Cancer of RectumPhase 2RESET-RNCT05732389
Immunotherapy in Patients With Early dMMR Rectal Cancer
A Phase 2 study testing Nivolumab and Ipilimumab in people with Cancer of Rectum, run by Odense University Hospital at 5 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Rectum
- What is being tested?
- Nivolumab and Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 5 sitesDenmark
- Study dates
- 1 Feb 2023to Feb 2052
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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).
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Denmark5 sites, 5 recruiting
- Recruiting
Aalborg University Hospital
Aalborg, 9000
laurids Ø Poulsen, MD
- Recruiting
Aarhus University Hospital
Aarhus, 8200
Claus L Andersen, MD
- Recruiting
Rigshospitalet
Copenhagen, 2100
Vinicius Lima, MD
- Recruiting
Department of Oncology, Odense University Hospital
Odense, 5000
Line S Tarpgarrd, MD, +45 6541 2921, line.tarpgaard@rsyd.dk
Line S Tarpgarrd, MD
- Recruiting
Zealand University Hospital
Roskilde, 4000
Ismail Gögenur, MD
About this study
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
- Being tested
- Nivolumab, Ipilimumab
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
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.
IpilimumabDrug
Also called Yervoy
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.
| Study group | Role | What they receive |
|---|---|---|
| nivolumab + ipilimumab | Experimental | 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 Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete clinical response
Proportion of patients with complete clinical response Complete clinical response will be defined as no visible or palpable tumor examined by rectal exploration (if low tumors), endoscopy and MR-scan. Patients with definite but less than complete regression BUT with a representative biopsy without viable tumor cells will also be classified as cCR in this trial.
Measured: Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)
Secondary outcomes (7)
Complete biological response
Proportion of patients with complete biological response
Measured: Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)
12 months recurrence
Proportion of patients without any sign of recurrence after 12 months.
Measured: after 12 months
Respons rate
Response rate according to mrTRG.
Measured: after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)
Adverse events
Adverse events assessed by the investigator according to the definitions in NCI-CTC, version 5.0
Measured: after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)
Bio-marker predictive models for treatment response and survival.
Correlation between bio-markers (ctDNA and CEA) and outcome.
Measured: after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)
Quality of life (EORCT QLQ-C30)
Change in Quality of life (EORCT QLQ-C30)
Measured: after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)
Quality of life (EORCT QLQ-CR29)
Change in Quality of life (EORCT QLQ-CR29)
Measured: after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2023
- Study start1 Feb 2023
- Primary completionJul 2027 (estimated)
- Study completionFeb 2052 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer of RectumStudies of the same condition, open and under way.
- More trials run by Odense University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Zealand University Hospital, Aalborg University Hospital, Aarhus University Hospital, Bispebjerg Hospital, Herlev and Gentofte Hospital, Vejle Hospital
- Responsible party
- Sponsor
- Investigators
- Line S Tarpgaard, MD, Phd, Principal investigator, Department of Oncology, Odense University Hospital, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05732389
- Sponsor's protocol ID
- KFE nr. 22.20
- Acronym
- RESET-R
- Status last verified
- Jul 2025
- First submitted
- 17 Jan 2023
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy in Patients With Early dMMR Rectal Cancer
- ClinicalTrials.gov ID
- NCT05732389
- Acronym / sponsor ID
- RESET-R / KFE nr. 22.20
- Conditions
- Cancer of Rectum
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Zealand University Hospital, Aalborg University Hospital, Aarhus University Hospital, Bispebjerg Hospital, Herlev and Gentofte Hospital, Vejle Hospital
- Study start
- 1 Feb 2023 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Feb 2052 (estimated)
- First posted
- 17 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| nivolumab + ipilimumab | Experimental | Drug: Nivolumab, Drug: IpilimumabPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab 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. | Drug | nivolumab + ipilimumab |
| IpilimumabAlso: YervoyIpilimumab 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. | Drug | nivolumab + ipilimumab |
Primary outcome
Complete clinical response
Time frame: Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)
Proportion of patients with complete clinical response Complete clinical response will be defined as no visible or palpable tumor examined by rectal exploration (if low tumors), endoscopy and MR-scan. Patients with definite but less than complete regression BUT with a representative biopsy without viable tumor cells will also be classified as cCR in this trial.
7 secondary outcomes
Complete biological response
Time frame: Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)
12 months recurrence
Time frame: after 12 months
Respons rate
Time frame: after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)
Adverse events
Time frame: after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)
Bio-marker predictive models for treatment response and survival.
Time frame: after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)
Quality of life (EORCT QLQ-C30)
Time frame: after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)
Quality of life (EORCT QLQ-CR29)
Time frame: after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Line S Tarpgaard, MD, Phd principal investigator
Department of Oncology, Odense University Hospital, Denmark
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Ipilimumab in people with Cancer of Rectum, run by Odense University Hospital at 5 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julie Bach (30714320, Julie.Kristina.Bach@rsyd.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete clinical response (time frame: Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.