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

NCT04538313 | Unknown Phase 1

• 1 other identifier: KT-2020-TIL001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hepatic Carcinoma

Keywords

TIL; HCC; clinical research

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Overall Survival Overall Survival

  24 months

• EQ-5D score

  24 months

Study Arms (3)

High dose group

EXPERIMENTAL

10\^10 TIL

Drug: Tumor infiltrating lymphocyte

Low dose group

EXPERIMENTAL

10\^9 TIL

Drug: Tumor infiltrating lymphocyte

Extension set

EXPERIMENTAL

The number of TIL is decided by dose escalation experiment.

Drug: Tumor infiltrating lymphocyte

Interventions

Tumor infiltrating lymphocyte DRUG

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.

Extension set; High dose group; Low dose group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, gender unlimited;
• Patients diagnosis of primary hepatocellular carcinoma by histopathology and/or cytology;
• 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;
• Before enrollment (after radical resection of liver cancer), imaging evaluation was performed to ensure that the tumor was completely removed (clear margin);
• Must have at least 1 resectable lesion (diameter ≥2 cm);
• ECOG score \<2;
• Child-Pugh score ≤7;
• 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;
• An estimated life expectancy of ≥3 months;
• Participation in this clinical study voluntary, can cooperate with researchers to carry out research, and sign informed consent.

You may not qualify if:

• 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);
• 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;
• Hepatic encephalopathy occurred within 2 weeks before pretreatment;
• Previous or screening with autoimmune liver disease;
• Screening with moderate or higher peritoneal effusion;
• Clear neurological/psychiatric symptoms are known to be associated with brain metastases and/or assessed by MMSE;
• Anti-tumor therapy such as chemotherapeutic drugs, targeted drugs, radio frequency ablation or minimally invasive intervention was received within 4 weeks before pretreatment;
• 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;
• Any toxic response resulting from previous anti-tumor treatment prior to pretreatment did not return to grade 1 or below (CTCAE5.0 version);
• Previous history of organ / stem cell transplantation or expected to be involved in this trial for organ / stem cell transplantation;
• Left ventricular ejection fraction (LVEF)\<45% or New York Heart Association (NYHA)≥ grade 2;
• Known or private HIV infection or syphilis infection;
• The previous 3 years other system primary malignant tumor history (except skin basal cell carcinoma or cervical carcinoma in situ);
• 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;
• Pregnant, lactating women or within one year of having a family plan;

Sponsors & Collaborators

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

Study Sites (1)

Eastern Hepatobiliary Surgery Hospital

Shanghai, Shanghai Municipality, 200438, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: September 4, 2020
• Study Start: August 26, 2020
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: September 4, 2020

Record last verified: 2020-08

Locations

CN (1)