Immunotherapy in Patients With Early dMMR Rectal Cancer

NCT ID: NCT05732389

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2052-02-29

Brief Summary

The purpose of this investigator-initiated, multicenter phase II trial is to evaluate the efficacy and tolerability of nivolumab and ipilimumab in patients with stage 1-3 MSI/dMMR rectal cancer.

The primary objective is:

Number of patients with complete clinical response after one or two cycles of immunotherapy.

Patients will be treated with 1 or 2 cycles of combination immunotherapy:

Cycle 1: Nivolumab 3 mg/kg days 1 and 15 & ipilimumab 1 mg/kg day 1 Cycle 2: Nivolumab 3 mg/kg days 50 and 65 & ipilimumab 1 mg/kg day 50

Conditions

Cancer of Rectum

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

nivolumab + ipilimumab

Patients will be treated with 1 or 2 cycles of combination immunotherapy:

Cycle 1: Nivolumab 3 mg/kg days 1 and 15 & ipilimumab 1 mg/kg day 1 Cycle 2: Nivolumab 3 mg/kg days 50 and 65 & ipilimumab 1 mg/kg day 50

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Nivolumab is a highly selective fully humanized, IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1) (17). PD-1 is an inhibitory receptor expressed on the surface of T-cells, B cells, macrophages, and NK cells. Endogenous binding of PD-1 with one of its two ligands PD-L1 and PD-L2 results in production of an inhibitory signal which results in reduction of T-cell proliferation, cytokine production, and cytotoxic activity. This results in significant dampening of the immune response. Nivolumab acts to selectively block the receptor activation of PD-L1 and PD-L2, resulting in a release of PD-1 mediated inhibition of the immune response.

Ipilimumab

Intervention Type: DRUG

Ipilimumab is a fully humanized monoclonal anti-CTLA-4 antibody that acts as an antineoplastic ICI by selectively binding to cytotoxic T-lymphocyte-associated antigen 4, a molecule located on the surface of cytotoxic T-cells, suppressing the immune response (17). Ipilimumab blocks CTLA-4, leading to a continuously active immune response in malignant cells.

Interventions

Nivolumab

Nivolumab is a highly selective fully humanized, IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1) (17). PD-1 is an inhibitory receptor expressed on the surface of T-cells, B cells, macrophages, and NK cells. Endogenous binding of PD-1 with one of its two ligands PD-L1 and PD-L2 results in production of an inhibitory signal which results in reduction of T-cell proliferation, cytokine production, and cytotoxic activity. This results in significant dampening of the immune response. Nivolumab acts to selectively block the receptor activation of PD-L1 and PD-L2, resulting in a release of PD-1 mediated inhibition of the immune response.

Intervention Type: DRUG

Ipilimumab

Ipilimumab is a fully humanized monoclonal anti-CTLA-4 antibody that acts as an antineoplastic ICI by selectively binding to cytotoxic T-lymphocyte-associated antigen 4, a molecule located on the surface of cytotoxic T-cells, suppressing the immune response (17). Ipilimumab blocks CTLA-4, leading to a continuously active immune response in malignant cells.

Intervention Type: DRUG

Other Intervention Names

Opdivo; Yervoy

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years.
• Histologically verified non-metastatic rectal cancer stage 1-3.
• No indication for local therapy like TEM.
• Histologically verified dMMR or MSI.
• Performance status (WHO) of 0-1.
• No previous chemotherapy, radiotherapy or immunotherapy for colorectal cancer
• Adequate haematological function defined as neutrophils ≥ 1.5 x 109/l and platelets ≥ 100 x 109/l.
• Adequate organ function (bilirubin ≤ 1.5 x UNL (upper normal limit), GFR (may be calculated) > 30 ml/min.
• Women of childbearing potential must have been tested negative in a serum pregnancy test within five days prior to registration. Fertile patients must agree to use a highly effective method of birth control. (i.e., pregnancy rate of less than 1 % per year) (Appendix 1) during the study and for six months after the discontinuation of study medication.
• Has provided written informed consent prior to performance of any study procedure.
• Written informed consent must be obtained according to the local Ethics Committee requirements.

Exclusion Criteria

• Any other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.
• Concomitant use of systemic glucocorticoids more than the equivalent dose to tablet prednisolone 10 mg/day. Treatment with systemic glucocorticoids must end no later than two weeks before inclusion.
• Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
• Known allergy or intolerance to any of the drugs used (nivolumab and ipilimumab).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

Zealand University Hospital

OTHER

Sponsor Role: collaborator

Aalborg University Hospital

OTHER

Sponsor Role: collaborator

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

Bispebjerg Hospital

OTHER

Sponsor Role: collaborator

Herlev and Gentofte Hospital

OTHER

Sponsor Role: collaborator

Vejle Hospital

OTHER

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Line S Tarpgaard, MD, Phd

Role: PRINCIPAL_INVESTIGATOR

Department of Oncology, Odense University Hospital, Denmark

Locations

Aalborg University Hospital

Aalborg, , Denmark

Site Status: RECRUITING

Aarhus University Hospital

Aarhus, , Denmark

Site Status: RECRUITING

Rigshospitalet

Copenhagen, , Denmark

Site Status: RECRUITING

Department of Oncology, Odense University Hospital

Odense, , Denmark

Site Status: RECRUITING

Zealand University Hospital

Roskilde, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Julie Bach

Role: CONTACT

Julie.Kristina.Bach@rsyd.dk

30714320

Christian P Olsen, Phd

Role: CONTACT

Christian.pilely.olsen@rsyd.dk

24342488

Facility Contacts

laurids Ø Poulsen, MD

Role: primary

Claus L Andersen, MD

Role: primary

Vinicius Lima, MD

Role: primary

Line S Tarpgarrd, MD

Role: primary

line.tarpgaard@rsyd.dk

+45 6541 2921

Ismail Gögenur, MD

Role: primary

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

KFE nr. 22.20

Identifier Type: -

Identifier Source: org_study_id