Back to resultsDose 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 (SHRINK)
Primary Purpose
Colon Cancer Liver Metastasis
Status
Unknown status
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
NKR-2 cells
Sponsored by
About this trial
This is an interventional treatment trial for Colon Cancer Liver Metastasis
Eligibility Criteria
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
Sites / Locations
- Institut Jules Bordet
- Cliniques universitaires Saint-Luc
- Grand Hôpital de Charleroi
- UZ Leuven
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Dose level 1 (escalation
Dose level 2 (escalation)
Dose level 3 (escalation)
Recommended dose level (expansion)
Arm Description
The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.
The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.
The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.
The dose expansion arm will use the maximum tolerated dose.
Outcomes
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
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)
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
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
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
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
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
The presence of residual tumor following surgical resection will be assessed.
The occurrence of pathological response at surgery
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)
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)
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03310008
Brief Title
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
Acronym
SHRINK
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
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Unknown status
Study Start Date
August 7, 2017 (Actual)
Primary Completion Date
May 2021 (Anticipated)
Study Completion Date
May 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celyad Oncology SA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Cancer Liver Metastasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose level 1 (escalation
Arm Type
Experimental
Arm Description
The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.
Arm Title
Dose level 2 (escalation)
Arm Type
Experimental
Arm Description
The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.
Arm Title
Dose level 3 (escalation)
Arm Type
Experimental
Arm Description
The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.
Arm Title
Recommended dose level (expansion)
Arm Type
Experimental
Arm Description
The dose expansion arm will use the maximum tolerated dose.
Intervention Type
Biological
Intervention Name(s)
NKR-2 cells
Other Intervention Name(s)
NKG2D CAR-T cells
Intervention Description
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).
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
up to resection (up to day 99 to day 126)
Title
The objective response rate (ORR) before resection as measured by RECIST (version 1.1)
Description
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.
Time Frame
up to resection (up to day 99 to day 126)
Secondary Outcome Measure Information:
Title
The occurrence of AEs and SAEs and any toxicity corresponding to DLT definition during the study treatment until resection visit
Description
The occurrence of AEs and SAEs and any toxicity corresponding to DLT definition during the study treatment until resection visit
Time Frame
up to resection (up to day 99 to day 126)
Title
The occurrence of surgery complications and the wound healing status until 60 days after resection visit
Description
Surgery and wound healing complications experienced within the 60-day post-operative period in patients who underwent surgery will be reported as safety endpoints
Time Frame
until 60 days after resection
Title
The clinical benefit rate (CBR) before resection
Description
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.
Time Frame
up to resection (up to day 99 to day 126)
Title
The occurrence of mixed response (MR) before resection
Description
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)".
Time Frame
up to resection (up to day 99 to day 126)
Title
The resection rate
Description
The presence of residual tumor following surgical resection will be assessed.
Time Frame
resection (day 99 to day 126)
Title
The occurrence of pathological response at surgery
Description
Resected specimens. will be graded according to the two grading systems by Rubbia-Brandt et al. and Blazer et al.
Time Frame
resection (day 99 to day 126)
Title
The disease-free survival (DFS) or progression-free survival (PFS)
Description
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.
Time Frame
through study completion (up to month 28)
Title
The event-free survival (EFS)
Description
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.
Time Frame
through study completion (up to month 28)
Title
The overall survival (OS)
Description
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.
Time Frame
through study completion (up to month 28)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frédéric Lehmann, MD
Organizational Affiliation
Celyad Oncology SA
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Cliniques universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Grand Hôpital de Charleroi
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
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