NCT04795661

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P75+ for phase_2

Timeline
42mo left

Started Oct 2021

Longer than P75 for phase_2

Geographic Reach
1 country

18 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress57%
Oct 2021Oct 2029

First Submitted

Initial submission to the registry

March 11, 2021

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 12, 2021

Completed
7 months until next milestone

Study Start

First participant enrolled

October 18, 2021

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 5, 2023

Completed
6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2029

Expected
Last Updated

January 7, 2026

Status Verified

January 1, 2026

Enrollment Period

2 years

First QC Date

March 11, 2021

Last Update Submit

January 6, 2026

Conditions

Localized Resectable TumorMSI/dMMR

Keywords

OncologyMSI/dMMR statusPembrolizumabImmunotherapyPhase IINeoadjuvant treatment

Outcome Measures

Primary Outcomes (1)

  • Rate of complete pathological response (pCR) after surgery

    A complete pathological response will be defined as 0% viable tumor cells.

    6 weeks after first injection

Secondary Outcomes (12)

  • Safety of the perioperative treatment

    60 Months (over the whole study)

  • Rate of surgical complications (post-operative morbidity)

    1 Month after sugery

  • Rate of patients with the R0 resection

    60 Months

  • Major pathological response rate

    60 Months

  • Recurrence-free survival (RFS)

    60 Months

  • +7 more secondary outcomes

Study Arms (3)

Cohort Colorectal cancer (CRC)

EXPERIMENTAL

Pembrolizumab prior to surgery

Drug: Pembrolizumab

Cohort Oesogastric cancer

EXPERIMENTAL

Pembrolizumab prior to surgery

Drug: Pembrolizumab

Cohort Other cancer

EXPERIMENTAL

Pembrolizumab prior to surgery

Drug: Pembrolizumab

Interventions

PembrolizumabDRUG

Administered intravenous (IV)

Also known as: MK3475 - Keytruda®
Cohort Colorectal cancer (CRC)Cohort Oesogastric cancerCohort Other cancer

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • I1. Age ≥ 18 years on the day of signing informed consent.
  • I2. Histologically proven localized non-metastatic tumor included in one of the 4 cohorts:
  • Colon or rectal Cancer (cT3/T4 N0 M0 ou cT N+ M0) OR
  • Oesogastric (gastric, gastro-oesophageal or oesophageal) cancer (cT2 to cT4 N M0) OR
  • Other tumor types (cT2 to cT4 N M0): small bowel adenocarcinoma (duodenum, jejunum, ileum).
  • I3. MSI/dMMR established by immunohistochemistry (IHC) \[MMR protein expression\] and polymerase chain reaction (PCR) (or Next-Generation Sequencing (NGS)) \[both techniques are required\] and validated by coordinator's team.
  • MMR and/or MSI tumors will be assessed using IHC with four antibodies (anti-MLH1, anti-MSH2, anti-MSH6 and anti-PMS2) and PCR (pentaplex panel is recommended: BAT-25, BAT-26, NR-21, NR-24, and NR-27) prior to screening. Loss of MLH1 and PMS2 / or MSH2 and MSH6 / or MSH6 alone / or PMS2 alone protein staining by IHC indicates dMMR, and tumor with ≥ 2 unstable markers analyzed on PCR proves MSI/dMMR, NGS will be accepted instead of PCR analysis.
  • I5. Adequate bone-marrow, hepatic, and renal functions, within 10 days prior to the start of study treatment with:
  • Hemoglobin ≥ 9 g/dl or ≥ 5.6 mmol/l, neutrophils ≥ 1.0 x 109/l, platelets ≥ 100 x 109/l,
  • Creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 30 ml/min/1.73m² using either MDRD or CKD-EPI formula,
  • AST and ALT ≤ 3 x ULN, total bilirubin ≤ 1.5 ULN (or direct bilirubin ≤ ULN for patients with total bilirubin \>1.5 × ULN),
  • International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants.
  • I6. Covered by a medical/health insurance.
  • I7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • I8. Patients of childbearing potential accepting to use effective contraceptive measures or abstain from heterosexual activity, for the course of the study through 4 months after the last dose of pembrolizumab MK-3475 adjuvant treatment or 6 months after adjuvant chemotherapy or being surgically sterile. Refer to Appendix 1 for approved methods of contraception.
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

CHU Amiens Picardie

Amiens, 80054, France

Location

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

Centre Georges-Francois Leclerc

Dijon, 21079, France

Location

Hopital Huriez

Lille, 59037, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Institut du Cancer Val d'Aurelle

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

APHP Hôpital Saint-Louis

Paris, 75010, France

Location

Institut mutualiste Montsouris

Paris, 75014, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

APHP - Hôpital Saint-Antoine

Paris, 75571, France

Location

Groupe Hospitalier Diaconesses Croix Saint-Simon

Paris, 75571, France

Location

CHU Poitiers

Poitiers, 86021, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

CHU Saint Etienne

Saint-Etienne, 42270, France

Location

Centre Paul Strauss

Strasbourg, 67200, France

Location

Institut de cancérologie Strasbourg Europe

Strasbourg, 67200, France

Location

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 11, 2021

First Posted

March 12, 2021

Study Start

October 18, 2021

Primary Completion

October 5, 2023

Study Completion (Estimated)

October 1, 2029

Last Updated

January 7, 2026

Record last verified: 2026-01

Locations

FR(18)