Clinical trial NCT04011033: Study of Adoptive Transfer of iNKT Cells Combined With TAE/TACE to Treat Unresectable HCC
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Lead sponsor: Beijing YouAn Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Shijitan Hospital, Capital Medical University
name: Beijing Ditan Hospital
First posted: 2019-07-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival(PFS)
timeFrame: From date of enrollment to disease progression according to mRECIST, or death from any cause, whichever occurred first，approximately 2 years.
Secondary outcomes:
measure: Overall Survival(OS)
timeFrame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months.
measure: Objective Response Rate(ORR)
timeFrame: Evaluation was performed at the 12th week after the start of the treatment.
measure: Disease Control Rate (DCR)
timeFrame: Evaluation was performed at the 12th week after the start of the treatment.
measure: Adverse Events(AEs)
timeFrame: 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.
measure: Time to Quality of Life (QoL) Deterioration
timeFrame: Data will be collected at baseline and every 4 weeks until disease progression, then every 8 weeks for up to 60 weeks.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Youan Hospital,Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing YouAn Hospital
name: Jun Lu, Director
role: STUDY_CHAIR
References: