Clinical trial NCT03370198: Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Colon Cancer Liver Metastasis
Lead sponsor: Celyad Oncology SA
Sponsor class: INDUSTRY
First posted: 2017-12-12
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

Brief 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). 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.


Eligibility 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.

Primary outcomes:
measure: The occurrence of DLTs until 14 days after the last NKR-2 study treatment administration (Visit Day 43)
timeFrame: From study treatment start (Day 1) till 14 days after the last NKR-2 study treatment administration (Day 43)
Secondary outcomes:
measure: The occurrence of AEs and SAEs during the study treatment until 30 days after the last study treatment administration (Visit Day 57)
timeFrame: From study treatment start (Day 1) till 30 days after the last study treatment administration (Day 57)
measure: The occurrence and duration of objective clinical response (complete response (CR), partial response (PR))
timeFrame: through study completion (up to month 24)
measure: The occurrence and duration of clinical benefit (complete response (CR), partial response (PR) and stable disease (SD))
timeFrame: through study completion (up to month 24)
measure: The occurrence and duration of mixed response (MR)
timeFrame: through study completion (up to month 24)
measure: The resection rate at Visits Day 57 and Month 3
timeFrame: At visits Day 57 and Month 3
measure: The progression-free survival (PFS)
timeFrame: through study completion (up to month 24)
measure: The event-free survival (EFS)
timeFrame: through study completion (up to month 24)
measure: The overall survival (OS).
timeFrame: through study completion (up to month 24)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
Study officials:
affiliation: Celyad Oncology SA
name: Frédéric Lehmann, MD
role: PRINCIPAL_INVESTIGATOR
References: