemotherapy arm
Arm Group Type
Other
Description
Completion of the perioperative treatment according to the 2016 ESMO guidelines (change of regimen is not allowed).
Arm Group Label
immunotherapy arm
Arm Group Type
Experimental
Description
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.
Firstreceived Results Date
N/A
Acronym
VESTIGE
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
February 19, 2018
Study First Submitted Qc
February 19, 2018
Study First Posted
February 23, 2018
Last Update Submitted
August 26, 2019
Last Update Submitted Qc
August 26, 2019
Last Update Posted
August 27, 2019
ClinicalTrials.gov processed this data on December 13, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.