Colon Cancer Liver MetastasisPhase 1LINKNCT03370198
Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer
A Phase 1 study testing NKR-2 cells in people with Colon Cancer Liver Metastasis, run by Celyad Oncology SA at 1 site in Belgium.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer Liver Metastasis
- What is being tested?
- NKR-2 cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteBelgium
- Study dates
- 11 Oct 2017to 15 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Colon Cancer Liver Metastasis
- Being tested
- NKR-2 cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NKR-2 cellsBiological
Also called NKG2D CAR-T 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)
| Study group | Role | What they receive |
|---|---|---|
| Dose-level 1 | Experimental | 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) Receives: Biological: NKR-2 cells |
| Dose-level 2 | Experimental | 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) Receives: Biological: NKR-2 cells |
| Dose-level 3 | Experimental | 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) Receives: Biological: NKR-2 cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
The occurrence of DLTs until 14 days after the last NKR-2 study treatment administration (Visit Day 43)
A DLT is defined as any Grade 3 or higher toxicity and any Grade 2 or higher autoimmune toxicity
Measured: From study treatment start (Day 1) till 14 days after the last NKR-2 study treatment administration (Day 43)
Secondary outcomes (8)
The occurrence of AEs and SAEs during the study treatment until 30 days after the last study treatment administration (Visit Day 57)
AEs and SAEs collection
Measured: From study treatment start (Day 1) till 30 days after the last study treatment administration (Day 57)
The occurrence and duration of objective clinical response (complete response (CR), partial response (PR))
Complete response (CR), partial response (PR)
Measured: through study completion (up to month 24)
The occurrence and duration of clinical benefit (complete response (CR), partial response (PR) and stable disease (SD))
Complete response (CR), partial response (PR) and stable disease (SD)
Measured: through study completion (up to month 24)
The occurrence and duration of mixed response (MR)
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.
Measured: through study completion (up to month 24)
The resection rate at Visits Day 57 and Month 3
Assessment of R0, R1 and R2 resections
Measured: At visits Day 57 and Month 3
The progression-free survival (PFS)
The progression-free survival (PFS) is defined from registration in the study to the disease progression or death from any cause
Measured: through study completion (up to month 24)
The event-free survival (EFS)
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
Measured: through study completion (up to month 24)
The overall survival (OS).
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
Measured: through study completion (up to month 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2017
- Study start11 Oct 2017
- Primary completion15 Jan 2018
- Study completion15 Dec 2018
Why it stopped: Difficulties in patient recruitment and clinical strategy modification based on new clinical data generated in the NKR-2 early development.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon Cancer Liver MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celyad Oncology SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frédéric Lehmann, MD, Principal investigator, Celyad Oncology SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03370198
- Sponsor's protocol ID
- CYAD-N2T-004
- Acronym
- LINK
- Status last verified
- Feb 2024
- First submitted
- 8 Nov 2017
- Last updated
- 28 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03370198
- Acronym / sponsor ID
- LINK / CYAD-N2T-004
- Conditions
- Colon Cancer Liver Metastasis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties in patient recruitment and clinical strategy modification based on new clinical data generated in the NKR-2 early development.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Celyad Oncology SAIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2017 (actual)
- Primary completion
- 15 Jan 2018 (actual)
- Study completion
- 15 Dec 2018 (actual)
- First posted
- 12 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- 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).
| Arm | Type | Receives |
|---|---|---|
| Dose-level 1 | Experimental | Biological: NKR-2 cellsThe 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) |
| Dose-level 2 | Experimental | Biological: NKR-2 cellsThe 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) |
| Dose-level 3 | Experimental | Biological: NKR-2 cellsThe 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NKR-2 cellsAlso: NKG2D CAR-T cellsNKR-2 cells will be administered (hepatic transarterial administration) every 2 weeks (14 days) for a total of 3 administrations within 4 weeks (28 days) | Biological | Dose-level 1, Dose-level 2, Dose-level 3 |
Primary outcome
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
8 secondary outcomes
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)
The occurrence and duration of objective clinical response (complete response (CR), partial response (PR))
Time frame: through study completion (up to month 24)
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)
The occurrence and duration of mixed response (MR)
Time frame: through study completion (up to month 24)
The resection rate at Visits Day 57 and Month 3
Time frame: At visits Day 57 and Month 3
The progression-free survival (PFS)
Time frame: through study completion (up to month 24)
The event-free survival (EFS)
Time frame: through study completion (up to month 24)
The overall survival (OS).
Time frame: through study completion (up to month 24)
Results and safety
The study was stopped early (reason given: Difficulties in patient recruitment and clinical strategy modification based on new clinical data generated in the NKR-2 early development.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frédéric Lehmann, MD principal investigator
Celyad Oncology SA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NKR-2 cells in people with Colon Cancer Liver Metastasis, run by Celyad Oncology SA at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulties in patient recruitment and clinical strategy modification based on new clinical data generated in the NKR-2 early development.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024; AzTrials last refreshed its copy on 8 Nov 2026.