Localized Resectable Tumor Clinical Trial
Official title:
Immunotherapy in MSI/dMMR Tumors in Perioperative Setting.
This trial is a multicenter, 4-cohort, prospective, Phase II trial conducted in patients with untreated resectable MSI/dMMR carcinomas or EBV+ gastric cancer 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 endometrial, colorectal and gastric cancers to be the most frequent recruited and constructed our statistical hypothesis with results in those 3 cancers. However patients with other localized MSI/dMMR tumors could be included.
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). A single dose 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 pembrolizumab injection, as per standard practices. An adjuvant treatment will be administered upon the Investigator decision, depending on 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 160 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, leading to the inclusion of a maximum of 30 patients by cohort. 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. ;