Ignite Creation Date:
2025-12-24 @ 12:58 PM
Ignite Modification Date:
2026-02-25 @ 12:53 AM
Study NCT ID:
NCT04795661
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-02-27
First Post:
2021-03-11
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Immunotherapy in MSI/dMMR Tumors in Perioperative Setting.
Sponsor:
Centre Leon Berard
Organization:
Study Overview
Official Title:
Immunotherapy in MSI/dMMR Tumors in Perioperative Setting.
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMHOTEP
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.
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: