A Study of MG4101 (Allogeneic Natural Killer Cell) for Intermediate-stage of Hepatocellular Carcinoma

Multi-center, Open, Phase 2a Clinical Trial to Evaluate the Efficacy and Safety of MG4101 in Hepatocellular Carcinoma After TACE

The propose of this study is evaluate the safety and efficacy of MG4101 (allogeneic Natural killer cells) in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE).

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: MG4101

Detailed Description

This is randomized, multi-center, open-labeled, Phase 2a study in patients with HCC after transarterial chemoembolization (TACE). A total of 78 patients will be randomized(1:1) into one of the two group, to receive adjuvant therapy using MG4101 (allogeneic Natural killer cells, Treatment group) or no adjuvant therapy (Control group).

Patients who were assigned Treatment group will receive 2 cycles of MG4101 (each cycle is 3 treatments at a frequency of once per week, between each cycle has 3 weeks of withdrawal period). After treatment period, patients will undergo follow up for progression and survival every 12 weeks (± 7 days) and follow up 1 year after the last patient's enrollment date.

The Control group's patients will will undergo follow up for progression and survival every 12 weeks (± 7 days) and follow up 1 year after the last patient's enrollment date.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Seoul Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Korea Univ. Guro hospital
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Suwon, Korea, Republic of
    • Ajou Univ. Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Patients who are between 20 to 80 years of age
2. Life expectancy > 12 weeks

3. Patients have complete remission according to the mRECIST by Dynamic contrast-enhanced 3- or 4-phase CT or tissue biopsy

   • Patients were diagnosed Hepatocellular Carcinoma BCLC stage B be-fore TACE.
   • Dynamic contrast-enhanced CT must be within 4 weeks after the TACE.

4. Previous TACE with the following:

   • Lipiodol mixed with chemotherapy (such as adriamycin etc.)
   • Used with Gelatin sponge or Polyvinyl alcohol or microsphere.
5. Patients who had local treatment such as Resection, Radiofrequency Ablation, Percutaneous ethanol injection and Transarterial chemoembolization can participates study.
6. Patients whose Child-Pugh score is less than B8.
7. Patients whose ECOG score is 0

8. Patients who satisfy the following conditions of the blood test, kidney function test, and liver function test.

   • Absolute neutrophil count ≥ 1,000 x 10^6 /L
   • hemoglobin level ≥ 8.5 g/㎗
   • platelet count ≥ 50,000 /㎣
   • Total bilirubin < 3.0 ㎎/㎗
   • Serum creatinine ≤ 1.5 x upper normal limit (UNL)
   • Total Albumin ≥ 2.8 ㎎/㎗
9. Able and willing to provide written informed consent and to comply with the study protocol.

Exclusion criteria

1. Patients who have metastasis.
2. Patients who have Portal vein or hepatic vein invasion.

3. Patient with medical history for the following:

   • Patients with Living donor Liver Transplantation or Orthotopic liver transplantation.
   • Patients who have received anti-cancer chemotherapy for 4 weeks prior to the study.
   • Patients who have not recovered adverse reaction prior to the study.
   • Patients who have received external beam radiation on liver, immunotherapy, cell therapy, and target therapy.
   • Prior use of systemic anticancer chemotherapy twice.
4. Patients who have a history of malignant tumors in 5 years prior to the study with the exception of Carcinoma in situ..
5. Patients who have a history of autoimmune disease such as Rheuma-toid arthritis, systemic Lupus Erythematosus, Vasculitis, Multiple sclerosis, Adolescent Insulin-dependent Diabetes Mellitus, etc.
6. Patients who have history of human immunodeficiency virus (HIV) infection.
7. Patients who have participated in other clinical trials within 4 weeks prior to this study.
8. Patients who treated with immunosuppressant for 3 months prior to this study.
9. Patients who have any condition that was uncontrolled or needed treatment.
10. Pregnant or breast-feeding subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: The Control Group; Patients will be randomized 1:1 to the control group and the treatment group. Patients who had allocated control group will not receive adjuvant treatment.
Experimental: The Treatment Group (MG4101); Patients will be randomized 1:1 to the control group and the treatment group. The treatment group will receive 6 times of MG4101(allogeneic natural killer cells) on week 0, 1, 2, 5, 6, 7.	Biological: MG4101; MG4101 is ex vivo-expanded, allogeneic natural killer cells. MG4101 were manufactured from normal healthy donor who underwent lymphopheresis under good manufacturing practice (GMP) conditions.; Other Names: allogeneic natural killer cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time To progression	every 12 weeks, up to the time of death or 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	every 12 weeks, up to the time of death or tumor progression, up to 18 months
Overall survival	every 12 weeks, up to the time of death, up to 18 months
change of Tumor Markers(AFP, Alpha-Fetoprotein)	every 12 weeks, up to the time of death or tumor progression, up to 18 months
Safety of MG4101 as evaluated by Incidence of adverse events (AEs), serious adverse events (SAEs)	up tp 9 weeks

Collaborators and Investigators

• Sponsor: GC Cell Corporation
• Investigators: Principal Investigator: Jung Hwan Yoon, M.D., Ph.D., Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2016
• Primary Completion (Actual): September 27, 2018
• Study Completion (Actual): September 17, 2019

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: July 31, 2016
• First Posted (Estimate): August 4, 2016

Study Record Updates

• Last Update Posted (Actual): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: MG4101-HCC-P2a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No