Advanced Liver CancerPhase 3NCT04163237
Combined Immunotherapy and Targeted Therapy for Advanced Liver Cancer
A Phase 3 study testing PD-1 and Sorafenib in people with Advanced Liver Cancer, run by Guangxi Medical University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Advanced Liver Cancer
- What is being tested?
- PD-1 and Sorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2019to 30 Nov 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
TaoBai
Nanning, Guangxi, 530000
Tao Bai, MD, +86 13878862632, baitao@gxmu.edu.cn
About this study
Official title: 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.
- Conditions
- Advanced Liver Cancer
- Being tested
- PD-1, Sorafenib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1Drug
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.
SorafenibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| PD-1 & Sorafenib | Experimental | Not described Receives: Drug: PD-1; Drug: Sorafenib |
| Sorafenib | Other | Not described Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free Survival
Measured: 1 year
Secondary outcomes (1)
Overall Survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2019
- Study start1 Dec 2019 (estimated)
- Primary completion31 Oct 2020 (estimated)
- Study completion30 Nov 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Liver CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangxi Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, TaoBai, Guangxi Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04163237
- Sponsor's protocol ID
- GuangXiMU-HCC-PD1(2)
- Status last verified
- Nov 2019
- First submitted
- 6 Nov 2019
- Last updated
- 14 Nov 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on Combined Immunotherapy and Targeted Therapy for Advanced Liver Cancer
- ClinicalTrials.gov ID
- NCT04163237
- Acronym / sponsor ID
- GuangXiMU-HCC-PD1(2)
- Conditions
- Advanced Liver Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Guangxi Medical UniversityUniversity, hospital or other
- Study start
- 1 Dec 2019 (estimated)
- Primary completion
- 31 Oct 2020 (estimated)
- Study completion
- 30 Nov 2020 (estimated)
- First posted
- 14 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PD-1 & Sorafenib | Experimental | Drug: PD-1, Drug: Sorafenib |
| Sorafenib | Other | Drug: Sorafenib |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
- General inclusion criteria:
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-1PD-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 | PD-1 & Sorafenib |
| SorafenibSorafenib 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. | Drug | PD-1 & Sorafenib, Sorafenib |
Primary outcome
Disease-free Survival
Time frame: 1 year
1 secondary outcome
Overall Survival
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PD-1 and Sorafenib in people with Advanced Liver Cancer, run by Guangxi Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free Survival (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.