Trial Title:
The Synergistic Effect of Portal Venous Supply Control and Immunotherapy in Hepatocellular Carcinoma
NCT ID:
NCT05760430
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Bevacizumab
Apatinib
Conditions: Keywords:
Hepatocellular carcinoma
Portal Venous Supply Control
Immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Investigator)
Intervention:
Intervention type:
Combination Product
Intervention name:
PVE+cTACE+Camrelizumab+Apatinib
Description:
After cTACE, 3 mg/kg of Camrelizumab was injected intravenously once every three
weeks+250 mg of Apatinib mesylate tablets were taken orally once a day. PVE was performed
on the half liver with the largest tumor load 2 weeks after CTACE.
Arm group label:
Experimental Group
Intervention type:
Combination Product
Intervention name:
cTACE+Atirizumab+Bevacizumab
Description:
After cTACE, 1200 mg of Atirizumab+15 mg/kg of Bevacizumab was injected intravenously
every three weeks.
Arm group label:
Control group
Summary:
Hepatocellular carcinoma is one of the most common solid malignant tumors. The prognosis
of unresectable hepatocellular carcinoma is very poor. According to the current
literature and the clinical practice of our center, portal vein blood supply control may
have great potential in the synergistic treatment of unresectable hepatocellular
carcinoma. Thus, we hope to study the safety and efficacy of portal blood supply control
+TACE+ Camrelizumab + Apatinib combined therapy in initial unresectable hepatocellular
carcinoma through a single-center clinical trial, and explore the synergistic effect of
portal blood flow control in target immune therapy of hepatocellular carcinoma.
Detailed description:
Hepatocellular carcinoma (HCC) is one of the most common solid malignant tumors and the
main cause of cancer-related deaths worldwide. The main treatment method for patients
with unresectable or advanced HCC (such as patients with vascular invasion, distant
metastasis, or tumor-related symptoms) is systemic therapy such as immunotherapy combined
with targeted drugs. The median OS of patients treated with first-line bevacizumab
(T)+atilizumab (A) was 19.2 months, and the ORR was 30%; The median OS was 22 months and
the ORR was 36% when the Lenvatinib+Pembrolizumab (K-drug) regimen was used in the
second-line treatment of patients with unresectable HCC. At present, the combination of
domestic PD-L1 monoclonal antibody, Camrelizumab, and VEGFR-2 inhibitor, Apatinib, shows
great potential in the treatment of Chinese patients with unresectable HCC. Phase II data
shows that the ORR, DCR, mPFS, and mOS for first-line treatment are 34%, 77%, 5.7 months,
and 20.3 months respectively.
However, the benefits for patients are still very limited, and the clinical treatment of
non-resectable HCC is facing serious challenges. Therefore, it is necessary to take a
reasonable multidisciplinary comprehensive treatment strategy, to establish a new
effective treatment plan and further improve the prognosis and quality of life of
patients.
The anti-vascular treatment of HCC is the basis of immunotherapy and an important trigger
and intensifier. The reason and mechanism are that hepatocellular carcinoma can be
secondary to liver injury caused by various reasons, such as chronic alcohol consumption,
chronic hepatitis B and C infection, non-alcoholic fatty liver, etc., but all of them are
manifested by increased blood vessels and significant vascular abnormalities, which
suggests that blood supply plays an important role in the occurrence and development of
HCC. A large number of targeted anti-vascular drugs have been used in the treatment of
hepatocellular carcinoma. Angiogenesis inhibitors can specifically inhibit VEGF-mediated
dendritic cell maturation disorder, promote antigen presentation and T cell immune
response to tumor antigen; At the same time, it antagonizes angiogenesis, blocks tumor
blood supply, normalizes tumor blood vessels, and increases T cell infiltration in tumor
cells.
The hepatic artery is the main blood supply source of the tumor, so angiogenesis
inhibitors often combine with TACE to directly and effectively block the blood supply of
the tumor, which can not only effectively inhibit angiogenesis around the tumor, but also
delay the progress of tumor and thus improve the effect of tumor treatment. It is
noteworthy that portal vein blood flow also plays an important role in the occurrence and
development of HCC.
Angiogenesis inhibitors can directly or indirectly affect the portal vein blood flow and
improve the prognosis. It has been reported in the literature that angiogenic inhibitors
such as sorafenib and lenvatinib can significantly reduce portal vein pressure and
effectively prolong the survival period of advanced HCC.
Multiple blood supply blockages also show certain therapeutic significance. In post-line
treatment, dual/multiple anti-vascular therapies show therapeutic effects. For example,
the multi-target anti-vascular drug regorafenib can be used as the second-line drug after
the first-line treatment of sorafenib. The median survival period of
sorafenib+regorafenib second-line treatment is 24 months.
The response rate of targeted immunotherapy is higher in advanced patients with portal
vein tumor thrombus. Not only does the tumor focus shrink, but the tumor thrombus also
shrinks or even disappears. This may be because the lack of blood supply in the portal
vein further reduces the blood supply of the tumor and tumor thrombus, thus promoting the
response to systemic therapy.
In our previous clinical practice and research, we found that the control of portal vein
blood flow on the affected side may have synergistic anti-tumor effects. The advanced
patients treated with targeted immunotherapy combined with portal vein blood supply
control, such as portal vein embolization (PVE), showed a good treatment response. In the
future, while the volume of the residual liver increased, the tumor focus was
significantly reduced. The patients obtained the opportunity of surgical resection, and
some patients even achieved complete response (CR).
Embolization of the portal vein of the affected liver segment leads to an increase in the
blood supply of the residual liver in the future, and realizes a rapid increase in the
volume of the residual liver in the future, so as to ensure the quality and prognosis of
hepatectomy, which is a common method for patients with early liver cancer before
hepatectomy.
At present, there is no study on the use of a portal vein blood supply control combined
system for the treatment of unresectable HCC conversion. Based on the current research
and clinical practice, we propose a hypothesis that strengthening blood supply control is
conducive to the conversion treatment of HCC, and controlling the blood supply of the
portal vein has an important synergistic effect on the treatment of unresectable HCC.
Portal vein blood supply control combined with TACE and targeted immunotherapy can
further enhance the conversion rate of unresectable HCC, bring more opportunities for
patients' subsequent surgery or local treatment, and help to prolong the survival period
of patients.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Adult male or female aged ≥ 18;
2. Primary hepatocellular carcinoma confirmed by pathology;
3. There is no extrahepatic metastasis and portal vein tumor thrombus (Barcelona stage
b), which cannot be removed after the evaluation of the surgeon, but there is a
potential surgical opportunity after the tumor is significantly reduced;
4. Have not received treatment in the past;
5. At least 1 measurable lesion meeting the RECIST v1.1 or mRECIST standard;
6. Liver function is Child-Pugh A;
7. ECOG PS 0~1 before entering the group;
8. Organs and bone marrow are fully functional:
9 Expected survival period ≥ 3 months; 10. Women of childbearing age who have not
undergone surgical sterilization should take effective contraceptive measures within 3
months from enrollment to the end of the trial; 11. Sign a written informed consent and
be able to comply with the visit and relevant procedures specified in the plan.
Exclusion Criteria:
1. The patient has any history of active autoimmune disease or autoimmune disease;
2. The patient is using immunosuppressant or systemic hormone therapy to suppress
immune function;
3. Known central nervous system metastasis or hepatic encephalopathy;
4. Severe allergic reaction to other monoclonal antibodies;
5. Have a history of organ transplantation;
6. The patient has the serious basic disease and cannot tolerate treatment;
7. The patient has previously received other anti-PD-1 antibody treatment or other
anti-PD-1/PD-L1 immunotherapy, or has previously received apatinib treatment;
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Sheng Yan, Doctor
Phone:
13957161680
Email:
shengyan@zju.edu.cn
Contact backup:
Last name:
Xi Ma
Phone:
18768117002
Start date:
December 14, 2022
Completion date:
December 2024
Lead sponsor:
Agency:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Agency class:
Other
Source:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05760430
