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NCT Number: NCT04011033

Study of Adoptive Transfer of iNKT Cells Combined With TAE/TACE to Treat Unresectable HCC

Hepatocellular carcinoma (HCC) is a common disease with high mortality. More than 80% patients receive a diagnosis when their tumors are too advanced for curative approaches and have a dismal prognosis. invariant Natural Killer T (iNKT) cell exhibit antitumor activity against malignant tumors through producing high levels of cytokines. iNKT cells are abundant in the liver, but their function is defective in liver cancer. After expansion and restored function in vitro, iNKT cells can home to liver, then they play key antitumor function. We have finished a phase I study of adoptive transfer of autologous iNKT cells for treating patients with unresectable HCC. Safety and feasibility of iNKT infusion was proved. The purpose of this study was to verify the effectiveness of iNKT cell infusion in patients with unresectable HCC who had previously failed transcatheter arterial embolization (TAE) / transcatheter arterial chemoembolization (TACE).

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Key information

Conditions

Hepatocellular Carcinoma Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Beijing Youan Hospital,Capital Medical University

Beijing, Beijing Municipality, 100069, China

About this study

Patients with unresectable HCC will be enrolled and divided into two groups. Patients in trial group will be treated with combination of TAE/TACE and adoptive transfer of autologus iNKT cells. TAE/TACE will be performed at 0th and 4th week. iNKT cells will be infused at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy. Patients in control group will be treated with TAE/TACE at 0th and 4th week. Overall survival (OS) time, progression-free survival (PFS) time, objective response rate(ORR), disease control rate(DCR) will be monitored.

According to JSH guidelines, TAE/TACE failure is defined as an insufficient response after ≧2 consecutive TAE/TACE procedures that is evident on response evaluation computed tomography or magnetic resonance imaging after 1-3 months, these patients do not respond sufficiently to TAE/TACE.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-80 years.
  • Patients with hepatocellular carcinoma (BCLC, stageB/C) proved by histopathology or proved by CT or MRI imaging system, relapsed after previous therapy and no effective therapies known at this time.
  • Life expectancy of ≥ 12 weeks.
  • WBC>3.0×10^9/L, LYMPH> 0.8×10^9/L, Hb>85g/L, PLT>50×10^9/L, Cre<1.5×the upper limit of normal value.
  • iNKT>10 cell/mL in peripheral blood mononuclear cell (PBMC).
  • Able to understand and sign the informed consent.

Exclusion criteria

  • Any uncontrolled systematic disease: hypertension, heart disease, and et al.;
  • Portal vein tumor thrombus, central nervous system tumor metastasis, or combined with other tumors;
  • Receiving radiochemotherapy, local therapy, or targeting drugs within 4 weeks prior to this treatment;
  • Unstable immune systematic diseases or infectious diseases;
  • Combined with AIDS or syphilis;
  • Patients with history of stem cell or organ transplantation;
  • Patients with allergic history to related drugs and immunotherapy;
  • Patients with complications associated with liver diseases: moderate or severe pleural effusion, pericardial effusion, ascites, or gastrointestinal hemorrhage;
  • Pregnant or lactating subjects;
  • Unsuitable subjects considered by clinicians.

Treatment and study plan

iNKT cells

Biological

5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy.

Other names: invariant Natural Killer T cells

Human recombinated Interleukin-2

Drug

IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion.

Other names: IL-2

TAE/TACE

Procedure

TAE/TACE will be conducted to all patients at 0th week and 4th week.

Other names: Transcatheter Arterial embolization/Transcatheter Arterial chemoembolization

Primary outcomes

  1. Progression-Free Survival(PFS)

    Time frame: From date of enrollment to disease progression according to mRECIST, or death from any cause, whichever occurred first，approximately 2 years.

    PFS is the duration from the date of enrolled into clinical trial to the date of first documentation of tumor progression.

    Progression is defined using Modified RECIST (mRECIST),as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.

Secondary outcomes

  1. Overall Survival(OS)

    Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months.

    OS is the duration from the date of enrollment to the date of death due to any causes.

  2. Objective Response Rate(ORR)

    Time frame: Evaluation was performed at the 12th week after the start of the treatment.

    ORR is the proportion of patients who had a response rate including complete remission (CR) and partial remission (PR) evaluated by imaging according to mRECIST for target lesions and assessed by MRI/CT: Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions；Partial Response (PR), At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions; Overall Response (OR) = CR + PR.

  3. Disease Control Rate (DCR)

    Time frame: Evaluation was performed at the 12th week after the start of the treatment.

    DCR is the proportion of patients who had a response rate including complete remission (CR), partial remission (PR) and disease stabilization (SD) evaluated by imaging according to mRECIST for target lesions and assessed by MRI/CT: Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions；Partial Response (PR), At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions;Stable disease(SD), Any cases that do not qualify for either partial response or progressive disease. Disease Control Rate (DCR) = CR + PR + SD.

  4. Adverse Events(AEs)

    Time frame: The occurrence of AEs was observed for an average of 24 weeks after the completion of treatment (between 0-11 weeks of treatment) for up to a 60 week period in total.

    The severities of AEs will be divided into 5 levels according to the National Cancer Institute (NCI) Common Terminology Standard for Adverse Events (CTCAE) version 4.03.

  5. Time to Quality of Life (QoL) Deterioration

    Time frame: Data will be collected at baseline and every 4 weeks until disease progression, then every 8 weeks for up to 60 weeks.

    EORTC QLQ-C30: European Organization for Research on Treatment of Cancer Quality of Life Questionnare-Core 30.

    The totally 30 items spread out over five functional scales (15 items), three symptom scales (7 items), a global health status/QoL scale (2 items), and six single items. 1-28 item ranges 1: not at all, 2: a little, 3: quite a lit, 4: very much; 29-30 item ranges 1-7 from very poor to excellent. Raw score (RS) is an average of all items in each area. Standardized score is in the range of 0-100 by formula SS=[1-(RS-1)/n] x100 (function) or SS=[（RS-1）/n]x100 (symptom or overall health) respectively. A high scale score represents a higher/healthy response level.

    Time to deterioration was defined as a decrease from baseline of 10 points or more on the EORTC QLQ-C30 maintained for two consecutive assessments.

Sponsors and collaborators

Lead sponsor

Beijing YouAn Hospital

Other

Collaborators

  • Beijing Ditan Hospital
  • Beijing Shijitan Hospital, Capital Medical University

Registry information

Official study title

Study of Adoptive Transfer of Invariant Natural Killer T Cells Combined With TAE/TACE to Treat Unresectable Hepatocellular Carcinoma (HCC): Phase II Clinical Trial

Important dates

Study start
2018
Primary completion
2020
Study completion
2023
First posted
Jul 8, 2019
Registry last updated
Oct 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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