Resection+Highly Purified CTL Versus Resection Alone for HCC

Sun Yat-sen University

Status and phase: Unknown; Phase 3

Conditions: Hepatocellular Carcinoma

Treatments: Procedure: highly-purified CTL; Procedure: resection

Study type: Interventional

Funder types: Other

Identifiers

NCT02709070

HCC 005

Details and patient eligibility

About

There is little evidence showed that adjuvant therapy had been shown to extend the survival of patients with hepatocellular carcinoma (HCC) receiving surgical resection. We investigated whether injections of highly-purified Cytotoxic T lymphocytes prolongs recurrence-free survival of patients after resection for HCC.

Full description

Hepatocellular carcinoma (HCC) is the fifth most common and the third leading cause of cancer-related death worldwide. Resection is considered as the main curative treatment for HCC, but recurrence of tumor within the liver remnant is common, with a reported 5-year recurrence rate of 70%, which results in poor prognosis of HCC, and the high recurrence rate has led efforts to develop adjuvant therapies to reduce recurrence. However, the benefit of any form of adjuvant therapy remains unclear. Current guidelines didn't recommend any adjuvant therapy after resection. A previous clinical trial from Japan reported that cytokine-induced killer(CIK) cell immunotherapy increased recurrence-free survival (RFS) after surgical resection of HCC. Immunotherapy has become an optional treatment for HCC. Cytotoxic T lymphocytes(CTL), a kind of effective T cells that specific recognizing and killing antigen targeted cells through cloning amplification after receiving antigen information from antigen presented cell and playing key role to clear cancerous cells. There is little evidence for adjuvant CTL treatment for HCC receiving resection. So our hypothesis is that adjuvant highly-purified CTL is superior to resection alone for HCC. The aim of this prospective study is to compare the outcome of resection combined with highly-purified CTL with resection for HCC.

Enrollment: 210 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1. Age 18-75 years; 2. First diagnosed HCC, no other treatment received; 3.Child-pugh A-B 4. No severe coagulation disorders (prothrombin activity<40% or a platelet count<40,000/mm3); 5. Eastern Co-operative Oncology Group performance(ECOG) status 0-1.

Exclusion criteria

• 1. Pregnant women, breastfeeding women or plan pregnancy for the future 2 years; 2. The presence of vascular invasion or extrahepatic spread on imaging; 3. Usage of strong immunosuppressive agents such as corticosteroids, cyclosporine A within six months or longer; 4. HIV antibody or hepatitis C virus antibody positive; 5. Immunodeficiency diseases or autoimmune diseases (such as rheumatoid arthritis, Buerger's disease, multiple sclerosis and type 1 diabetes); 6. Suffering with cancers (except skin cancer, prostate cancer or cervical carcinoma in situ) at the enrolling time or 5 years before; 7. Suffering with other organ failure; 8. Suffering with severe mental illness; 9. Drug addiction (including alcohol) for 1 year before the enrolling time; 10. Participate in other Clinical trials within three months prior to 3 months before the enrolling time; 11. Other researchers believe that the patient is not fit for inclusion.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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210 participants in 2 patient groups

resection

Active Comparator group

Description:

Resection was carried out under general anesthesia using a right subcostal incision with a midline extension. Intra-operative ultrasonography was performed routinely to evaluate the tumor burden, liver remnant and the possibility of a negative resection margin. The investigators performed anatomical resection aiming at a resection margin of at least 1 cm. Pringle's maneuver was routinely used with a clamp and unclamp time of 10 minutes and 5 minutes, respectively. Hemostasis of the raw liver surface was done with suturing and application of fibrin glue.

Treatment:

Procedure: resection

highly-purified CTL

Experimental group

Description:

Peripheral blood (20-30mL) for manufacturing the individualized highly-purified CTL agent was collected from the respective participants who were randomized to the immunotherapy group before starting treatment. The highly-purified CTL agent was prepared at a central manufacturing facility. Participants in the immunotherapy group received a number up to 5×10E9 of the highly-purified CTL agent intravenously over 60 minutes without any premedication and then were observed for at least 30 minutes. Participants were scheduled to receive highly-purified CTL: 4-6 treatments at a frequency of once two-week during 6 months after receiving resection, followed by 6-9 treatments during 6 months to 2 years after receiving resection.

Treatment:

Procedure: highly-purified CTL

Procedure: resection