Patients with early stage (stage I-III) dMMR colon cancer MedDRA version: 21.0 Level: LLT Classification code 10009951 Term: Colon cancer NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Keytruda®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Concentration unit: mg milligram(s)
Concentration type: up
Sponsors
Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Have histologically confirmed localized dMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colon carcinoma. • Have indication for elective curative intended surgery without neoadjuvant chemo-therapy. • Be = 18 years of age on the date of signing the informed consent. • Provide written informed consent prior to registration according to the local regula-tory requirements. • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Have adequate bone marrow function: o Hemoglobin = 6.2 mmol/L or = 10 g/dL o Absolute neutrophil count (ANC) = 1.5 × 109/L o Platelet count = 100 × 109/L Have adequate kidney function: o Glomerular filtration rate (GFR) = 60 mL/min or creatinine =1.5 X upper lim-it of normal (ULN) Have adequate liver function: o Total bilirubin = 1.5 × ULN o Alanine aminotransferase (ALT): 10–70 U/L for males and 10–45 U/L for fe-males or = 2.5 × ULN o Alkaline phosphatase: 35–105 U/L or = 2.5 × ULN 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 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 43
Exclusion criteria
Exclusion criteria: • Has any serious or uncontrolled medical disorder that, in the opinion of the investi-gator or treating physician, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results. • Has an autoimmune disorder (except thyroiditis with replacement therapy and type I diabetes mellitus). • Has received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody/drug specifically targeting the T-cell co-stimulation or checkpoint pathways. • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active chronic or acute Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected). • Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoim-mune disease. • Has a history of allergy to study drug components or a history of severe hypersensi-tivity reaction to any monoclonal antibody
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to evaluate the efficacy of neoadjuvant treatment with pembrolizumab before colonic resection in patients with early-stage (I-III) dMMR colon cancer. ;Secondary Objective: The secondary objectives include investigating the safety and tolerability of pembrolizumab administered before surgery and developing predictive biomarkers that can identify patients with a pathological complete response to pembrolizumab. ;Primary end point(s): •Number of patients with pathological complete response.;Timepoint(s) of evaluation of this end point: Evaluation after surgery with resection of the tumor. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety and tolerability of pembrolizumab administered before surgery. Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received pembrolizumab using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded. AEs will be analyzed including but not limited to all AEs, SAEs, fatal AEs, and laboratory changes. • Postoperative surgical complications determined by Clavien-Dindo classification system. • Number of patients with major pathological response to treatment, corresponding to Mandard tumor regression grade 1 (complete response) or 2 (near complete response). • Number of patients with clinical complete response • Overall survival. Defined as the time from inclusion to death due to any cause. • Disease-free survival. Defined as the time from inclusion to recurrence or death due to any cause. • Response evaluation at the pre-operative MDT meeting • Biomarker assessment including the comparison of immunological markers across pre- and post-treatment biopsies and sequential blood samples using nCounter and GeoMx platforms (NanoString technologies, USA). • Methylated circulating cell-free DNA (cfDNA) specific for colon cancer analyzed across sequential blood samples using the TriMeth test. ;Timepoint(s) of evaluation of this end point: Analyses on blood and tissue samples will be done in bulk, when the samples have been collected. | — |
Countries
Denmark
Contacts
Public ContactCenter for Surgical Science
Zealand University Hospital
Outcome results
None listed