Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer
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)
The Netherlands Cancer Institute
353 participants
Mar 29, 2017
INTERVENTIONAL
Conditions
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). 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.
Eligibility
Inclusion Criteria5
- 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 Criteria13
- 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
Interventions
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
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-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)
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
Locations(6)
View Full Details on ClinicalTrials.gov
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NCT03026140