- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03026140
Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (NICHE)
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)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Marieke van de Belt
- Phone Number: 1926 +3120512
- Email: m.vd.belt@nki.nl
Study Locations
-
-
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Amsterdam, Netherlands
- Recruiting
- OLVG
-
Contact:
- A van Lent
-
Amsterdam, Netherlands, 1066CX
- Recruiting
- Marieke van de Belt
-
Contact:
- Marieke van de Belt
- Phone Number: 1926 +3120512
- Email: m.vd.belt@nki.nl
-
Den Haag, Netherlands
- Not yet recruiting
- Haga ziekenhuis
-
Contact:
- T Aukema
-
Eindhoven, Netherlands
- Recruiting
- Catharina Ziekenhuis
-
Contact:
- P Burger
-
Haarlem, Netherlands
- Recruiting
- Spaarne Ziekenhuis
-
Contact:
- S Oosterling
-
Hilversum, Netherlands
- Not yet recruiting
- Tergooi
-
Contact:
- E. Hendriks
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- 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+
Exclusion criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: group 2
drug: 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)
|
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Names:
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)
Other Names:
|
Experimental: group 1
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
|
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Names:
|
Experimental: Anti-IL8 cohort 4 (pMMR/MSS tumors)
drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
|
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)
Other Names:
|
Experimental: Relatlimab cohort 5 (pMMR/MSS tumors)
drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
|
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
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
Other Names:
|
Experimental: Relatlimab cohort 6 (dMMR/MSI tumors)
drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
|
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events during the treatment and follow-up (safety)
Time Frame: until 100 days after last patient last study drug treatment
|
Adverse events will be assessed (according to CTCAE v4.0) during treatment and follow-up.
|
until 100 days after last patient last study drug treatment
|
Disease free survival
Time Frame: until 5 years after diagnosis
|
To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival
|
until 5 years after diagnosis
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immune activating capacity of short-term pre-operative immunotherapy
Time Frame: within 2 years after study completion
|
identify underlying potential escape mechanisms by comparing pre-treatment and post-treatment biopsies
|
within 2 years after study completion
|
Relapse free survival
Time Frame: 3-5 years after last patient inclusion.
|
3-5 years after last patient inclusion.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Myriam Chalabi, MD, Antoni van Leeuwenhoek
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Cyclooxygenase 2 Inhibitors
- Nivolumab
- Celecoxib
- Ipilimumab
Other Study ID Numbers
- N16NCI
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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