Immunotherapy using tumor-infiltrating lymphocytes for advanced liver cancer

Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Advanced Liver Cancer

This study is testing a new treatment using patients' own immune cells to see if it can help people with advanced liver cancer who haven't had success with other therapies.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Tongji Hospital (other)
• Drugs / interventions: cyclophosphamide, fludarabine
• Locations: 1 site (Wuhan)
• Trial ID: NCT06084299 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) for patients with advanced liver cancer. Participants will undergo a non-myeloablative lymphodepletion preparative regimen followed by intravenous infusion of their own TILs, along with interleukin-2 (IL-2) treatment. The goal is to assess the safety and efficacy of this innovative approach in patients who have not responded to standard treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with histologically confirmed advanced liver cancer who have experienced disease progression after at least two prior treatments.

Not a fit: Patients with early-stage liver cancer or those who have not undergone previous treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced liver cancer who have limited effective therapies available.

How similar studies have performed: Other studies using adoptive cell therapy for various cancers have shown promising results, suggesting potential success for this approach in liver cancer as well.

Eligibility criteria

Inclusion Criteria:

* The subjects must be informed of the study before the test and voluntarily sign a written informed consent.
* Age of the patients was between 18\~70 years
* Eligible patients have histologically proven advanced liver cancer
* Eastern Cooperative Oncology Group (ECOG) performance status was 0-1
* Metastatic lesions are confirmed by PET-CT, CT, MR and/or intraoperative exploration (more than 3, at least one accessible metastasis to procure for TILs)
* Patients have at least one separate additional measurable tumour lesion according to RECIST version 1.1 standard.
* The disease has progressed after at least two previous lines of standard treatment and there is no effective treatment option available
* Adequate normal organ and marrow function were present, including absolute neutrophil count ≥ 1×10\^9/L, leukocyte count ≥ 3×10\^9/L, platelet count ≥ 75×10\^9/L, hemoglobin ≥ 80 g/L, AST and ALT ≤ 2× of upper limit of normal, Serum creatinine ≤ 1.5× upper normal limits, Serum total bilirubin ≤ 1.5× upper normal limits
* Female subjects of childbearing age must have a negative urine or serum HCG test within 7 days before cell reinfusion
* Provide at least one gram of fresh tumor tissue and 10ml of peripheral blood for whole exome sequencing and TIL isolation and culture.
* Expected survival was at least 3 months
* Child-Push liver function score grade is A within seven days before the cell reinfusion.

Exclusion Criteria:

* With previous or concurrent other active cancer (except carcinoma in situ that has been cured without onset within 5 years, or those that can be cured by adequate treatment)
* Patients with metastasis to Central Nervous System or brain
* Have received organ transplantation in the past
* Received major liver surgery within 4 weeks before the first administration (except liver metastases biopsy).
* Received local treatment of the liver or other parts within 4 weeks before the first administration (transcatheter arterial chemoembolization \[TACE\], transcatheter arterial embolization \[TAE\], hepatic artery infusion \[HAI\], radiotherapy, radioembolization or ablation). Subjects are not eligible to participate in the study if the above-mentioned treatment is carried out between the last dose of sorafenib or oxaliplatin-containing regimen and the first study administration.
* After CT angiography examination, there is severe arterial embolism or hepatic artery vascular variation.
* APTT or PT \>= 5 UNL, or with bleeding evidence in two months or bleeding history in prior to the clinical study, no matter how serious it is
* Active inflammation within 7 days after systemic antibiotics treatment
* Subjects who have undergone major surgery or severe trauma such as laparotomy, thoracotomy, and laparoscopic organ removal within 4 weeks before enrollment.
* Active coronary artery disease, serious or unstable angina pectoris, or newly diagnosed angina pectoris or myocardial infarction within 12 months prior to the clinical study
* Thrombosis or embolism event within 12 months prior to the clinical study, such as cerebrovascular accident ( including TIA) or pulmonary embolism
* Congestive heart failure of NYHA \>= Class II
* Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml C Hepatitis, defined as HCV-RNA higher than the detection limit of the analytical method) or co-infection with hepatitis B and hepatitis C.
* Presence of any active, known or suspected autoimmune disease. Subjects in a stable state who do not require systemic immunosuppressive therapy are allowed, such as: type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin diseases that do not require systemic therapy (e.g., vitiligo, psoriasis disease and hair loss).
* Any interstitial lung disease, noninfectious causes of lung inflammation, or uncontrolled systemic disease (e.g. diabetes, pulmonary fibrosis, or acute pneumonia)
* Any adverse event of CTCAE (Ver 5.0) grade 2 or higher induced by previous treatment, except anemia, hair loss, and skin pigmentation
* Pregnant or lactating women or those who are positive in pregnancy test before 1st injection
* The investigator believes that the subject has any clinical or laboratory abnormalities or compliance problems and is not suitable for participating in this clinical study.
* With serious psychological or mental abnormalities
* Joined other clinical trials in four weeks prior to this study
* Patients who have a history of hypersensitivity to cyclophosphamide and fludarabine.
* Other researchers think that they are not suitable for enrollment.

Where this trial is running

Wuhan

• Tongji Hospital — Wuhan, China (RECRUITING)

Study contacts

• Principal investigator: Zhiyong Huang — Tongji Hospital
• Study coordinator: Tong Yuan

Conditions: Liver Cancer