Status:
ACTIVE_NOT_RECRUITING
Immunotherapy in MSI/dMMR Tumors in Perioperative Setting.
Lead Sponsor:
Centre Leon Berard
Conditions:
Localized Resectable Tumor
MSI/dMMR
Eligibility:
All Genders
18+ years
Phase:
PHASE2
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...
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 dose...
Eligibility Criteria
Inclusion
- Inclusion criteria
- 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.
- I4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1 within 7 days prior to the inclusion.
- 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.
- I9. Signed and dated IRB/IE approved informed consent form.
- Non-inclusion criteria
- E1. MSS/pMMR tumors.
- E2. Metastatic disease (stage IV).
- E3. HIV positive with CD4 count under 400 cells/mm3
- E4.Concurrent active Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] positive and/or detectable HBV DNA) or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection).
- E5. Active systemic autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin) is not considered a form of systemic treatment and is allowed.
- E6. Interstitial lung disease.
- E7. Prior (non-infectious) pneumonitis requiring systemic corticosteroid therapy or current pneumonitis.
- E8. History of severe hypersensitivity to another monoclonal antibody.
- E9. Receiving immunosuppressive therapy or having received corticosteroids (in dosing exceeding 10 mg daily of prednisone equivalent) within the last 2 months before inclusion.
- E10. Active infections.
- E11. Radiotherapy within the 2 weeks before inclusion. Patients must have recovered from all radiation related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease. - Not applicable
- E12. Live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- E13. Known history of active TB (Bacillus Tuberculosis).
- E14. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- E15. Pregnant or breastfeeding woman or patient expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 4 months after the last dose of study treatment.
- E16. Patient requiring tutorship or curatorship.
- E17. Ongoing anti-cancer treatment for another cancer (to be discussed with the coordinator in case of hormone therapy).
- E18. Prior history of other malignancies (except for HNPCC or Lynch syndrome-related cancers) unless the subjects has been free of the disease for at least 2 years.
- E19. Patient hospitalized at the moment of inclusion and treatment initiation (palliative care unit, retirement home … are considered as hospitals).
- E20. Recent hemorrhage (in the month before inclusion).
Exclusion
Key Trial Info
Start Date :
October 18 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 1 2029
Estimated Enrollment :
240 Patients enrolled
Trial Details
Trial ID
NCT04795661
Start Date
October 18 2021
End Date
October 1 2029
Last Update
January 7 2026
Active Locations (18)
Enter a location and click search to find clinical trials sorted by distance.
1
CHU Amiens Picardie
Amiens, France, 80054
2
CHU Clermont-Ferrand
Clermont-Ferrand, France, 63003
3
Centre Georges-Francois Leclerc
Dijon, France, 21079
4
Hopital Huriez
Lille, France, 59037