MSI/dMMR tumors or EBV+ gastric cancer
Conditions
Sponsors
Centre Léon Bérard
Eligibility
Sex/Gender
All
Inclusion criteria
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: - Colorectal Cancer (cT3/T4 N0 M0 ou cT N+ M0 on thoraco-abdomino-pelvic TAP CT-scan and echo-endoscopy) OR - Oesogastric (gastric, gastro-oesophageal or oesophageal) cancer (cT2 to cT4, N, M0 on TAP CT-scan and echo-endoscopy) OR - Endometrial carcinoma (stage III) OR - Other tumor types (cT2 to cT4, N, M0 on TAP CT-scan and echo-endoscopy) : biliary tract or pancreas adenocarcinoma, small bowel adenocarcinoma (duodenum, jejunum, ileum), peritoneum adenocarcinoma. I3. MSI/dMMR established by immunohistochemistry (IHC) [MMR protein expression] and polymerase chain reaction (PCR) [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 among 5 microsatellite markers analyzed on PCR (BAT25, BAT26, NR21, NR24, and NR27) proves MSI/dMMR. OR EBV-positive gastric cancers. EBV positivity will be assessed by EBER (EBV-encoded small RNAs) in situ hybridization (ISH) (EBER-PNA EnVision flex probe (Dako)). The intensity of staining (weak, moderate or intense) and the percentage of positive cells will be recorded. Cases showing nuclear staining in at least 5% of tumI4. 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, platelets = 100 x 109, - Creatinine = 1.5 x ULN or calculated creatinine clearance ? 50 ml/min using either MDRD or CKD-EPI formula, (MDRD will be used for patients > 65 years) - AST and ALT = 3 x ULN, total bilirubin = 1.5 ULN (or direct bilirubin = ULN for participants with total bilirubin levels >1.5 × ULN), - INR or PT = 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. or cells will be considered positive for EBV infection. ...See the protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: E1. MSS/pMMR tumors. E2. Metastatic disease (stage IV). E3. HIV positive with CD4 count under 400 cells/mm3. E4. Active Hepatitis B virus (HBV), defined by a positive hepatitis B surface antigen [HBsAg] test prior to inclusion, or Hepatitis C virus (HCV) 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. ...See the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of pembrolizumab MK-3475 in perioperative setting in patients with untreated localized non-metastatic MSI/dMMR carcinomas, independently of their anatomical origin.;Secondary Objective: To evaluate: • The safety of the perioperative treatment according to NCI CTC-AE v5, • The post-operative morbidity according to modified Clavien Dindo scoring, • The R0 resection rate, • The major pathological response (= 10% residual viable tumor) rate • The recurrence-free survival (RFS) using RECIST 1.1, • The overall response rate (ORR) at 4 weeks after the injection of pre-operative pembrolizumab using RECIST 1.1, • The rate of second cancers in the Lynch syndrom spectrum, • The overall survival (OS), • The progression-free survival (PFS2) after recurrence, • The quality of life (QoL), • The prognostic value of lung immune prognostic index (LIPI).;Primary end point(s): The primary endpoint will be the rate of complete pathological response (pCR) after surgery. A complete pathological response will be defined as 0% viable tumor cells. ;Timepoint(s) of evaluation of this end point: Rate of complete pathological response (pCR) after surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Safety profile •Rate of surgical complications •Percentage of patients with R0 resection •Percentage of patients with major pathological response •RFS ...See the protocol;Timepoint(s) of evaluation of this end point: • 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. • Rate of surgical complications (post-operative morbidity) assessed according to modified Clavien Dindo scoring. • Percentage of patients with R0 resection. • Percentage of patients with major pathological response (= 10% residual viable tumor). • RFS, defined as the time from the date of first study treatment administration to the date of first documented recurrence (second cancer excluded). ...See the protocol | — |
Countries
France
Contacts
Public ContactDRCI
Centre Léon Bérard
Outcome results
None listed