Immunotherapy in MSI/dMMR Tumors in Perioperative Setting.
- Conditions
- Localized Resectable TumorMSI/dMMR
- Interventions
- Registration Number
- NCT04795661
- Lead Sponsor
- Centre Leon Berard
- Brief Summary
This trial is a multicenter, 3-cohort, prospective, Phase II trial conducted in patients with untreated resectable MSI/dMMR carcinomas and aiming to evaluate the safety and the efficacy of ICI (immune checkpoint inhibitor) as neoadjuvant treatment in these patients.
We hypothesize that immune checkpoint inhibitors (ICPi) will benefit to MSI/dMMR tumors from the early stages, whatever their anatomical origin. We assume that this neoadjuvant treatment would improve the response rate, providing even high rate of pathological complete responses and prolong patients survival.
We anticipated colorectal and gastric cancers to be the most frequent recruited and constructed our statistical hypothesis with results in those 2 cancers. However patients with other localized MSI/dMMR tumors could be included.
- Detailed Description
TREATMENT PLAN:
Pre-operative pembrolizumab will be administered intravenously (IV) over 30 minutes at the dose of 400 mg according to recent summary of product characteristics (SPC). Until four doses will be administered 6 weeks before the planned surgery, as close as possible to inclusion, and whenever possible during standard visit (surgery, anesthesia or other).
Surgery will be performed during the 6th week after the last pembrolizumab injection, as per standard practices.
An adjuvant treatment will be administered upon the Investigator decision, depending on the protocol: the results and tolerance of pre-operative treatment and ability of the patient to receive the treatment regarding his general post-operative condition.
STATISTICAL ANALYSIS:
A total of 240 patients will be enrolled in this study
Sample size was thus evaluated by analogy with an A'Hern's single stage phase II design with P0=25%, P1=50% and 85% power.
A sequential Bayesian design will be used to allow continuous monitoring of the primary endpoint and update knowledge gradually.
For each cohort, interim analyses are planned after 6-week follow up of the first 10 patients (i.e. after surgery) and then every 10 patients.
Early stopping will be recommended if there is a high posterior probability (≥90%) given observed data that the rate of pathological response is lower than 50%.
DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING:
All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. Serious adverse event (SAE) and Adverse Event of Specific Interest (AESI) reporting will be also paper-based by e-mail and/or Fax.
The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 240
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort Colorectal cancer (CRC) Pembrolizumab Pembrolizumab prior to surgery Cohort Oesogastric cancer Pembrolizumab Pembrolizumab prior to surgery Cohort Other cancer Pembrolizumab Pembrolizumab prior to surgery
- Primary Outcome Measures
Name Time Method Rate of complete pathological response (pCR) after surgery 6 weeks after first injection A complete pathological response will be defined as 0% viable tumor cells.
- Secondary Outcome Measures
Name Time Method Quality of life (QoL) Baseline,cycle 2 and 4 before surgery and 5 months after the surgery QoL, assessed using the EORTC QLQ-C30
The prognostic value of lung immune prognostic index (LIPI) 60 months the progression free survival for patient without surgery 60 months PFS, defined from the date of first documented recurrence to the date of documented progression.
Rate of surgical complications (post-operative morbidity) 1 Month after sugery The rate of surgical complications (post-operative morbidity) will be assessed according to modified Clavien Dindo scoring
Safety of the perioperative treatment 60 Months (over the whole study) Safety profile, determined using the National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTC AE) grading scale version 5. Adverse events will be described by their intensity and severity
Recurrence-free survival (RFS) 60 Months RFS defined as the time from the date of first study treatment administration to the date of first documented recurrence
Overall response rate (ORR) at 4, 10, 16 and 21 weeks after the pembrolizumab initiation 4, 10, 16, 21 weeks after first study treatment injection Percentage of patients with objective response at week 4, 10, 16 and 21 (complete or partial response) after neoadjuvant pembrolizumab, according to RECIST v1.1.
Rate of second cancer in the Lynch syndrom spectrum 60 Months Percentage of patients with second cancer
Rate of patients with the R0 resection 60 Months Percentage of patients with the R0 resection
Major pathological response rate 60 Months Percentage of patients with major pathological response (≤ 10% residual viable tumor)
The overall survival (OS) From 60 months OS, defined from the date of first study treatment administration to the date of death due to any cause.
Progression-free survival (PFS) after recurrence 60 months PFS, defined from the date of first documented recurrence to the date of documented progression.
Trial Locations
- Locations (17)
Groupe Hospitalier Diaconesses Croix Saint-Simon
🇫🇷Paris, France
Centre Georges-Francois Leclerc
🇫🇷Dijon, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Hopital Huriez
🇫🇷Lille, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Institut mutualiste Montsouris
🇫🇷Paris, France
CHU Poitiers
🇫🇷Poitiers, France
Centre Eugène Marquis
🇫🇷Rennes, France
CHU Saint Etienne
🇫🇷Saint-Étienne, France
CHU Clermont-Ferrand
🇫🇷Clermont-Ferrand, France
CHU Amiens Picardie
🇫🇷Amiens, France
Centre Léon Bérard
🇫🇷Lyon, France
Institut du Cancer Val d'Aurelle
🇫🇷Montpellier, France
APHP Hôpital Saint-Louis
🇫🇷Paris, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
APHP - Hôpital Saint-Antoine
🇫🇷Paris, France
Institut de cancérologie Strasbourg Europe
🇫🇷Strasbourg, France