E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Colon cancer with proficient mismatch repair system |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009944 |
E.1.2 | Term | Colon cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this study is to examine the effect of pre-operative Interferon-α2a 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. |
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E.2.2 | Secondary objectives of the trial |
Patient reported outcome measures NanoString analysis cfDNA analysis
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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)
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | 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. |
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E.5.2 | 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.
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E.5.2.1 | 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 resected specimen on the day of the surgery. cfDNA analysis: On blood samples taken before first treatment, before surgery, and day 2, 12-16 and 28-32 after surgery Intragroup differences in tumor microenvironment: Biopsies from index colonoscopy (3 weeks before surgery) and from the resected specimen.. Difference in standard blood samples: On blood samples taken before first treatment, before surgery, and day 2, 12-16 and 28-32 after surgery. Cytokines related to postoperative inflammation: On blood samples taken before and after surgery. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |