NICHE: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity
Study Details
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 + 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
In this single-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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: group 1 drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV) |
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
Drug: Ipilimumab
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Names:
|
| 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) |
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
Drug: Ipilimumab
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Names:
Drug: Celecoxib 200mg
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:
|
Outcome Measures
Primary Outcome Measures
- Incidence of adverse events during the treatment and follow-up (safety) [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.
Secondary Outcome Measures
- Immune activating capacity of short-term pre-operative immunotherapy [within 2 years after study completion]
identify underlying potential escape mechanisms by comparing pre-treatment and post-treatment biopsies
- Relapse free survival [3-5 years after last patient inclusion.]
Eligibility Criteria
Criteria
Inclusion criteria:
-
Signed written informed consent
-
Patients at least 18 years of age
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Stage 1-3 adenocarcinoma of the colon
Exclusion criteria:
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No signs of distant metastases
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No signs of obstruction or macroscopic bleeding or suspicion of perforation
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Colonoscopy must be performed after registration to obtain study-specific biopsies. If biopsies are not possible, patients cannot be included in the study
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WHO performance status of 0 or 1
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No previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1
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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)
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Marieke van de Belt | Amsterdam | Netherlands | 1066CX | |
| 2 | OLVG | Amsterdam | Netherlands | ||
| 3 | Haga ziekenhuis | Den Haag | Netherlands | ||
| 4 | Catharina Ziekenhuis | Eindhoven | Netherlands | ||
| 5 | Spaarne Ziekenhuis | Haarlem | Netherlands | ||
| 6 | Tergooi | Hilversum | Netherlands |
Sponsors and Collaborators
- The Netherlands Cancer Institute
- Bristol-Myers Squibb
Investigators
- Principal Investigator: Myriam Chalabi, MD, Antoni van Leeuwenhoek
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- N16NCI