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

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.

Study Overview

• Status: Recruiting
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: Pegasys; Drug: Saline

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ismail Gögenur, MD, Professor; Phone Number: 0045 26356426; Email: igo@regionsjaelland.dk
• Study Contact Backup: Name: Helin Yikilmaz Pardes, MD; Phone Number: 0045 28913473; Email: heyi@regionsjaelland.dk

Study Locations

• Denmark
  • Zealand
    • Herlev, Zealand, Denmark, 2730
      • Recruiting
      • Herlev University Hospital
      • Principal Investigator: Ismail Gögenur, MD, Professor
      • Contact: Helin Yikilmaz Pardes, MD; Phone Number: 0045 28913473; Email: heyi@regionsjaelland.dk
      • Sub-Investigator: Helin Yikilmaz Pardes, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; 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; 45 mikrograms of Pegasys. Two subcutanous doses will be administered with at least 7 days in between
Placebo Comparator: Placebo; 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; 0.50 ml of Saline. Two subcutanous doses will be administered with at least 7 days in between

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Zealand University Hospital
• Collaborators: University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 10, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2a
• Other Study ID Numbers: SJ-874

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No