Combined Immunotherapy and Targeted Therapy for Advanced Liver Cancer

November 13, 2019 updated by: TaoBai, Guangxi Medical University

Study on Combined Immunotherapy and Targeted Therapy for Advanced Liver Cancer

Liver cancer is a common malignant tumor in China, and its incidence rate ranks third and remains high. The treatment of liver cancer has made some progress in recent years, mainly the progress of radical treatment such as surgery and ablation. For liver cancer, due to the emergence of molecularly targeted drugs such as sorafenib and immunological checkpoint inhibitors, the systemic therapeutic effect of advanced liver cancer is improved, and the curative effect is further improved. In recent years, immunotherapy has become one of the clinical treatment options for cancer. T lymphocytes are a cell with cell killing ability in the immune system, and programmed death factor 1 (PD-1) is an important inhibitory receptor on the surface of T lymphocytes. It is known that the ligands of PD-1 are PD-L1 and PD-L2, and studies have found that a variety of tumor cells have high expression of PD-L1 ligand on the surface. At present, clinical research on target drugs for PD-1 has included dozens of solid tumors or hematological tumors. The results of clinical studies that have been completed and the interim results of some studies indicate that anti- PD-1 antibody drugs are more effective and safer than previous treatments. Patients with hepatocellular carcinoma (HCC) often undergo liver cancer resection, but the recurrence rate can reach 70% to 100%, which seriously affects the treatment outcome and long-term survival rate. Early recurrence of liver cancer is mainly related to the invasiveness of the tumor. Microvascular invasion, non-anatomical hepatectomy, AFP greater than 32 ng/ml, tumor diameter greater than 5 cm, and incomplete tumor capsule are risk factors for recurrence within 2 years after surgery. Hence, it is necessary to determine the risk factors for HCC recurrence and the markers for continuous monitoring of anti-tumor response before and after surgery. Circulating tumor cells (CTCs) is an integral part of "liquid biopsy" and has great potential to change the current treatment modality in the cancer field. CTCs are derived from solid tumors and are associated with hematogenous metastasis. Therefore, analyzing the level of CTC has clinical guiding significance. For liver cancer patients, overall survival (OS) tended to be poorer in patients with CTCs. Although surgical treatment of liver cancer has benefited most patients with liver cancer, monitoring postoperative recurrence, further improving the long-term prognosis of liver cancer, postoperative detection of CTCs and other related indicators, combined with targeted, immune and other related treatments for further study. It is expected to receive 100 patients (50 treatment groups, 50 control groups). Patients who underwent immunotherapy after surgery were assigned to the immunotherapy group, and patients who were not treated with sorafenib after surgery were classified as the control group. All patients underwent 7 CTCs tests (immunomagnetic beads negative enrichment-targeted PCR) before, 7 days after surgery and 1st, 3rd, 6th, 9th, and 12th postoperatively. All patients were observed from the observation period. After the liver cancer resection, the patient was observed to have died, lost to follow-up or the end of the study.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangxi
      • Nanning, Guangxi, China, 530000
        • Recruiting
        • TaoBai
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Pathological diagnosis of primary hepatocellular carcinoma, BCLC stage A,B,C, liver function Chid-Pugh grade A, or liver function Child-Pugh classification changed from grade B to grade A after short-term liver treatment, PS score 0- 1 point. Received surgical treatment of primary hepatocellular carcinoma.

  • Laboratory inspection inclusion criteria:

    • Neutrophils ≥ 1.5 × 109 / L;
    • Platelets ≥ 50 × 109 / L;
    • Hemoglobin ≥ 90 g / L;
    • Serum creatinine ≤ 1.5 × upper limit of normal (ULN) and creatinine clearance ≥ 50 mL/min;
    • AST, ALT ≤ 2.5 × ULN;
    • Serum bilirubin ≤ 1.25 × ULN;
    • Patients who did not receive anticoagulant therapy: INR or aPTT ≤ 1.5 × ULN. If the patient received prophylactic anticoagulant therapy, the INR ≤ 2 × ULN within 14 days before the study treatment and the aPTT was within the normal range, the patients were acceptable for enrollment.
    • High risk factors for postoperative recurrence: Large blood vessels (2-pole branches) and bile duct invasion, or visible tumor thrombus;
    • Positive resection margin: Histopathological examination of the resected liver section indicatee residual tumor cells;
    • Two weeks after operation, AFP still ≥200 ug/L;
    • Preoperative lymph node involvement.

  • General inclusion criteria:

    • Age 18-75;
    • No anti-tumor treatment history before surgery;
    • Agree to provide tissue and pathological specimens;
    • ECOG 0 points;
    • For women of gestational age, no pregnancy plan and continued full contraception.

Exclusion criteria:

  • Pathological diagnosis of primary hepatocellular carcinoma, BCLC stage A, with radical resection, Child-Pugh grade C, PS score of 2 points and above. Biliary cells or mixed cell carcinoma confirmed by postoperative pathology. No surgery was performed.
  • Preoperative treatment of TACE or radiotherapy and chemotherapy, and targeted anti-tumor therapy.
  • One month after the operation, the rest of the anti-tumor treatment was performed, or combined with two or more anti-tumor pain treatment.
  • There were distant metastases before surgery.
  • Have a history of active autoimmune disease or autoimmune disease;
  • Inoculated with any anti-infective vaccine (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks before randomization;
  • Use immunosuppressive agents, or systemic, or absorbable local hormones to achieve immunosuppressive purposes (dose > 10 mg/day of prednisone or other equivalent hormones) and continue to be used within 2 weeks prior to randomization;
  • Any significant clinical and laboratory abnormalities;
  • Researchers believed that the patient effected safety evaluation, such as: uncontrollable active infections, uncontrolled diabetes, high blood pressure could not be reduced to the following range by monotherapy (systolic blood pressure < 140 mmHg, diastolic blood pressure < 90 mmHg), peripheral neuropathy grade II or above, congestive heart failure, myocardial infarction within 6 months, chronic kidney disease;
  • Main or main branch tumor thrombus (preoperative imaging or intraoperative findings) or extrahepatic disseminated or recurrent liver cancer.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PD-1 & Sorafenib
Drug: PD-1
PD-1 (programmed death receptor 1), an important immunosuppressive molecule, is an immunoglobulin superfamily and is a membrane protein of 268 amino acid residues. It was originally cloned from apoptotic mouse T cell hybridoma 2B4.11. Immunomodulation targeting PD-1 has important implications for anti-tumor, anti-infective, anti- autoimmune diseases and organ transplant survival. Its ligand PD-L1 can also be used as a target, and the corresponding antibodies can also play the same role. PD-1 and PD-L1 bind to initiate programmed cell death of T cells, allowing tumor cells to gain immune escape.
Drug: Sorafenib
Sorafenib tosylate is a novel multi- target anti-tumor drug developed by Bayer Pharmaceuticals, Germany, which acts on both tumor cells and tumor blood vessels. It has a dual anti-tumor effect: it directly inhibits tumor cell proliferation by blocking RAF/MEK/ERK-mediated cell signaling pathways, and also by inhibiting VEGFR and platelet- derived growth factor (PDGF) receptors. Blocking the formation of tumor neovascularization, indirectly inhibiting the growth of tumor cells.
Other: Sorafenib
Drug: Sorafenib
Sorafenib tosylate is a novel multi- target anti-tumor drug developed by Bayer Pharmaceuticals, Germany, which acts on both tumor cells and tumor blood vessels. It has a dual anti-tumor effect: it directly inhibits tumor cell proliferation by blocking RAF/MEK/ERK-mediated cell signaling pathways, and also by inhibiting VEGFR and platelet- derived growth factor (PDGF) receptors. Blocking the formation of tumor neovascularization, indirectly inhibiting the growth of tumor cells.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Disease-free Survival
Time Frame: 1 year
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Overall Survival
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guangxi Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 6, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 14, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 14, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GuangXiMU-HCC-PD1(2)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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