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Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity (NICHE)

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ClinicalTrials.gov Identifier: NCT03026140
Recruitment Status : Recruiting
First Posted : January 20, 2017
Last Update Posted : August 2, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
The Netherlands Cancer Institute

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
Colon Carcinoma Drug: Nivolumab Drug: Ipilimumab Drug: Celecoxib 200mg 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity: The NICHE TRIAL
Actual Study Start Date : March 29, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine


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 Name: nivolumab (opdivo)

Drug: Ipilimumab
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Name: Ipilimumab (Yervoy)

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 Name: nivolumab (opdivo)

Drug: Ipilimumab
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Name: Ipilimumab (Yervoy)

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 Name: Celebrex




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. Relapse free survival [ Time Frame: 3-5 years after last patient inclusion. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03026140


Contacts
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Contact: Elvira Nuijten, MSc +3120512 ext 2671 e.nuijten@nki.nl

Locations
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Netherlands
Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands, 1066CX
Contact: Elvira Nuijten, MSc    +3120512 ext 2671    e.nuijten@nki.nl   
OLVG Recruiting
Amsterdam, Netherlands
Contact: A van Lent         
Sponsors and Collaborators
The Netherlands Cancer Institute
Bristol-Myers Squibb
Investigators
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Principal Investigator: Myriam Chalabi, MD Antoni van Leeuwenhoek

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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT03026140     History of Changes
Other Study ID Numbers: N16NCI
First Posted: January 20, 2017    Key Record Dates
Last Update Posted: August 2, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The Netherlands Cancer Institute:
MSI tumors
MSS tumors
short-term immunotherapy
surgical resection
nivolumab
ipilimumab

Additional relevant MeSH terms:
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Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Nivolumab
Ipilimumab
Celecoxib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action