Peri-operative Association of Immunotherapy (Pre-operative Association of Nivolumab and Ipilimumab, Post-operative Nivolumab Alone) in Localized Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR) Oeso-gastric Adenocarcinoma (NEONIPIGA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04006262|
Recruitment Status : Recruiting
First Posted : July 5, 2019
Last Update Posted : June 14, 2021
|Condition or disease||Intervention/treatment||Phase|
|Localized Oesogastric Adenocarcimona MSI and or dMMR||Drug: Nivolumab 10 MG/ML Drug: Ipilimumab 200 MG in 40 ML Injection||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Peri-operative Association of Immunotherapy (Pre-operative Association of Nivolumab and Ipilimumab, Post-operative Nivolumab Alone) in Localized Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR) Oeso-gastric Adenocarcinoma: An Open-label GERCOR Phase II Study|
|Actual Study Start Date :||October 23, 2019|
|Estimated Primary Completion Date :||June 2024|
|Estimated Study Completion Date :||June 2024|
Experimental: Experimental arm
Drug: Nivolumab 10 MG/ML
Drug: Ipilimumab 200 MG in 40 ML Injection
Neo-adjuvant treatment : 1mg/kg over 30 minutes every 6 cycles - 2 cycles
- Complete pathological response (cPRR) rate [ Time Frame: time point when the tumor is examined after the surgery (up to 30 months) ]
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
- Disease-free survival (DFS) [ Time Frame: Up to 36 months ]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.
- Overall Survival (OS) [ Time Frame: Up to 36 months ]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.
- Number of participants with treatment-related adverse events [ 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. ]Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0
- Analyze MSI status [ Time Frame: up to 36 months ]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
- Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in 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) ]Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in blood of dMMR tumors.
- Number of Species of bacteria and yeast composition [ Time Frame: Baseline and at week 12 ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04006262
|Contact: Thierry ANDRE, MDemail@example.com|
|Contact: Marie-Line GARCIA LARNICOL, MDfirstname.lastname@example.org|
|CHRU Jean Minjoz||Recruiting|
|Contact: Marine JARY, MD|
|Principal Investigator: Marine JARY, MD|
|Hôpital Henri Mondor||Recruiting|
|Contact: Christophe TOURNIGAND, MD|
|Principal Investigator: Christophe TOURNIGAND, MD|
|Institut Hospitalier Franco-Britannique||Recruiting|
|Contact: Benoist CHIBAUDEL, Md|
|Principal Investigator: Benoist CHIBAUDEL, MD|
|CHRU Lille||Not yet recruiting|
|Contact: Guillaume PIESSEN, MD|
|Principal Investigator: guillaume PIESSEN, MD|
|Centre Léon Bérard||Recruiting|
|Lyon, France, 69373|
|Contact: Clélia COUTZAC, MD|
|Hôpital Privé Jean Mermoz||Not yet recruiting|
|Contact: Léa CLAVEL, MD|
|Principal Investigator: Léa CLAVEL, MD|
|ICM Val d'Aurelle||Not yet recruiting|
|Contact: Antoine ADENIS, MD|
|Principal Investigator: Antoine ADENIS, MD|
|CHU Nantes||Not yet recruiting|
|Contact: Solange PECOUT, MD|
|Principal Investigator: Solange PECOUT, MD|
|Hôpital Européen Geroges Pompidou||Recruiting|
|Contact: Aziz ZANNAN, MD|
|Principal Investigator: Aziz ZANNAN, MD|
|Hôpital Saint Antoine||Recruiting|
|Contact: Thierry ANDRE, MD|
|Principal Investigator: Thierry ANDRE, MD|
|Hôpital Saint Louis||Recruiting|
|Contact: Thomas APARICIO, MD|
|Principal Investigator: Thomas APARICIO, MD|
|Institut Mutualiste Montsouris||Not yet recruiting|
|Contact: Christophe LOUVET, MD|
|Principal Investigator: Christophe LOUVET, MD|
|Contact: David TOUGERON, MD|
|Principal Investigator: David TOUGERON, MD|
|CHU Pontchaillou Rennes||Recruiting|
|Rennes, France, 35033|
|Contact: Astrid LIEVRE, MD|
|CHU Toulouse||Not yet recruiting|
|Contact: Rosine GUIMBAUD, MD|
|Principal Investigator: Rosine GUIMBAUD, MD|
|Principal Investigator:||Thierry ANDRE, MD||Hôpital Saint Antoine PARIS|