Palliative Hepatectomy Combined With Targeted Therapy and Immunotherapy for Advanced Hepatocellular Carcinoma
Palliative Hepatectomy Combined With Targeted Therapy and Immunotherapy for Advanced Hepatocellular Carcinoma
Sponsors
Source
Tongji Hospital
Oversight Info
Has Dmc
No
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
Brief Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the leading
cause of cancer-related death worldwide. Surgical resection has always been the best hope
for long-term survival of patients with HCC. However, due to the fact that most patients
are already in the middle and late stages of treatment, only about 20% of patients have
the opportunity to undergo surgical resection. Palliative cytoreductive surgery has been
used in the treatment of a variety of malignant tumors, but it is not recommended for the
treatment of HCC. Under the premise of targeted therapy and immunotherapy, palliative
hepatectomy can reduce tumor burden and may further improve the therapeutic effect of
HCC. The aim of this study is to explore whether palliative hepatectomy combined with
targeted therapy and immunotherapy can improve the therapeutic effect of advanced HCC,
ultimately prolong the survival time of patients, and provide a new treatment direction
for patients with advanced HCC.
Detailed Description
This study is a prospective, multicenter, single-arm clinical study aimed at evaluating
targeted therapy and immunotherapy combined with palliative hepatectomy for the treatment
of advanced hepatocellular carcinoma. Patients who have been assessed as stage B or C of
Barcelona Clinic Liver Cancer (BCLC) will receive local treatment (transcatheter arterial
chemoembolization (TACE) or transcatheter arterial chemoembolization (HAIC)) or 90Y-SIRT
(yttrium-90 selective internal radiation therapy) combined with Lenvatinib and
Durvalumab. After receiving three months of combined treatment, patients in the stable
disease (SD) or progressive disease (PD) stage who have poor efficacy evaluated by
imaging will undergo palliative hepatectomy; patients in the complete response (CR) or
partial response (PR) stage after imaging evaluation will be excluded and continue to
receive systematic treatment. Patients need to discontinue targeted therapy and
immunotherapy one week before surgery.
Overall Status
Recruiting
Start Date
2024-06-01
Completion Date
2028-06-01
Primary Completion Date
2027-06-01
Phase
Phase 1
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Objective Response Rate (ORR) |
6 weeks after first dose of Durvalumab |
Secondary Outcome
Measure |
Time Frame |
|
Overall Survival (OS) |
through study completion, an average of 2 year |
|
Progression Free Survival (PFS) |
18 months |
Enrollment
50
Condition
Intervention
Intervention Type
Procedure
Intervention Name
Description
Patients will receive TACE, HAIC, or 90Y-SIRT combined with Lenvatinib and Durvalumab.
After receiving three months of combined treatment, patients in the SD or PD stage who
have poor efficacy evaluated by imaging will undergo palliative hepatectomy.
Palliative Hepatectomy:① Intrahepatic metastasis: complete lesion resection of the main
tumor on one side of the liver; ② Extrahepatic metastasis: complete lesion resection of
intrahepatic lesions; ③ Merge portal vein tumor thrombus or hepatic vein tumor thrombus:
remove the tumor thrombus and completely remove the intrahepatic lesions. And reduce the
tumor burden by more than 90% through surgical resection.
Arm Group Label
Palliative Hepatectomy Combined With Targeted Therapy and Immunotherapy
Intervention Type
Drug
Intervention Name
Description
Starting two weeks post-surgery, patients began intravenous infusions of the PD-L1
monoclonal antibody, Durvalumab.
Arm Group Label
Palliative Hepatectomy Combined With Targeted Therapy and Immunotherapy
Other Name
IMFINZ
Intervention Type
Drug
Intervention Name
Description
Three weeks post-surgery, patients commenced oral administration of Lenvatinib.
Arm Group Label
Palliative Hepatectomy Combined With Targeted Therapy and Immunotherapy
Other Name
LENVIMA
Eligibility
Criteria
Inclusion Criteria:
1. Patients aged 18 to 75 years (inclusive).
2. No prior systemic antitumor treatment or surgical treatment.
3. Clinical or pathological diagnosis of hepatocellular carcinoma (HCC).
4. The primary liver lesion is mainly isolated liver tumors, with a tumor burden
exceeding 90% of the total tumor burden, and technically capable of complete
resection. Simultaneously merging ① intrahepatic metastasis: the number of
metastatic tumors is ≥ 3 and the sum of tumor diameters is ≤ 3cm; Or ② Extrahepatic
metastasis: Extrahepatic metastasis does not exceed one organ, metastatic tumors do
not exceed three, and the total diameter does not exceed 3cm. Or ③ if combined with
portal vein tumor thrombus or hepatic vein tumor thrombus, it can be removed or
completely removed together with the main tumor, and the tumor thrombus does not
enter the superior mesenteric vein or inferior vena cava.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, without
significant organ dysfunction.
6. Child-Pugh class A.
7. HBV-DNA less than 1*10^5 copies/ml and undergoing antiviral therapy.
8. Important organ functions meeting the following criteria: White Blood Cell (WBC)
≥2.5 × 10^9/L ;Platelet (PLT) ≥75 × 10^9/L;Hemoglobin (HB) ≥ 9g/dL;Alanine
aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3*ULN, Total Bilirubin
≤ 3*ULN; International Normalized Ratio (INR) ≤ 1.5*ULN; Prothrombin Time ≤ 1.5*ULN;
Creatinine ≤ 1.5*ULN.
9. Expected survival time of more than 3 months.
10. According to the RECIST v1.1 standard, postoperative patients with at least one
longest diameter of 1 cm or more measurable tumors.
11. Willing to provide informed consent.
Exclusion Criteria:
1. History of or concurrent active malignancy (excluding malignancies that have been
cured for over 5 years or in situ cancers that can be completely cured with adequate
treatment).
2. Presence of central nervous system metastasis or a history of brain metastasis.
3. History of organ transplantation.
4. History of surgery in the head, chest, or abdomen within the past six months.
5. Child-Pugh class C liver function or massive ascites.
6. Ongoing active infection within 7 days after completion of systemic antibiotic
therapy.
7. Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or
myocardial infarction within the past 12 months before enrollment.
8. Thrombotic or embolic events within the past 12 months, such as cerebrovascular
accidents (including transient ischemic attacks), pulmonary embolism, or deep vein
thrombosis.
9. New York Heart Association (NYHA) class II or above congestive heart failure.
10. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency
syndrome (AIDS), positive syphilis serology, untreated active hepatitis (defined as
HBV-DNA ≥ 10^5 copies/ml; HCV-RNA higher than the lower limit of detection for the
assay).
11. Any active, known, or suspected autoimmune disease. Stable subjects not requiring
systemic immunosuppressive therapy may be included, such as those with type 1
diabetes, hypothyroidism requiring only hormone replacement therapy, and skin
diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, and alopecia).
12. Interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic
diseases (e.g., diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
13. Pregnant or lactating women or females with a positive pregnancy test prior to the
first dose who have the potential for pregnancy.
14. The investigator deems the subject inappropriate for participation in this clinical
study due to any clinical or laboratory abnormalities or compliance issues.
15. Severe psychological or mental abnormalities.
16. Participation in another drug clinical trial within the past 4 weeks.
17. Other reasons that the investigator considers unsuitable for enrollment.
Gender
All
Minimum Age
18 Years
Maximum Age
75 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Zhiyong Huang |
Principal Investigator |
Tongji Hospital |
Overall Contact
Last Name
Zhiyong Huang
Phone
86-13995507729
Zyhuang126@126.com
Location
Facility |
Status |
Contact |
|
Tongji Hospital Wuhan Hubei China |
Recruiting |
Last Name: Zhiyong Huang Phone: 86-13995507729 Email: Zyhuang126@126.com |
Location Countries
Country
China
Verification Date
2024-06-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor-Investigator
Investigator Affiliation
Tongji Hospital
Investigator Full Name
Zhiyong Huang
Investigator Title
Professor
Keywords
Has Expanded Access
No
Number Of Arms
1
Intervention Browse
Mesh Term
durvalumab
lenvatinib
Arm Group
Arm Group Label
Palliative Hepatectomy Combined With Targeted Therapy and Immunotherapy
Arm Group Type
Experimental
Description
Reduce tumor burden by over 90% through palliative hepatectomy . Starting two weeks
post-surgery, patients began intravenous infusions of the PD-L1 monoclonal antibody,
Durvalumab, at a dosage of 1500 mg every three weeks. Three weeks post-surgery, patients
commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on
body weight: 8 mg (≤60 kg) or 12 mg (>60 kg), once daily. The use of Durvalumab and
Lenvatinib continued until the primary endpoint or other criteria specified in the
protocol for terminating the study treatment.
Firstreceived Results Date
N/A
Overall Contact Backup
Last Name
Erlei Zhang
baiyu19861104@163.com
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
June 17, 2024
Study First Submitted Qc
June 17, 2024
Study First Posted
June 24, 2024
Last Update Submitted
June 17, 2024
Last Update Submitted Qc
June 17, 2024
Last Update Posted
June 24, 2024
ClinicalTrials.gov processed this data on October 02, 2026
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.