Clinical trial NCT03310008: Dose Escalation and Dose Expansion Phase I Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2 Administered Concurrently With FOLFOX in Colorectal Cancer With Potentially Resectable Liver Metastases
Official title: An Open-label, Phase I Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2, Administered Concurrently With the Neoadjuvant FOLFOX Treatment in Patients With Potentially Resectable Liver Metastases From Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Colon Cancer Liver Metastasis
Lead sponsor: Celyad Oncology SA
Sponsor class: INDUSTRY
First posted: 2017-10-16
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Biological: NKR-2 cells The intervention will consist of an infusion of NKR-2 cells administered concurrently to a standard chemotherapy every 2 weeks (14 days) for a total of 3 infusions within 4 weeks (28 days).

Other Name: NKG2D CAR-T cells
Primary purpose: TREATMENT

Brief summary: SHRINK (Standard cHemotherapy Regimen and Immunotherapy with NKR-2) is an open-label Phase I study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 cells administered concurrently with a standard chemotherapy treatment (FOLFOX) in potentially resectable liver metastases from colorectal cancer.

The trial will test three dose levels. At each dose, the patients will receive three successive administrations, two weeks apart, NKR-2 cells. The study will enroll up to 36 patients (dose escalation and expansion phases).


Eligibility criteria: Inclusion Criteria:

1. Men or women ≥ 18 years old at the time of signing the ICF
2. Patients with histologically proven colorectal adenocarcinoma with potentially resectable liver metastases,
3. No previous chemotherapy for metastatic CRC,
4. The patient is due to receive first-line metastatic chemotherapy regimen with FOLFOX as a neoadjuvant
5. The patient must have an ECOG performance status 0 or 1
6. The patient must have sufficient bone marrow reserve, hepatic and renal functions

Detailed disease specific criteria exist and can be discussed with contacts listed below

Exclusion Criteria:

1. Patients who have received another cancer therapy within 2 weeks before the planned day for the apheresis
2. Patients who receive or are planned to receive any other investigational product within the 3 weeks before the planned day for the first NKR-2 administration
3. Patients who are planned to receive concurrent growth factor, systemic steroid or other immunosuppressive therapy or cytotoxic agent, other than the treatment authorized per protocol
4. Patients who underwent major surgery within 4 weeks before the planned day for the first treatment
5. Patients with uncontrolled intercurrent illness or serious uncontrolled medical disorder
6. Patients who have received a live vaccine within 6 weeks prior to the planned day for the first NKR 2 administration
7. Patients with a family history of congenital or hereditary immunodeficiency
8. Patients with history of any autoimmune disease

Primary outcomes:
measure: The occurrence of Dose Limiting Toxicities (DLT) in all patients during the study treatment until 14 days after the first NKR-2 study treatment administration
timeFrame: up to resection (up to day 99 to day 126)
measure: The objective response rate (ORR) before resection as measured by RECIST (version 1.1)
timeFrame: up to resection (up to day 99 to day 126)
Secondary outcomes:
measure: The occurrence of AEs and SAEs and any toxicity corresponding to DLT definition during the study treatment until resection visit
timeFrame: up to resection (up to day 99 to day 126)
measure: The occurrence of surgery complications and the wound healing status until 60 days after resection visit
timeFrame: until 60 days after resection
measure: The clinical benefit rate (CBR) before resection
timeFrame: up to resection (up to day 99 to day 126)
measure: The occurrence of mixed response (MR) before resection
timeFrame: up to resection (up to day 99 to day 126)
measure: The resection rate
timeFrame: resection (day 99 to day 126)
measure: The occurrence of pathological response at surgery
timeFrame: resection (day 99 to day 126)
measure: The disease-free survival (DFS) or progression-free survival (PFS)
timeFrame: through study completion (up to month 28)
measure: The event-free survival (EFS)
timeFrame: through study completion (up to month 28)
measure: The overall survival (OS)
timeFrame: through study completion (up to month 28)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: Celyad Oncology SA
name: Frédéric Lehmann, MD
role: PRINCIPAL_INVESTIGATOR
References: