Effect of Low-dose Interferon-alfa2a on Peri-operative Immune Suppression

Study Overview
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Brief Summary
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The aim of this randomized double-blinded placebo-controlled phase 2 study is to determine efficacy of preoperative treatment with interferon-alfa2a in patients with pMMR colon cancer on perioperative immune suppression and infiltration of lymphocytes in the primary tumor.

Official Title
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Effect of Low-dose Interferon-alfa2a on Peri-operative Immune Suppression

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: Pegasys
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients above 18 years of age. Patients diagnosed with pMMR colonic adenocarcinoma and scheduled for laparoscopic hemicolectomy. ASA class I-III (Classification of the American Society of Anesthesiology) 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. Severe heart 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blinded placebo-controlled phase 2 study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>Two 45 mikrogram doses of interferon-alfa2a (Pegasys). Both will be applied subcutanously. First dose is at least one week before surgery. Second dose on the day of surgery before the procedure. | Drug: Pegasys<br>* 45 mikrograms of Pegasys. Two subcutanous doses will be administered with at least 7 days in between<br>|
| Placebo Comparator: Placebo<br>Two 1 ml doses of saline liquid. Both will be applied subcutanously. First dose is at least one week before surgery. Second dose on the day of surgery before the procedure. | Drug: Saline<br>* 0.50 ml of Saline. Two subcutanous doses will be administered with at least 7 days in between<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow-analysis of lymphocytic subpopulations in blood | Change in CD3, CD4, and CD8 between intervention and placebo groups | Change between day of surgery (day 7-14 after first treatment) and postoperative day 1. | 
| T-cell infiltration in tumor | Difference in CD3, CD4 and CD8 T-cell infiltration between intervention and placebo groups | Day of surgery (day 7-14 after first treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of recovery (QoR-15) | Difference in QoR-15 between intervention and placebo groups | Third postoperative day and postoperative day 12-16 | 
| Multiplex gene assay - NanoString Pan Cancer 360 IO panel analysis in blood and resected tumor | Difference in gene expressions between intervention and placebo groups | Day of first treatment (Day 0) and day of surgery (day 7-14 after first treatment) | 
| cfDNA analysis in blood | Difference between intervention and placebo groups | Day of first treatment (Day 0), day of surgery (day 7-14 after first treatment), postoperative day 2, postoperative day 12-16, and postoperative day 28-32. | 
| Multiplex gene assay - NanoString Pan Cancer 360 IO panel analysis of tumor biopsy and resected specimen | Difference in gene expressions in tumor biopsies and resected specimen between intervention and placebo groups | Day of standard endoscopic biopsy (Day -7-14 before treatment) and day of surgery (day 7-14 after first treatment) | 
| CRP and neutrophil/lymphocyte ratio | Difference in CRP and neutrophil/lymphocyte ratio between intervention and placebo groups | Day of surgery (day 7-14 after first treatment) | 
| Immunological and inflammatory cytokines and interleukins | Difference between intervention and placebo groups | Day of surgery (day 7-14 after first treatment) and postoperative day 1. |