Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (NICHE)
Colon Carcinoma
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
Experimental
Experimental
Experimental
Experimental
Experimental
group 1
group 2
Anti-IL8 cohort 4 (pMMR/MSS tumors)
Relatlimab cohort 5 (pMMR/MSS tumors)
Relatlimab cohort 6 (dMMR/MSI tumors)
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