SHRINK: 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

Sponsor

Celyad Oncology SA (Industry)

Overall Status

Unknown status

CT.gov ID

NCT03310008

Collaborator

(none)

Enrollment

Locations

Arms

44.8

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer Liver Metastasis	Biological: NKR-2 cells	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

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 cellsBiological: 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

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 7, 2017

Anticipated Primary Completion Date :

May 1, 2021

Anticipated Study Completion Date :

May 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose level 1 (escalation The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.	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 Names: NKG2D CAR-T cells
Experimental: Dose level 2 (escalation) The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.	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 Names: NKG2D CAR-T cells
Experimental: Dose level 3 (escalation) The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.	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 Names: NKG2D CAR-T cells
Experimental: Recommended dose level (expansion) The dose expansion arm will use the maximum tolerated dose.	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 Names: NKG2D CAR-T cells

Outcome Measures

Primary Outcome Measures

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 [up to resection (up to day 99 to day 126)]
DLT refers to any Grade 3 or higher toxicity or any Grade 2 or higher autoimmune toxicity that is experienced during treatment and within 14 days following the first NKR-2 dose, is new and at least possibly related to NKR-2 study treatment administered concurrently with chemotherapy
The objective response rate (ORR) before resection as measured by RECIST (version 1.1) [up to resection (up to day 99 to day 126)]
The objective response rate (ORR) is defined as the sum of the proportions of patients achieving CR or PR. The occurrence of ORR before resection will be reported.

Secondary Outcome Measures

The occurrence of AEs and SAEs and any toxicity corresponding to DLT definition during the study treatment until resection visit [up to resection (up to day 99 to day 126)]
The occurrence of AEs and SAEs and any toxicity corresponding to DLT definition during the study treatment until resection visit
The occurrence of surgery complications and the wound healing status until 60 days after resection visit [until 60 days after resection]
Surgery and wound healing complications experienced within the 60-day post-operative period in patients who underwent surgery will be reported as safety endpoints
The clinical benefit rate (CBR) before resection [up to resection (up to day 99 to day 126)]
The clinical benefit rate (CBR) is defined as the proportion of patients achieving CR, PR or SD. The occurrence of CBR before resection will be reported.
The occurrence of mixed response (MR) before resection [up to resection (up to day 99 to day 126)]
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)".
The resection rate [resection (day 99 to day 126)]
The presence of residual tumor following surgical resection will be assessed.
The occurrence of pathological response at surgery [resection (day 99 to day 126)]
Resected specimens. will be graded according to the two grading systems by Rubbia-Brandt et al. and Blazer et al.
The disease-free survival (DFS) or progression-free survival (PFS) [through study completion (up to month 28)]
The disease-free survival (DFS) is defined as the time from resection of liver metastases to recurrence of tumor or death from any cause. The progression-free survival (PFS) is defined as time from study registration in the study to the disease progression or death from any cause.
The event-free survival (EFS) [through study completion (up to month 28)]
The event-free survival (EFS) is defined as the time from registration in the study to any of the following events: progression, non-resectability, local or distant recurrence, or death from any cause.
The overall survival (OS) [through study completion (up to month 28)]
The overall survival (OS) is defined as the time from study 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women ≥ 18 years old at the time of signing the ICF
Patients with histologically proven colorectal adenocarcinoma with potentially resectable liver metastases,
No previous chemotherapy for metastatic CRC,
The patient is due to receive first-line metastatic chemotherapy regimen with FOLFOX as a neoadjuvant
The patient must have an ECOG performance status 0 or 1
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:

Patients who have received another cancer therapy within 2 weeks before the planned day for the apheresis
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
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
Patients who underwent major surgery within 4 weeks before the planned day for the first treatment
Patients with uncontrolled intercurrent illness or serious uncontrolled medical disorder
Patients who have received a live vaccine within 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

Locations

	Site	City	Country	Postal Code
1	Institut Jules Bordet	Brussels	Belgium	1000
2	Cliniques universitaires Saint-Luc	Brussels	Belgium	1200
3	Grand Hôpital de Charleroi	Charleroi	Belgium	6000
4	UZ Leuven	Leuven	Belgium	3000

Sponsors and Collaborators

Celyad Oncology SA

Investigators

Principal Investigator: Frédéric Lehmann, MD, Celyad Oncology SA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Celyad Oncology SA

ClinicalTrials.gov Identifier:

NCT03310008

Other Study ID Numbers:

CYAD-N2T-003

First Posted:

Oct 16, 2017

Last Update Posted:

Jun 16, 2020

Last Verified:

Jun 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neoplasm Metastasis

Liver Neoplasms

Study Results

No Results Posted as of Jun 16, 2020