The purpose of this study is to assess the efficacy and safety of combining autologous Tcm immunotherapy and TACE in HCC patients with MVI after radical resection. Patients will be assigned either to the experimental arm to receive autologous Tcm immunotherapy and TACE or to the active comparator (TACE alone).
Completed
Phase 2
Hepatocellular carcinoma (HCC) is one of the common cancer worldwide, which is the third
cause of cancer related deaths. Radical hepatic resection remains the main treatment for
hepatocellular carcinoma, the 5-year survival rate of HCC after surgery was 60-70%.
Unfortunately, HCC is prone to postoperative recurrence that more than 50% of patients
relapse within 2 years, which has become the key to restrict the therapeutic effect of
hepatocellular carcinoma. Microvascular invasion (MVI) is one of the main risk factors for
poor prognosis in HCC.
Autologous cell immunotherapy is to collect patient's own immune cells and then given back to
the patient after amplified in vitro that can improve the anti-tumor immune response. Tcm
(central memory T cells) are effective anti-tumor immune cells that exhibit the long-term
survival and self-renewal capacity in vivo. Autologous Tcm immunotherapy combining
chemotherapy, surgery or radiotherapy would effectively prolong survival period, prevent
tumor recurrence and metastasis, then improve quality of life in patients.
| Name | Type | Description | Interventions |
|---|---|---|---|
| TACE+Tcm group | Experimental | Experimental arm: TACE plus autologous Tcm immunotherapy to treat HCC. | |
| TACE group | Active Comparator | Active comparator: TACE to treat HCC. |
Inclusion Criteria:
1. Be willing and able to provide written informed consent for the study.
2. Subject has accepted radical hepatic resection, and preoperative imaging is no
vascular invasion.
3. Postoperative pathology confirmed Hepatocellular carcinoma with negative margin and
microvascular invasion (MVI).
4. Age between 18-75 years old.
5. Radiology confirmed complete response (CR) after radical surgery.
6. Child-Pugh A.
7. Eastern Cooperative Oncology Group(ECOG) body condition score 0.
8. Adequate hepatic and renal function:
Hemoglobin ≥ 9.0g/dl. Absolute neutrophil count (ANC) > 1,500/mm3. Platelets ≥
50,000/ul. Total bilirubin (TBIL) ≤ 2mg/dl. Alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) ≤ 5 the upper limit of normal (ULN) for the
institution.
Alkaline phosphatase (ALP) ≤ 4 the upper limit of ULN. Prothrombin time (PT) > 50% or
prothrombin time-international normalized ratio (PT-INR) < 2.3.
Serum creatinine (CREA) ≤ 1.5 the upper limit of ULN.
9. Female subjects have had a negative blood pregnancy test within 2 week,
10. Subjects be willing to use appropriate contraception during the trial and 2 weeks
after the last administration of immunotherapy.
11. Radiology such as CT and MRI were performed in 4 weeks before the study.
Exclusion Criteria:
1. Recurrent HCC.
2. Portal vein embolus.
3. Cardiovascular disease:
Evidence of NYHA functional class III or IV heart disease. Unstable coronary artery
disease (CAD) is not allowed, while Myocardial Infarction (MI) 6 months of starting
study is allowed.
Cardiac arrhythmias requiring antiarrhythmic drugs except β-blockers or digoxin are
not allowed.
Uncontrolled hypertension.
4. History of Human Immunodeficiency Virus (HIV) or syphilis infection.
5. Severe inflammation, NCI CTCAE Version 3.0 grade > 2.
6. Epilepsy requiring steroid or antiepileptic drugs.
7. History of allotransplantation.
8. History or any evidence of hemorrhage.
9. Subjects undergoing renal dialysis.
10. Pregnancy or breast-feeding.
11. Prior or undergoing cancers that primary sites are different from the carcinoma of
this study. Exceptions to this are:
Cervical carcinoma in situ (CIS) Cured basal cell carcinoma Superficial bladder tumor
Cured cancers over 3 years before the study
12. Uncontrolled Ascites by diuretic treatment.
13. History of encephalopathy.
14. Gastrointestinal hemorrhage in 30 days before the study.
15. History of esophageal variceal hemorrhage and it is no effective treatment to prevent
the recurrence of hemorrhage.
16. Major surgery except radical hepatic resection was performed in 4 weeks before the
study.
17. Autologous bone marrow transplantation (ABMT) in 4 weeks before the study.
18. Concurrent treatment on another clinical trial or treatment on another clinical trial
in 4 weeks before the study.
19. Drug abuse, medical treatment, mental illness or social disorders that would interfere
with subjects' participation, or confound the results of the trial.
20. Any condition that would interfere with or endanger the safety and compliance of
subjects.
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Recurrence-free Survival (RFS) Time |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Recurrence-free survival was defined as the interval (in months) between hepatectomy and diagnosis of recurrence using either intrahepatic recurrence or extrahepatic metastasis. |
| Measure: | Overall Survival (OS) Rate at 24 Months |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | Overall survival rate = the number of patients in TACE/TACE+Tcm group survived at 24 months/the number of total patients assigned into TACE/TACE+Tcm group. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Cancer Institute and Hospital, Chinese Academy of Medical Sciences |
June 11, 2020
