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

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

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

Study Overview

• Status: Unknown
• Conditions: Hepatic Carcinoma
• Intervention / Treatment: Drug: Tumor infiltrating lymphocyte

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200438
      • Eastern Hepatobiliary Surgery Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose group; 10^10 TIL	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.
Experimental: Low dose group; 10^9 TIL	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.
Experimental: Extension set; The number of TIL is decided by dose escalation experiment.	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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: CAR-T (Shanghai) Cell Biotechnology Co., Ltd.
• Collaborators: Eastern Hepatobiliary Surgery Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2020
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): October 31, 2022

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: August 28, 2020
• First Posted (Actual): September 4, 2020

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: TIL; HCC; clinical research
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: KT-2020-TIL001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No