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Colon CarcinomaPhase 2NICHENCT03026140

Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer

A Phase 2 study testing Nivolumab, Ipilimumab and Celecoxib 200mg in people with Colon Carcinoma, run by The Netherlands Cancer Institute at 6 sites in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

In this exploratory study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy + novel IO combinations (i.e. anti-IL 8, COX2-inhibitors, anti-LAG3). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Carcinoma
What is being tested?
Nivolumab, Ipilimumab and Celecoxib 200mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
353 participants
Where
6 sitesNetherlands
Study dates
29 Mar 2017to 1 Mar 2032
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

  • Signed written informed consent
  • Patients at least 18 years of age
  • Non-metastatic adenocarcinoma of the colon (and rectosigmoid considered as nonrectal and not undergoing neoadjuvant treatment)
  • No signs of distant metastases on CT-scan and physical examination;
  • dMMR cohorts 3+6: >cT3 and/or N+

Who cannot join

  • No signs of distant metastases
  • No signs of obstruction or macroscopic bleeding or suspicion of perforation
  • Colonoscopy must be performed after registration to obtain study-specific biopsies. If biopsies are not possible, patients cannot be included in the study
  • WHO performance status of 0 or 1
  • No previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1
  • For patients with MSS tumors: no current use of NSAIDs or COX2-inhibitors at registration and no active peptic ulcer, gastrointestinal bleeding, unstable ischemic heart disease of thrombus etiology or significant established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease
Show all 13Show fewer
  • No radiotherapy prior to or planned post-surgery radiotherapy
  • No history of allergy to study drug components, severe hypersensitivity reaction to any monoclonal antibody, allergy or severe hypersensitivity to NSAIDs or COX2-I (MSS tumors)
  • No intercurrent illnesses, including but not limited to infections, unstable angina pectoris
  • No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
  • No autoimmune disease
  • No conditions requiring systemic treatment with either corticosteroids (10 mg daily prednisone or more and equivalents) or other immunosuppressive medications within 14 days of study drug administration
  • No live vaccines in the 4 weeks prior to inclusion

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Marieke van de Belt contact

+3120512 ext. 1926

m.vd.belt@nki.nl

6 sites in 1 country

Netherlands6 sites, 6 recruiting

  • Marieke van de Belt

    Amsterdam, 1066CX

    Marieke van de Belt, +3120512 ext. 1926, m.vd.belt@nki.nl

    Recruiting

  • OLVG

    Amsterdam

    A van Lent

    Recruiting

  • Catharina Ziekenhuis

    Eindhoven

    P Burger

    Recruiting

  • Spaarne Ziekenhuis

    Haarlem

    S Oosterling

    Recruiting

  • Tergooi

    Hilversum

    E. Hendriks

    Not yet recruiting

  • Haga ziekenhuis

    The Hague

    T Aukema

    Not yet recruiting

Other trials in Netherlands

About this study

Official title: Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (Amended Protocol of: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity: The NICHE TRIAL)

In this exploratory study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy + novel IO combinations (i.e. anti-IL 8, COX2-inhibitors, anti-LAG3). This treatment will be given during the window period until surgical resection of the tumor. The duration of treatment will be in between approximately 6 and 12 weeks.

Read the detailed description

In this multi-center, open-label, exploratory study, the investigators will enroll 60 patients within two years, including 30 patients with MSS tumors and 30 patients with MSI tumors. Patients with MSS tumors will be randomized to either group 1 or 2. Patients with MSI tumors will all be allocated to group 1.

Patients in group 1 will be treated with a single dose of ipilimumab 1mg/kg on day 1 and two cycles of nivolumab 3mg/kg on day 1 and 15, respectively.

Patients in group 2 will be treated with a single dose of ipilimumab 1mg/kg on day 1, two cycles of nivolumab 3mg/kg one day 1 and 15 and celecoxib daily until the day before surgery.

The study was amended in May 2020 to enroll an additional 70 patients in the MSI cohort after the first 30 patients, making a total of 100 patients with MSI tumors. A formal sample size calculation and primary endpoint of 3-year disease-free-survival (DFS) for this group was added.

The study was amended in July 2021 to add a new cohort, cohort 4, for patients with pMMR/MSS tumors. Once accrual of 30 evaluable patients in group 2 was completed, a new cohort opened in which patients will receive nivolumab plus anti-IL8 (BMS-986253).

The study was amended in November 2022 to add cohort 5 and 6, both in which patients will receive nivolumab plus relatlimab (anti-LAG3). Patients with pMMR/MSS tumors will be randomized 1:1 between cohort 4 and cohort 5, patients with dMMR/MSI tumors will be enrolled in cohort 6.

Accrual for cohort 4 was reached in July 2023. In April 2024, accrual for cohort 6 was reached. Per April 2024 only cohort 5 is open for recruitment.

The study was amended in April 2025 to add cohort 7 and 8. Patients with dMMR/MSI tumors will be randomized 1:1 between cohort 7 and 8, in which they will receive 3 cycles of nivolumab + relatlimab or 3 cycles of nivolumab monotherapy respectively. Per June 2025, cohort 5, 7 and 8 are open for recruitment.

Accrual was reached for cohort 8 in February 2026. As February 2026 only cohorts 5 and 7 are open for recruitment. This also means that patients with dMMR/MSI tumors will no longer be randomized but automatically be registered in cohort 7 (and receive 3 cycles of nivolumab + relatlimab).

Conditions
Colon Carcinoma
Being tested
Nivolumab, Ipilimumab, Celecoxib 200mg, BMS-986253, Relatlimab (BMS-986016)
Keywords
MSI tumors, MSS tumors, short-term immunotherapy, surgical resection, nivolumab, ipilimumab, COX2, Anti-IL8, Relatlimab, Anti-LAG3
Medical subject headings
Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called nivolumab (opdivo)

    Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery

  • IpilimumabDrug

    Also called Ipilimumab (Yervoy)

    Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery

  • Celecoxib 200mgDrug

    Also called Celebrex

    celecoxib will be administered starting day 1 until 1 day before surgery daily (if patient is randomized to group 2 (only applicable for patients with a MSS tumor)

  • BMS-986253Drug

    Also called Anti-IL8

    BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)

  • Relatlimab (BMS-986016)Drug

    Also called Relatlimab

    Relatlimab will be administered IV, in cohort 5 240mg on day 1 and day 15, in cohort 6 480mg on day 1 and day 29, in cohort 7 160mg on day 1, day 29 and day 57

Study groups in NCT03026140
Study groupRoleWhat they receive
group 1 - closedExperimentaldrug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
Receives: Drug: Nivolumab; Drug: Ipilimumab
group 2 - closedExperimentaldrug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV) drug: celecoxib 200 mg daily (oral)
Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Celecoxib 200mg
Anti-IL8 cohort 4 (pMMR/MSS tumors) - closedExperimentaldrug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
Receives: Drug: Nivolumab; Drug: BMS-986253
Relatlimab cohort 5 (pMMR/MSS tumors)Experimentaldrug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
Receives: Drug: Nivolumab; Drug: Relatlimab (BMS-986016)
Relatlimab cohort 6 (dMMR/MSI tumors) - closedExperimentaldrug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
Receives: Drug: Nivolumab; Drug: Relatlimab (BMS-986016)
Cohort 7 - dMMR - 3 cycles neoadjuvant nivolumab + relatlimab - closedExperimentalPatients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) + relatlimab (160mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment
Receives: Drug: Nivolumab; Drug: Relatlimab (BMS-986016)
Cohort 8 - dMMR - 3 cycles neoadjuvant nivolumab - closedExperimentalPatients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment.
Receives: Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events during the treatment and follow-up (safety)

    Adverse events will be assessed (according to CTCAE v4.0) during treatment and follow-up.

    Measured: until 100 days after last patient last study drug treatment

  2. Disease free survival

    To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival

    Measured: until 5 years after diagnosis

  3. Major Pathological Response

    To assess efficacy of neoadjuvant nivolumab monotherapy and neoadjuvant nivolumab plus relatlimab in terms of major pathologic response

    Measured: From date of randomization until the date of first documented progression, assessed up to 63 months

Secondary outcomes (2)

  1. Immune activating capacity of short-term pre-operative immunotherapy

    identify underlying potential escape mechanisms by comparing pre-treatment and post-treatment biopsies

    Measured: within 2 years after study completion

  2. Relapse free survival

    Measured: 3-5 years after last patient inclusion.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2017 (estimated)
  2. Study start29 Mar 2017
  3. Primary completion1 Mar 2032 (estimated)
  4. Study completion1 Mar 2032 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
353 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03026140
Sponsor's protocol ID
N16NCI
Other IDs
2024-513314-35-00
Acronym
NICHE
Status last verified
Sep 2026
First submitted
15 Dec 2016
Last updated
30 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chalabi M, van den Dungen LDW, de Gooyer PGM, Balduzzi S, Aalbers AGJ, Kerver ED, Grootscholten C, Dokter S, Bloemen JG, Hendriks ER, Aukema TS, Oosterling SJ, Verbeek WHM, Voest EE, Kok NFM, Foppen MHG, Beets-Tan RG, Tin A, Jurdi A, Schumacher TN, van Leerdam ME, van den Berg JG, Haanen JBAG. Disease-free survival and overall survival after neoadjuvant immunotherapy in mismatch repair-deficient colon cancer in the Netherlands: results of the single-arm, multicentre, phase 2, NICHE-2 trial. Lancet. 2026 Oct 21:S0140-6736(26)01602-8. doi: 10.1016/S0140-6736(26)01602-8. Online ahead of print.

    PubMed 42906564

  • Tan PB, Verschoor YL, van den Berg JG, Balduzzi S, Kok NFM, Ijsselsteijn ME, Moore K, Jurdi A, Tin A, Kaptein P, van Leerdam ME, Haanen JBAG, Voest EE, de Miranda NFCC, Schumacher TN, Wessels LFA, Chalabi M. Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers. Nature. 2025 Dec;648(8094):726-735. doi: 10.1038/s41586-025-09679-4. Epub 2025 Oct 20.

    PubMed 41115454

  • de Gooyer PGM, Verschoor YL, van den Dungen LDW, Balduzzi S, Marsman HA, Geukes Foppen MH, Grootscholten C, Dokter S, den Hartog AG, Verbeek WHM, Woensdregt K, van den Broek JJ, Oosterling SJ, Schumacher TN, Kuhlmann KFD, Beets-Tan RGH, Haanen JBAG, van Leerdam ME, van den Berg JG, Chalabi M. Neoadjuvant nivolumab and relatlimab in locally advanced MMR-deficient colon cancer: a phase 2 trial. Nat Med. 2024 Nov;30(11):3284-3290. doi: 10.1038/s41591-024-03250-w. Epub 2024 Sep 15.

    PubMed 39278994

  • Cercek A. Neoadjuvant Treatment of Mismatch Repair-Deficient Colon Cancer - Clinically Meaningful? N Engl J Med. 2024 Jun 6;390(21):2024-2025. doi: 10.1056/NEJMe2404601. No abstract available.

    PubMed 38838316

  • Chalabi M, Verschoor YL, Tan PB, Balduzzi S, Van Lent AU, Grootscholten C, Dokter S, Buller NV, Grotenhuis BA, Kuhlmann K, Burger JW, Huibregtse IL, Aukema TS, Hendriks ER, Oosterling SJ, Snaebjornsson P, Voest EE, Wessels LF, Beets-Tan RG, Van Leerdam ME, Schumacher TN, van den Berg JG, Beets GL, Haanen JB. Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer. N Engl J Med. 2024 Jun 6;390(21):1949-1958. doi: 10.1056/NEJMoa2400634.

    PubMed 38838311

  • Wang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and Prostaglandins in Tumor Immunology and Microenvironment of Gastrointestinal Cancer. Gastroenterology. 2021 Dec;161(6):1813-1829. doi: 10.1053/j.gastro.2021.09.059. Epub 2021 Oct 2.

    PubMed 34606846

  • Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, Maas M, Mertz M, Veninga V, Bounova G, Broeks A, Beets-Tan RG, de Wijkerslooth TR, van Lent AU, Marsman HA, Nuijten E, Kok NF, Kuiper M, Verbeek WH, Kok M, Van Leerdam ME, Schumacher TN, Voest EE, Haanen JB. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020 Apr;26(4):566-576. doi: 10.1038/s41591-020-0805-8. Epub 2020 Apr 6.

    PubMed 32251400

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Ipilimumab and Celecoxib 200mg in people with Colon Carcinoma, run by The Netherlands Cancer Institute at 6 sites in Netherlands.

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 5 inclusion and 13 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 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Netherlands. 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 Marieke van de Belt (+3120512 ext. 1926, m.vd.belt@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events during the treatment and follow-up (safety) (time frame: until 100 days after last patient last study drug treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03026140, which also lists 7 linked publications.

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 30 Sep 2026.

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