Clinical trial NCT04538313: A Clinical Study in Patients With High-risk Recurrent Primary Hepatocellular Carcinoma Using Autologous TILs
Official title: Early Clinical Trials on Evaluating the Tolerance, Safety and Efficacy of Autologous TILs in High-risk Recurrent Primary Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hepatic Carcinoma
Keywords: TIL; HCC; clinical research
Lead sponsor: CAR-T (Shanghai) Cell Biotechnology Co., Ltd.
Sponsor class: NETWORK
Collaborators: name: Eastern Hepatobiliary Surgery Hospital
First posted: 2020-09-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Early clinical trials on evaluating the tolerance, safety and efficacy of autologous TILs in high-risk recurrent primary hepatocellular carcinoma


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years, gender unlimited;
2. Patients diagnosis of primary hepatocellular carcinoma by histopathology and/or cytology;
3. At the initial enrollment evaluation, patients were expected to accept radical resection of liver cancer and meet at least one of the following high-risk recurrence factors after surgery: ①There are 3 or more tumor lesions in the liver; ②The diameter of a single tumor lesion is \>8cm; ③Existence macrovascular tumor thrombus; ④\>5 MVI or MVI occurred in the distant paracancer tissues;
4. Before enrollment (after radical resection of liver cancer), imaging evaluation was performed to ensure that the tumor was completely removed (clear margin);
5. Must have at least 1 resectable lesion (diameter ≥2 cm);
6. ECOG score \<2;
7. Child-Pugh score ≤7;
8. Hematology and organ function indicators should be met simultaneously: (1) White blood cell count ≥3.0E+9/ L, neutrophil count ≥1.5E+9/ L, platelet countPlatelet count ≥8.0E10/ L, hemoglobin ≥80g/L (2) Liver function: aspartate aminotransferase (AST)≤5 times normal value, alanine aminotransferase (ALT)≤5 times normal value, bilirubin ≤5 times normal value, serum albumin ≥28 g/L; (3) Renal function: creatinine (Cr)≤1.5 times normal limit, creatinine clearance ≥50 mL/min;
9. An estimated life expectancy of ≥3 months;
10. Participation in this clinical study voluntary, can cooperate with researchers to carry out research, and sign informed consent.

Exclusion Criteria:

1. Primary hepatocellular carcinoma (HCC) has recurred in the past, or has other types of liver cancer at the same time (such as intrahepatic cholangiocarcinoma, mixed type of liver cancer);
2. Have a history of high fever or severe infection within 2 weeks prior to pretreatment, or are expected to undergo systemic anti-infective therapy or systemic steroid therapy during this trial;
3. Hepatic encephalopathy occurred within 2 weeks before pretreatment;
4. Previous or screening with autoimmune liver disease;
5. Screening with moderate or higher peritoneal effusion;
6. Clear neurological/psychiatric symptoms are known to be associated with brain metastases and/or assessed by MMSE;
7. Anti-tumor therapy such as chemotherapeutic drugs, targeted drugs, radio frequency ablation or minimally invasive intervention was received within 4 weeks before pretreatment;
8. Have received or are expected to participate in this study within 4 weeks before pretreatment to receive TIL required focus radiotherapy, or tumor evaluation focus (target focus or non-target focus) radiotherapy, or radical radiotherapy;
9. Any toxic response resulting from previous anti-tumor treatment prior to pretreatment did not return to grade 1 or below (CTCAE5.0 version);
10. Previous history of organ / stem cell transplantation or expected to be involved in this trial for organ / stem cell transplantation;
11. Left ventricular ejection fraction (LVEF)\<45% or New York Heart Association (NYHA)≥ grade 2;
12. Known or private HIV infection or syphilis infection;
13. The previous 3 years other system primary malignant tumor history (except skin basal cell carcinoma or cervical carcinoma in situ);
14. A known allergy to two or more non-homogeneous foods/drugs, or a known history of allergies to pre-treated drugs, including cyclophosphamide, fludarbin, interleukin;
15. Pregnant, lactating women or within one year of having a family plan;
16. Participated in other clinical trials within 3 months prior to screening;
17. Other circumstances that the researchers considered inappropriate to participate in the experiment.

Primary outcomes:
measure: DLT
timeFrame: 24 months
measure: Progression-Free Survival
timeFrame: 24 months
Secondary outcomes:
measure: Overall Survival Overall Survival
timeFrame: 24 months
measure: EQ-5D score
timeFrame: 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Eastern Hepatobiliary Surgery Hospital
state: Shanghai
Study officials:
References: