Back to resultsNatural Killer (NK) Cell Therapy in Locally Advanced HCC
Primary Purpose
Locally Advanced Hepatocellular Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Vax-NK/HCC
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Hepatocellular Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Subjects with intermediate and/or locally advanced HCC histologically confirmed by biopsy or by typical radiological findings.
- Subjects who were not suitable for or failed curative treatments such as surgical resection, local ablation therapy, transarterial chemoembolization (TACE), sorafenib, atezolizumab, bevacizumab, etc.
- Child-Pugh liver function class A or B.
- Subjects' ECOG performance status of 0 or 1.
- The presence of macrovascular invasion.
- Adequate liver, renal, and hematologic functions.
Exclusion Criteria:
- Subjects who received the immune cell-based therapy within 6 months before the screening visit.
- Subjects with a history of a malignancy other than HCC within the last 5 years, liver transplantation, and hypersensitivity to 5-FU or cisplatin.
- Subjects with extra-hepatic metastases.
- Subjects who have ongoing autoimmune disease.
- Female subjects who are pregnant or lactating or women of child-bearing potential but unable to take adequate contraception.
Sites / Locations
- Seon-Ah HaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Autologous NK cell infusion combined with HAIC
Arm Description
HAIC of 5-FU (500 mg/m2, Q4W) and cisplatin (15 mg/m2, Q4W) will be administered for up to 4 cycles to patients with locally advanced HCC. Subjects who achieved sustained SD or better based on the mRECIST criteria after 2nd cycle of HAIC will be enrolled to receive 1x10^9 cells VAX-NK/HCC infusion.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR) of administering VAX-NK/HCC combined with HAIC
ORR will be measured as the proportion of patients with a best overall response of complete response (CR) and partial response (PR) of administering VAX-NK/HCC combined with HAIC.
Secondary Outcome Measures
Disease control rate (DCR) of administering VAX-NK/HCC combined with HAIC
ORR will be measured as the proportion of patients with a best overall response of complete response (CR), partial response (PR), and stable disease (SD) of administering VAX-NK/HCC combined with HAIC.
Time to progression (TTP) of administering VAX-NK/HCC combined with HAIC
TTP will be measured by time to progression, defined as time from enrollment to disease progression.
Overall survival (OS) of administering VAX-NK/HCC combined with HAIC
OS will be measured as time from enrollment to death due to any cause.
Quality of Life of administering VAX-NK/HCC combined with HAIC
The assessment will be performed using the Korean versions of European Organization for Research and Treatment of Cancer (EORTC) Questionnaire 30 (QLQ-C30) consisting of 30 items. Total score: Range 0-100.
Adverse Events (AEs) and Serious Adverse Events (SAEs) of administering VAX-NK/HCC combined with HAIC
The assessment will be measured by determining the number of patients that experience AEs and SAEs graded according to the NCI-CTCAE (Version 4.0)
The proportions of T and NK cells
This will be measured by determining the relative percentages of CD4+CD8+ T cells and CD3- CD56+ NK cells in patients' peripheral blood.
The lymphocyte/monocyte ratio (LMR)
LMR will be calculated by dividing the absolute lymphocyte count by the absolute monocyte count in patients' peripheral blood.
The NK cell cytotoxicity
This will be measured by determining percent cell lysis of target cells (K562) in patients' peripheral blood.
The serum cytokine levels
The serum concentrations of IFN-γ, IL-10, and TGF-β will be measured in patients' serum using the Enzyme-Linked immunosorbent assays.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05040438
Brief Title
Natural Killer (NK) Cell Therapy in Locally Advanced HCC
Official Title
A Phase 2a Study Using Natural Killer (NK) Cell Therapy Combined With Hepatic Artery Infusion Chemotherapy (HAIC) in Patients With Locally Advanced Hepatocellular Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 15, 2019 (Actual)
Primary Completion Date
September 18, 2023 (Anticipated)
Study Completion Date
May 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vaxcell Bio, Co., Ltd.
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
This Phase 2a trial will evaluate the safety and efficacy of NK cell therapy combined with the hepatic artery infusion chemotherapy (HAIC) in patients with intermediate and/or locally advanced hepatocellular carcinoma (HCC). We hypothesized that 5-fluorouracil (FU) with immunomodulatory functions would relieve the immunosuppressive microenvironment from the myeloid-derived suppressor cells (MDSCs), thereby enhancing the anti-tumor activity of NK cells. Thus, the subsequent infusion of autologous NK cells (VAX-NK/HCC) following HAIC treatment may further improve the anti-tumor activity in patients with advanced HCC.
Detailed Description
Primary Objective I. To assess the objective response rate (ORR) of administering VAX-NK/HCC, autologous NK cells combined with HAIC in patients with locally advanced HCC.
Secondary Objectives I. To assess the efficacy of administering VAX-NK/HCC combined with HAIC. II. To assess the safety of administering VAX-NK/HCC combined with HAIC. III. To assess the immune responses of administering VAX-NK/HCC combined with HAIC.
OUTLINE: This is a Phase 2a study. Patients receive HAIC treatment every 4 week for up to 4 cycles followed by ex-vivo expanded autologous NK cell infusions. The NK cell treatment repeats every 4 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients will be followed until the disease progression.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Autologous NK cell infusion combined with HAIC
Arm Type
Experimental
Arm Description
HAIC of 5-FU (500 mg/m2, Q4W) and cisplatin (15 mg/m2, Q4W) will be administered for up to 4 cycles to patients with locally advanced HCC. Subjects who achieved sustained SD or better based on the mRECIST criteria after 2nd cycle of HAIC will be enrolled to receive 1x10^9 cells VAX-NK/HCC infusion.
Intervention Type
Biological
Intervention Name(s)
Vax-NK/HCC
Intervention Description
autologous NK cells expanded ex vivo.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) of administering VAX-NK/HCC combined with HAIC
Description
ORR will be measured as the proportion of patients with a best overall response of complete response (CR) and partial response (PR) of administering VAX-NK/HCC combined with HAIC.
Time Frame
average 6 months
Secondary Outcome Measure Information:
Title
Disease control rate (DCR) of administering VAX-NK/HCC combined with HAIC
Description
ORR will be measured as the proportion of patients with a best overall response of complete response (CR), partial response (PR), and stable disease (SD) of administering VAX-NK/HCC combined with HAIC.
Time Frame
average 6 months
Title
Time to progression (TTP) of administering VAX-NK/HCC combined with HAIC
Description
TTP will be measured by time to progression, defined as time from enrollment to disease progression.
Time Frame
average 6 months
Title
Overall survival (OS) of administering VAX-NK/HCC combined with HAIC
Description
OS will be measured as time from enrollment to death due to any cause.
Time Frame
average 12 months
Title
Quality of Life of administering VAX-NK/HCC combined with HAIC
Description
The assessment will be performed using the Korean versions of European Organization for Research and Treatment of Cancer (EORTC) Questionnaire 30 (QLQ-C30) consisting of 30 items. Total score: Range 0-100.
Time Frame
average 6 months
Title
Adverse Events (AEs) and Serious Adverse Events (SAEs) of administering VAX-NK/HCC combined with HAIC
Description
The assessment will be measured by determining the number of patients that experience AEs and SAEs graded according to the NCI-CTCAE (Version 4.0)
Time Frame
average 6 months
Title
The proportions of T and NK cells
Description
This will be measured by determining the relative percentages of CD4+CD8+ T cells and CD3- CD56+ NK cells in patients' peripheral blood.
Time Frame
average 6 months
Title
The lymphocyte/monocyte ratio (LMR)
Description
LMR will be calculated by dividing the absolute lymphocyte count by the absolute monocyte count in patients' peripheral blood.
Time Frame
average 6 months
Title
The NK cell cytotoxicity
Description
This will be measured by determining percent cell lysis of target cells (K562) in patients' peripheral blood.
Time Frame
average 6 months
Title
The serum cytokine levels
Description
The serum concentrations of IFN-γ, IL-10, and TGF-β will be measured in patients' serum using the Enzyme-Linked immunosorbent assays.
Time Frame
average 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects with intermediate and/or locally advanced HCC histologically confirmed by biopsy or by typical radiological findings.
Subjects who were not suitable for or failed curative treatments such as surgical resection, local ablation therapy, transarterial chemoembolization (TACE), sorafenib, atezolizumab, bevacizumab, etc.
Child-Pugh liver function class A or B.
Subjects' ECOG performance status of 0 or 1.
The presence of macrovascular invasion.
Adequate liver, renal, and hematologic functions.
Exclusion Criteria:
Subjects who received the immune cell-based therapy within 6 months before the screening visit.
Subjects with a history of a malignancy other than HCC within the last 5 years, liver transplantation, and hypersensitivity to 5-FU or cisplatin.
Subjects with extra-hepatic metastases.
Subjects who have ongoing autoimmune disease.
Female subjects who are pregnant or lactating or women of child-bearing potential but unable to take adequate contraception.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Seon-Ah Ha, Ph.D.
Phone
+82-61-375-8863
Email
seonah387@vaxcell-bio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seon-Ah Ha, Ph.D.
Organizational Affiliation
VaxCell Biotherapeutics Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Seon-Ah Ha
City
Hwasun
State/Province
Jeollanam-do
ZIP/Postal Code
58141
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seon-Ah Ha, Ph.D.
Phone
+82613758863
Email
seonah387@vaxcell-bio.com
First Name & Middle Initial & Last Name & Degree
Deok ha Kim, M.S.
Phone
+82613758863
Email
dh.kim@vaxcell-bio.com
12. IPD Sharing Statement
Learn more about this trial
Natural Killer (NK) Cell Therapy in Locally Advanced HCC
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