This is a non-randomized study, open label phase II study. The purpose of this study is to evaluate the complete pathologic response rate (cPRR) with neoadjuvant nivolumab and ipilimumab combination in patients with MSI and/or dMMR localized oeso-gastric cancer.
In patients with resectable oeso-gastric adenocarcinoma, radical surgery is the only curative option. Despite the evolution in treatment with multimodality treatment strategies, oeso-gastric cancer remains one of the most lethal malignancies with 5-year survival rates reaching only 22%. When the disease is localized, perioperative chemotherapy with cytotoxic agents is the preferred strategy since it increases the overall survival (OS) rate. However, in oeso-gastric cancers with microsatellite instability (MSI), is a favorable prognostic factor, the recommended cytotoxic chemotherapy combination seems inefficient and even deleterious. It is now well established that dMMR and or the MSI phenotype are the surrogate markers of response to immunotherapy. The combination of nivolumab and ipilimumab had shown promising efficacy in multiple tumor types (dMMR/MSI). Based on the data above, we have designed this phase II study to evaluate the complete pathological response rate (cPRR) in patients with non-metastatic MSI/dMMR oeso-gastric adenocarcinoma treated with neoadjuvant nivolumab and ipilimumab treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Neo-adjuvant treatment : 240 mg intravenous (I.V.) in 30 minutes - every 2 weeks - 6 cycles \- Adjuvant treatment : 480mg I.V. in 30 minutes - every 4 weeks - 9 cycles
Neo-adjuvant treatment : 1mg/kg over 30 minutes every 6 cycles - 2 cycles
CHRU Jean Minjoz
Besançon, France
Hôpital Henri Mondor
Créteil, France
Institut Hospitalier Franco-Britannique
Levallois-Perret, France
Complete pathological response (cPRR) rate
Each center will assess the pathologic response with a centralized center review in case of cPRR and the analysis will be in intention-to-treat (ITT). cPRR will be defined as complete tumor disappearance of tumor in the low esophagus or the stomach (from 1/3 inferior of the esophagus to pylorus) after surgery anatomopathologic examination according to mandard scale. Surgery will be performed within 5 weeks +\\- 1 week after the last cycle (cycle 6) of neoadjuvant therapy
Time frame: time point when the tumor is examined after the surgery (up to 30 months)
Disease-free survival (DFS)
DFS is defined as the time from the date of starting treatment to local recurrence and/or metastases or death irrespective of cause and censored at the date of last contact.
Time frame: Up to 36 months
Overall Survival (OS)
OS is defined as the time between the date of the first dose of study treatment and the death date. Patients alive at last report will be considered censored at the endpoint. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period.
Time frame: Up to 36 months
Number of participants with treatment-related adverse events
Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v5.0
Time frame: Patients will be assessed for AEs throughout the study at every visit during treatment and at 3-month follow-up visit (3 months after treatment ends). Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs.
Analyze MSI status
Confirmation of MSI and/or dMMR has to be confirmed retrospectively on archival or fresh tumor FFPET block from the primary tumor obtained at the time of the initial diagnosis
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
CHRU Lille
Lille, France
Centre Léon Bérard
Lyon, France
Hôpital Privé Jean Mermoz
Lyon, France
ICM Val d'Aurelle
Montpellier, France
CHU Nantes
Nantes, France
Hôpital Européen Geroges Pompidou
Paris, France
Hôpital Saint Antoine
Paris, France
...and 5 more locations
Time frame: up to 36 months
Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in dMMR tumors
Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in blood of dMMR tumors.
Time frame: Blood samples at baseline, C3D1 and C6D1 of neoadjuvant therapy - cycle every 2 weeks, after surgery at C1 D1(first cycle of adjuvant treatment) and at the end of treatment visit (28 days after the last dose of treatment (up to 36 months)
Number of Species of bacteria and yeast composition
To investigate the microbiota composition changes during neoadjuvant therapy with nivolumab and ipilimumab and its relation to response and/or chemotoxicity. Number of Species of bacteria and yeast will be quantitfy and identify. Number of Change of composition will be investigate based on baseline samples compared to 12 weeks sample. DNA will be extracted from fecal samples taken prior to therapy and on-treatment (week 12). A gene sequencing approach will be utilized to survey microbial species in the gut in order to define microbiota as a function of the efficacy and safety.
Time frame: Baseline and at week 12