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

Hepatic Carcinoma Clinical Trial

Official title:

Early Clinical Trials on Evaluating the Tolerance, Safety and Efficacy of Autologous TILs in High-risk Recurrent Primary Hepatocellular Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04538313
• Other study ID #: KT-2020-TIL001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 26, 2020
• Est. completion date: October 31, 2022

Study information

• Verified date: August 2020
• Source: CAR-T (Shanghai) Cell Biotechnology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: October 31, 2022
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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: ?There are 3 or more tumor lesions in the liver; ?The diameter of a single tumor lesion is >8cm; ?Existence macrovascular tumor thrombus; ?>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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatic Carcinoma

Intervention

Drug:
• Tumor infiltrating lymphocyte
Tumor infiltrating lymphocytes were isolated from tumor tissues from tumor biopsy or operation. These TILs were cultured in human IL-2 medium for 4 to 5 weeks. 10e9 to 10e10 TILs were yielded. The phenotype, function and sterile were detected before these TILs infused patients.

Locations

Country	Name	City	State
China	Eastern Hepatobiliary Surgery Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
CAR-T (Shanghai) Cell Biotechnology Co., Ltd.	Eastern Hepatobiliary Surgery Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DLT	To evaluate the tolerability and safty of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.	24 months
Primary	Progression-Free Survival	To evaluate the tolerability and safty of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.	24 months
Secondary	Overall Survival Overall Survival	To evaluate the efficacy of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.	24 months
Secondary	EQ-5D score	To evaluate the efficacy of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.	24 months