E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Resectable gastric or gastroesophageal junction adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Resectable gastric or gastroesophageal junction adenocarcinoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the pathologic response after pre-operative treatment |
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E.2.2 | Secondary objectives of the trial |
- 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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to disease progression |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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up to disease progression |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 60 |
E.8.9.1 | In the Member State concerned days | |