Resectable gastric or gastroesophageal junction adenocarcinoma MedDRA version: 21.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: SPARTALIZUMAB
Product Code: PDR001
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: SPARTALIZUMAB
Current Sponsor code: PDR001
Concentration unit: mg milligram(s)
Concentr
Sponsors
Centre François Baclesse
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years - Untreated localized gastric or GEJ adenocarcinoma considered resectable (clinical stage =cT2 and/or cN+ and no metastasis) - Histologically confirmed adenocarcinoma - ECOG performance status score of 0 or 1 - All subjects must consent to allow the acquisition of blood samples and fresh tumor samples for performance of correlative studies. - Screening laboratory values must meet the following criteria: o WBC = 2000/ mm³ o Neutrophils = 1500/ mm³ o Platelets = 100 000/ mm³ o Hemoglobin = 9.0 g/dL o Bilirubin = 1.5 x ULN, AST and ALT = 3 x ULN o Serum creatinine = 1.5 x ULN or measured or calculated creatinine = 50 ml/min clearance (CrCl) (using the Cockcroft-Gault formula) - Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72h before study start - Subjects in reproductive age must be willing to use adequate contraception during the study and at least 6 months after the last dose of investigational drug - Subjects affiliated to a social security regimen - Patient has signed informed consents obtained before any trial related activities and according to local guidelines Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: - Subject with any distant metastasis - Subject with no recovering from the effects of major surgery or significant traumatic injury within 14 days before inclusion - Documented significant cardiovascular disease within the past 6 months before the first dose of study treatment, including: history of congestive heart failure (defined as NYHA III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis - History of other malignancy within the previous 3 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma) - Subject with active, known, or suspected autoimmune disease - Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment - Subject with symptomatic interstitial lung disease - Known history of HIV or HBV infection - Known active HCV infection - Known history of active tuberculosis - Vaccination with live vaccine within 30 days before the first dose of study treatment - Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways - Prior anticancer therapy for the current malignancy - Known hypersensitivity to any of the study drugs or their excipients - Chronic inflammable gastro-intestinal disease - Uracilemia = 16 ng/ml - QT/QTc > 450 msec for men and > 470 msec for women - Peripheral neuropathy = Grade II - Uncontrolled diabetes - Active infection requiring systemic therapy - Participation in another therapeutic clinical study - Patient deprived of liberty or placed under the authority of a tutor - Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the pathologic response after pre-operative treatment;Secondary Objective: - To evaluate the impact of perioperative treatment on survival outcomes - To evaluate the histological R0 resection margin - To establish the association between pCR response and survival outcomes - To determine the safety profile of the combination Spartalizumab + FLOT regimen - To evaluate the post-operative morbidity and mortality - To evaluate the ctDNA levels over time - To determine potential biomarkers associated with clinical efficacy. These biomarkers may include: - PD-L1 expression measured as the CPS - TMB, including MSI status - EBV status - To compare the characteristics of the initial tumor with the organoids cultures - To evaluate treatment responses with tumor organoid cultures ;Primary end point(s): The primary endpoint is the proportion of patients with pCR in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist.;Timepoint(s) of evaluation of this end point: During the surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - DFS defined as time between inclusion and first progression according to RECIST v1.1 criteria or death whatever cause (in the absence of progression); patients without disease progression or death at the time of analysis will be censored at the time of the latest date of assessment. - OS defined as the time between inclusion and death whatever cause; any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. - Proportion of patients with margin-free resection (R0), defined as a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed - Correlation between pCR and DFS - Correlation between pCR and OS - Toxicities of the combination Spartalizumab + FLOT regimen according to NCI CTCAE criteria v5.0 - Post-operative morbidity, defined post-operative complications grades II-V according to Clavien-Dindo classification during surgery, within 30 days after surgery or during the hospital stay - Post-operative mortality, defined as the rate of patients died due to any cause during the 30 days post-surgery Exploratory end point: - To evaluate the ctDNA levels over time - To determine potential biomarkers associated with clinical efficacy by analyzing biomarker measures. These biomarkers may include: - PD-L1 expression measured as the CPS - TMB, including MSI status - EBV status - To compare the characteristics of the initial tumor with the organoids cultures - To evaluate treatment responses with tumor organoid cultures ;Timepoint(s) of evaluation of this end point: up to disease progression | — |
Countries
France
Contacts
Public ContactLECONTE
Centre François Baclesse
Outcome results
None listed