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Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer (LINK)

This study is currently recruiting participants.
Verified October 2017 by Celyad (formerly named Cardio3 BioSciences)
Sponsor:
ClinicalTrials.gov Identifier:
NCT03370198
First Posted: December 12, 2017
Last Update Posted: December 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Celyad (formerly named Cardio3 BioSciences)
  Purpose
The purpose of this study is to test an experimental anti-cancer immunotherapy called NKR-2 (modified T cells), to treat colorectal cancer with unresectable liver metastases. The trial will test three dose levels (dose escalation). At each dose, the patients will receive three successive hepatic transarterial administrations, two weeks apart, of NKR-2 cells. The study will enroll up to 18 patients.

Condition Intervention Phase
Colon Cancer Liver Metastasis Biological: NKR-2 cells Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
There will be a hepatic transarterial administration of NKR-2 every 2 weeks for a total of 3 administrations within 4 weeks (28 days). Three dose-level will be assessed (dose escalation with 3 dose-levels or 3 cohorts).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Celyad (formerly named Cardio3 BioSciences):

Primary Outcome Measures:
  • The occurrence of DLTs until 14 days after the last NKR-2 study treatment administration (Visit Day 43) [ Time Frame: From study treatment start (Day 1) till 14 days after the last NKR-2 study treatment administration (Day 43) ]
    A DLT is defined as any Grade 3 or higher toxicity and any Grade 2 or higher autoimmune toxicity


Secondary Outcome Measures:
  • The occurrence of AEs and SAEs during the study treatment until 30 days after the last study treatment administration (Visit Day 57) [ Time Frame: From study treatment start (Day 1) till 30 days after the last study treatment administration (Day 57) ]
    AEs and SAEs collection

  • The occurrence and duration of objective clinical response (complete response (CR), partial response (PR)) [ Time Frame: through study completion (up to month 24) ]
    Complete response (CR), partial response (PR)

  • The occurrence and duration of clinical benefit (complete response (CR), partial response (PR) and stable disease (SD)) [ Time Frame: through study completion (up to month 24) ]
    Complete response (CR), partial response (PR) and stable disease (SD)

  • The occurrence and duration of mixed response (MR) [ Time Frame: through study completion (up to month 24) ]
    The different types of MR are defined according to the following criteria: at least 30% decrease in the longest diameter (or shortest diameter for nodal lesions) occurring in at least one target lesion recorded and measured at baseline. Such response occurring in otherwise SD or PD status of the sum of diameters of target lesions and without the appearance of one or more new lesions will be classified as "MR (SD)", which corresponds to a SD with target lesion regression or "MR (PD)", which corresponds to PD with target lesion regression and, the appearance of new lesion(s) in otherwise PR status of the sum of diameters of target lesions will be classified as "MR (PR)", which corresponds to a PR with new lesion.

  • The resection rate at Visits Day 57 and Month 3 [ Time Frame: At visits Day 57 and Month 3 ]
    Assessment of R0, R1 and R2 resections

  • The progression-free survival (PFS) [ Time Frame: through study completion (up to month 24) ]
    The progression-free survival (PFS) is defined from registration in the study to the disease progression or death from any cause

  • The event-free survival (EFS) [ Time Frame: through study completion (up to month 24) ]
    The event-free survival (EFS) is defined as the time from registration in the study to any of the following events: progression, local or distant recurrence, or death from any cause

  • The overall survival (OS). [ Time Frame: through study completion (up to month 24) ]
    The overall survival (OS) is defined as the time from registration in the study to death. If death does not occur before the patient's last study visit, then the survival will be censored at the date when patient is known to be alive


Estimated Enrollment: 18
Actual Study Start Date: October 11, 2017
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose-level 1
The dose-level 1 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)
Biological: NKR-2 cells
NKR-2 cells will be administered (hepatic transarterial administration) every 2 weeks (14 days) for a total of 3 administrations within 4 weeks (28 days)
Other Name: NKG2D CAR-T cells
Experimental: Dose-level 2
The dose-level 2 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)
Biological: NKR-2 cells
NKR-2 cells will be administered (hepatic transarterial administration) every 2 weeks (14 days) for a total of 3 administrations within 4 weeks (28 days)
Other Name: NKG2D CAR-T cells
Experimental: Dose-level 3
The dose-level 3 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)
Biological: NKR-2 cells
NKR-2 cells will be administered (hepatic transarterial administration) every 2 weeks (14 days) for a total of 3 administrations within 4 weeks (28 days)
Other Name: NKG2D CAR-T cells

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • The patient must be ≥ 18 years old at the time of signing the ICF.
  • The patient must have a histologically proven adenocarcinoma of the colon or rectum.
  • The patient must have liver metastases non treatable with curative intent by surgical resection or local ablation at the time of registration.
  • The patient must have measurable hepatic metastases defined by RECIST version 1.1 for solid tumors.
  • The patient must have received one prior chemotherapy line for metastatic disease and have developed resistance or intolerance to this treatment.
  • The patient must have an ECOG performance status 0 or 1.
  • The patient must have the bone marrow reserve, hepatic and renal functions

Exclusion Criteria:

  • Patients who are presenting evidence of ascites, cirrhosis, portal hypertension, main portal venous tumor involvement or thrombosis as determined by clinical or radiologic assessment.
  • Patients who are planned to receive or concurrently receiving any non-cancer-directed investigational agent, or have received a non-cancer directed investigational agent within 3 weeks before the planned day for the first NKR-2 administration.
  • Patients who are scheduled to receive concurrent growth factor (except erythropoietin), systemic steroid, other immunosuppressive therapy or cytotoxic agents (systemic or localized) other than the treatment authorized per protocol.
  • Patients who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration.
  • Patients who have received a live vaccine ≤ 6 weeks prior to the planned day for the first NKR-2 administration.
  • Patients with a family history of congenital or hereditary immunodeficiency.
  • Patients with history of any autoimmune disease.
  Contacts and Locations
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): NCT03370198


Contacts
Contact: Luc Moriau, PhD +32 (0)10 394100 LINK@celyad.com
Contact: Olivia Denis, Msc +32 (0)10 394100 LINK@celyad.com

Locations
Belgium
Institut Jules Bordet Recruiting
Brussels, Belgium, 1000
Contact: Michel Dubuisson    +32 (0)2 5413179    michel.dubuisson@bordet.be   
Principal Investigator: Alain Hendlisz, MD         
Sponsors and Collaborators
Celyad (formerly named Cardio3 BioSciences)
Investigators
Principal Investigator: Frédéric Lehmann, MD Celyad (formerly named Cardio3 BioSciences)
  More Information

Responsible Party: Celyad (formerly named Cardio3 BioSciences)
ClinicalTrials.gov Identifier: NCT03370198     History of Changes
Other Study ID Numbers: CYAD-N2T-004
First Submitted: November 8, 2017
First Posted: December 12, 2017
Last Update Posted: December 12, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases