Back to resultsNeoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (NICHE)
Primary Purpose
Colon Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Nivolumab
Ipilimumab
Celecoxib 200mg
BMS-986253
BMS-986016
Sponsored by
About this trial
This is an interventional treatment trial for Colon Carcinoma focused on measuring MSI tumors, MSS tumors, short-term immunotherapy, surgical resection, nivolumab, ipilimumab, COX2, Anti-IL8, Relatlimab, Anti-LAG3
Eligibility Criteria
Inclusion criteria:
- Signed written informed consent
- Patients at least 18 years of age
- Stage 1-3 adenocarcinoma of the colon
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 and no history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- 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
Sites / Locations
- Marieke van de BeltRecruiting
- OLVGRecruiting
- Haga ziekenhuis
- Catharina ZiekenhuisRecruiting
- Spaarne ZiekenhuisRecruiting
- Tergooi
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
group 1
group 2
Anti-IL8 cohort 4 (pMMR/MSS tumors)
Relatlimab cohort 5 (pMMR/MSS tumors)
Relatlimab cohort 6 (dMMR/MSI tumors)
Arm Description
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
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)
drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
Outcomes
Primary Outcome Measures
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.
Disease free survival
To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival
Secondary Outcome Measures
Immune activating capacity of short-term pre-operative immunotherapy
identify underlying potential escape mechanisms by comparing pre-treatment and post-treatment biopsies
Relapse free survival
Full Information
NCT ID
NCT03026140
First Posted
December 15, 2016
Last Updated
January 23, 2023
Sponsor
The Netherlands Cancer Institute
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03026140
Brief Title
Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer
Acronym
NICHE
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 29, 2017 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Netherlands Cancer Institute
Collaborators
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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). This treatment will be given during the window period until surgical resection of the tumor. The duration of treatment will be approximately 6 weeks.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Carcinoma
Keywords
MSI tumors, MSS tumors, short-term immunotherapy, surgical resection, nivolumab, ipilimumab, COX2, Anti-IL8, Relatlimab, Anti-LAG3
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
268 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
group 1
Arm Type
Experimental
Arm Description
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
Arm Title
group 2
Arm Type
Experimental
Arm Description
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)
Arm Title
Anti-IL8 cohort 4 (pMMR/MSS tumors)
Arm Type
Experimental
Arm Description
drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
Arm Title
Relatlimab cohort 5 (pMMR/MSS tumors)
Arm Type
Experimental
Arm Description
drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
Arm Title
Relatlimab cohort 6 (dMMR/MSI tumors)
Arm Type
Experimental
Arm Description
drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
nivolumab (opdivo)
Intervention Description
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Ipilimumab (Yervoy)
Intervention Description
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Intervention Type
Drug
Intervention Name(s)
Celecoxib 200mg
Other Intervention Name(s)
Celebrex
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
BMS-986253
Other Intervention Name(s)
Anti-IL8
Intervention Description
BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)
Intervention Type
Drug
Intervention Name(s)
BMS-986016
Other Intervention Name(s)
Relatlimab
Intervention Description
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
Primary Outcome Measure Information:
Title
Incidence of adverse events during the treatment and follow-up (safety)
Description
Adverse events will be assessed (according to CTCAE v4.0) during treatment and follow-up.
Time Frame
until 100 days after last patient last study drug treatment
Title
Disease free survival
Description
To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival
Time Frame
until 5 years after diagnosis
Secondary Outcome Measure Information:
Title
Immune activating capacity of short-term pre-operative immunotherapy
Description
identify underlying potential escape mechanisms by comparing pre-treatment and post-treatment biopsies
Time Frame
within 2 years after study completion
Title
Relapse free survival
Time Frame
3-5 years after last patient inclusion.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marieke van de Belt
Phone
+3120512
Ext
1926
Email
m.vd.belt@nki.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Myriam Chalabi, MD
Organizational Affiliation
Antoni van Leeuwenhoek
Official's Role
Principal Investigator
Facility Information:
Facility Name
Marieke van de Belt
City
Amsterdam
ZIP/Postal Code
1066CX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marieke van de Belt
Phone
+3120512
Ext
1926
Email
m.vd.belt@nki.nl
Facility Name
OLVG
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A van Lent
Facility Name
Haga ziekenhuis
City
Den Haag
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
T Aukema
Facility Name
Catharina Ziekenhuis
City
Eindhoven
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
P Burger
Facility Name
Spaarne Ziekenhuis
City
Haarlem
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S Oosterling
Facility Name
Tergooi
City
Hilversum
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
E. Hendriks
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34606846
Citation
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.
Results Reference
derived
PubMed Identifier
32251400
Citation
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.
Results Reference
derived
Learn more about this trial
Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer
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