A Clinical Study in Patients With High-risk Recurrent Primary Hepatocellular Carcinoma Using Autologous TILs

Phase 1

• Conditions: Hepatic Carcinoma
• Interventions: Drug: Tumor infiltrating lymphocyte

• Registration Number: NCT04538313
• Lead Sponsor: CAR-T (Shanghai) Cell Biotechnology Co., Ltd.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-08
• Study Start: 2020-08-26
• Study First Submitted: 2020-08-26
• Study First Submitted QC: 2020-08-28
• Last Update Submitted: 2020-08-28
• Study First Posted: 2020-09-04
• Last Update Posted: 2020-09-04
• Primary Completion: 2022-10-31
• Study Completion: 2022-10-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
High dose group	Tumor infiltrating lymphocyte	10\^10 TIL
Low dose group	Tumor infiltrating lymphocyte	10\^9 TIL
Extension set	Tumor infiltrating lymphocyte	The number of TIL is decided by dose escalation experiment.

Primary Outcome Measures

Name	Time	Method
DLT	24 months	To evaluate the tolerability and safty of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.
Progression-Free Survival	24 months	To evaluate the tolerability and safty of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.

Secondary Outcome Measures

Name	Time	Method
Overall Survival Overall Survival	24 months	To evaluate the efficacy of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.
EQ-5D score	24 months	To evaluate the efficacy of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.

Trial Locations

Locations (1)

Eastern Hepatobiliary Surgery Hospital; 🇨🇳 Shanghai, Shanghai, China