pMMR Colon cancer MedDRA version: 20.0 Level: PT Classification code 10009944 Term: Colon cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Pegylated Interfeon alfa 2a
Product Name: Pegylated Interferon alfa 2a
Pharmaceutical Form: Injection
INN or Proposed INN: PEGINTERFERON ALFA-2A
CAS Number: 198153-51-4
Other descriptive n
Sponsors
Zealand University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients above 18 years of age. 2. Patients diagnosed with pMMR colonic adenocarcinoma and scheduled for laparoscopic hemicolectomy. 3. ASA class I-III (Classification of the American Society of Anesthesiology) 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 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: • Patients with childbearing potential without a negative pregnancy test before initiating study drug and / or non-acceptance to the use of contraceptive methods * • ECOG score function> / = 3 • Current liver or renal disease. • Previous depression diagnosed by a psychiatrist or in treatment with antidepressant • Autoimmune disease. • Uncontrolled thyroid disease. • Patients who are or have recently (within 6 months) received treatment with immunosuppressive agents other than corticosteroid treatment. • Epilepsy and / or other serious CNS disorders. • Patients that have undergone major surgery within one month before planned colon resection. • Known hypersensitivity to recombinant interferon or auxiliary products of Pegasys®. * Spiral, pill, implant, transdermal patch, vaginal ring or depot injection. Sterile / infertile subjects are exempt from the use of contraception. To be considered sterile or infertile must generally be surgical sterilization (vasectomy, bilateral tubectomy, hysterectomy or ovariectomy) or be postmenopausal, defined as absent menstruation for at least 12 months prior to study enrolment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this study is to examine the effect of pre-operative Interferon-a2a administration on post-operative immune suppression and changes in the tumour microenvironment. We hypothesize, that interferon enhances pre-operative immune function, lowers post-operative immune paralysis and increases infiltration of lymphocytes in the local tumor microenvironment.;Secondary Objective: Patient reported outcome measures NanoString analysis cfDNA analysis ;Primary end point(s): The primary endpoint consists of two primary outcomes: • Differences in measures of lymphocytic subpopulations (FLOW) between intervention and placebo group, seen as a higher number of CD3, 4, 8 and HLA-positive cells in the intervention group, on the day before and the day after surgery. • Differences in tumor-infiltrating lymphocytes in the resected specimen at the tumor center and invasive margin between the intervention and placebo group. This will be analysed via immunohistochemistry with staining for CD3+, CD4+ and CD8+ T-cells. ;Timepoint(s) of evaluation of this end point: FLOW analysis: On blood samples the day before surgery versus blood samples the day after surgery Tumor-infiltrating lymphocyte analysis: On the resected specimen on the day of surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Differences in measures of Quality of recovery (QoR-15) between intervention and placebo group, seen as a higher mean QoR in intervention group on the third and 12-16 post-operative day. • Differences in key systemic immune responses in blood, between the intervention and placebo group on samples taken before first treatment and before surgery, analysed via a multiplex gene assay. The multiplex gene assays include pathways related to antigen presentation (MHC-I, MHC-II, CD3, CD4 and CD8 related pathways) and related to innate cytotoxic and inflammatory activity (NK cells, macrophages and neutrophils). • Differences in tumor microenvironment in the resected specimen, analysed via a multiplex gene assay, between the placebo and intervention group. The multiplex gene assays include pathways related to antigen presentation (MHC-I, MHC-II, CD3, CD4 and CD8 related pathways) and related to innate cytotoxic and inflammatory activity (NK cells, macrophages and neutrophils). • Differences in cfDNA on approximately day 7 and day 1 before surgery and day 2, 12-16 and 28-32 after surgery between the placebo and intervention group. • Intragroup differences in tumor microenvironment in the biopsy before surgery vs the resected specimen. • Differences in measures of standard blood samples between the two groups, seen as a lower inflammation-grade in the intervention group, on the day prior to surgery (lower CRP and neutrophil/leukocyte ratio). • Differences in cytokines and interleukins related to post-operative inflammation between placebo and intervention group, with lower measures of inflammatory cytokines on the day before and the day after surgery in the intervention group. ;Timepoint(s) of evaluation of this end point: Differences in QoR-15: Third and 12-16 postoperative day Multiplex gene assay of systemic immune response: Blood samples taken before first treatment and before surgery. Multiplex gene assay of tumor microenvironment: On the rese | — |
Countries
Denmark
Contacts
Public ContactCenter for Surgical Science
Center for Surgical Science, Department of Surgery, Zealand University Hospital
Outcome results
None listed