Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (NICHE)

January 23, 2023 updated by: The Netherlands Cancer Institute

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)

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Anticipated)

268

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Amsterdam, Netherlands
        • Recruiting
        • OLVG
        • Contact:
          • A van Lent
      • Amsterdam, Netherlands, 1066CX
        • Recruiting
        • Marieke van de Belt
        • Contact:
      • Den Haag, Netherlands
        • Not yet recruiting
        • Haga ziekenhuis
        • Contact:
          • T Aukema
      • Eindhoven, Netherlands
        • Recruiting
        • Catharina Ziekenhuis
        • Contact:
          • P Burger
      • Haarlem, Netherlands
        • Recruiting
        • Spaarne Ziekenhuis
        • Contact:
          • S Oosterling
      • Hilversum, Netherlands
        • Not yet recruiting
        • Tergooi
        • Contact:
          • E. Hendriks

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Names:
  • Ipilimumab (Yervoy)
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:
  • Celebrex
Experimental: group 1
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Names:
  • Ipilimumab (Yervoy)
Experimental: Anti-IL8 cohort 4 (pMMR/MSS tumors)
drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)
Other Names:
  • Anti-IL8
Experimental: Relatlimab cohort 5 (pMMR/MSS tumors)
drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
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
Other Names:
  • Relatlimab
Experimental: Relatlimab cohort 6 (dMMR/MSI tumors)
drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
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
Other Names:
  • Relatlimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
until 100 days after last patient last study drug treatment
Disease free survival
Time Frame: until 5 years after diagnosis
To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival
until 5 years after diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
within 2 years after study completion
Relapse free survival
Time Frame: 3-5 years after last patient inclusion.
3-5 years after last patient inclusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Myriam Chalabi, MD, Antoni van Leeuwenhoek

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2017

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

December 15, 2016

First Submitted That Met QC Criteria

January 19, 2017

First Posted (Estimate)

January 20, 2017

Study Record Updates

Last Update Posted (Estimate)

January 26, 2023

Last Update Submitted That Met QC Criteria

January 23, 2023

Last Verified

January 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Colon Carcinoma

Clinical Trials on Nivolumab

3
Subscribe