Effect of low-dose Interferon-alfa2a on perioperative immune suppression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Sjaelland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

28 Aug 2023 → ongoing

Decision date (initial)

2024-09-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517619-65-00

EudraCT number

2020-004567-11

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

1. 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 of and the day after surgery.

2. 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.

Secondary objectives 1

1. • 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. • Differences in phenotype and clonality of tumor-infiltrating and circulating T cells between placebo and intervention group, analyzed via combined single-cell transcriptome and TCR sequencing.

Conditions and MedDRA coding

Colon cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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)

Exclusion criteria 1

1. • 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • 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 of 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.

Secondary endpoints 1

1. A few of them: 1)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. 2) Differences in phenotype and clonality of tumor-infiltrating and circulating T cells between placebo and intervention group, analyzed via combined single-cell transcriptome and TCR sequencing. 3) Differences in tumor microenvironment in the resected specimen.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Sjaelland

Sponsor organisation

Region Sjaelland

Address

Lykkebaekvej 1

City

Koege

Postcode

4600

Country

Denmark

Scientific contact point

Organisation

Region Sjaelland

Contact name

Ismail Gögenur

Public contact point

Organisation

Region Sjaelland

Contact name

Ismail Gögenur

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications