Hepatectomy Combined With Camrelizumab and Apatinib in CNLC Stage IIIb HCC

January 21, 2024 updated by: Jian-Hong Zhong, Guangxi Medical University

Hepatectomy Combined With Camrelizumab and Apatinib in CNLC Stage IIIb Hepatocellular Carcinoma

This study intends to prospectively enroll CNLC stage IIIb HCC cases with extrahepatic metastasis and intrahepatic lesions that are expected to be radical resected in several domestic clinical centers, and observe the OS and ORR, DCR, DOR, TTP and PFS of patients receiving hepatectomy combined with apatinib + carrelli pearl treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Carrelizumab was approved by CFDA for second-line indication of hepatocellular carcinoma (HCC) in 2020. The AHELP study led to the CFDA approval of apatinib for second-line indication of HCC in 2021. RESCUE study (phase II) reported the efficacy and safety data of apatinib combined with carrelizumab in first-line (n= 70, 68.6% of CNLC stage IIIb) and second-line (n= 140, 75.8% of CNLC stage IIIb) in the treatment of advanced HCC. ORR was 46% and 25%, 2-year OS was 43% and 45%, median OS was 20.1 and 21.8 months, PFS was 6.4 and 5.5 months, and grade ≥3 adverse events were 78.6% and 76.7%, respectively.

Local progression of intrahepatic lesions of HCC is the most important and direct cause of death, while extrahepatic metastases such as lung and bone metastases progress slowly and pose a much lower threat to life than intrahepatic lesions. For CNLC stage IIIb HCC, although liver resection is not recommended by officical guidelines, for cases with resectable intrahepatic lesions, a number of retrospective studies suggest that patients in the hepatectomy (even palliative resection) group had significantly better OS than those in the nonsurgical group, with a median OS of up to 32 months in the hepatectomy group, significantly higher than 19.2 months in atzuzumab plus bevacizumab or 20.1 months in apatinib plus carrelizumab. Previous retrospective studies in our center also suggest that some HCC patients with extrahepatic metastasis can still benefit from hepatectomy for long-term survival. Other studies suggested that the larger the preoperative diameter of HCC tumor, the greater the probability of postoperative lung metastasis. The more advanced the intrahepatic tumor or the larger the tumor load, the more likely the extrahepatic metastasis. Therefore, hepatectomy combined with targeted drugs +ICI may be the best treatment for HCC with extrahepatic metastasis and radical resection of intrahepatic tumor.

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Phase 2
  • 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 Contact

Study Contact Backup

Study Locations

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

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age ≥18
  • CNLC stage IIIb HCC with extrahepatic metastasis (such as lymph node, lung, bone metastasis, but not brain metastasis) diagnosed by clinical imaging, and at least one measurable metastasis can be used as RECIST V1.1 to observe the objective efficacy of "targeted + immune" therapy on target lesions;
  • Local tumors of the liver are expected to be radically resected;
  • Liver function Child-Pugh grade A;
  • ICG R15 < 10%;
  • ECOG PS 0 or 1 score;
  • Estimated survival time ≥6 months;
  • Hematological indexes should meet the following conditions: hemoglobin ≥90 g/L; Neutrophil absolute count ≥1.5×109/L; Platelet ≥80×109/L; Total bilirubin ≤1.5×ULN; ALT 3 x ULN or less;AST 3 x ULN or less; Alkaline phosphatase (AKP) ≤2.5×ULN; Serum albumin ≥28 g/L; Serum creatinine ≤1.5×ULN;
  • The patient is unwilling to receive TACE or radiotherapy;
  • For women of childbearing age, contraceptive measures (such as intrauterine devices, contraceptive tablets or condoms) should be used during the clinical trial until 3 months after the clinical trial ends; Serum or urine HCG test was negative for women of childbearing age within 72 hours prior to study enrollment. Effective contraception should be used during the study period and for three months after the end of the study for male patients with fertile partners.

Exclusion Criteria:

  • Have a history or concurrence of other malignancies, except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
  • Have used or are currently using other immunosuppressive or chemotherapy drugs for HCC (including but not limited to atezolizumab, nivolumab, pembrolizumab, tislelizumab, toripalimab, sintilimab, camrelizumab, S-1, etc.);
  • Patients who have received TACE, radiotherapy or systemic therapy within the past 6 months;
  • The presence of congenital or acquired immune deficiency diseases (such as HIV positive);
  • Known severe allergic reactions to PD-1 mab;
  • Within 7 days of enrollment, body temperature of unknown etiology ≥ 38.5℃ or white blood cell count > 15 x 109/L;
  • Patients with hemorrhagic diseases (including but not limited to moderate/severe esophagogastric varices, gastrointestinal bleeding, hemorrhagic gastric ulcer, hemoptysis > 2.5 ml per day) within 3 months of enrollment;For cases with positive occult blood in stool, occult blood should be reexamined, and gastroenteroscopy should be performed if necessary);
  • Arterial or venous thrombosis, such as cerebrovascular accident (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc.), deep venous thrombosis and pulmonary infarction, etc., 6 months before enrollment;
  • Those who have a history of alcohol or psychotropic drug abuse and cannot get rid of it or have mental disorders;
  • Breast-feeding women;
  • Autoimmune diseases in active stage or previous autoimmune diseases (such as autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, etc.);
  • Were using immunosuppressant or hormone therapy 2 weeks before enrollment;
  • Grade 1 CTCAE was not recovered after less than 5 drug half-lives with the last use of molecular targeted therapy or due to adverse events caused by previous therapy;
  • Complicated with hepatic encephalopathy or brain metastasis;
  • Hypertension beyond drug control (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
  • Uncontrolled heart disease or symptoms (including but not limited to grade II or higher cardiac function, unstable angina, myocardial infarction in the past 1 year, supraventricular or ventricular arrhythmias requiring treatment or intervention);
  • Abnormal coagulation function (INR > 2.0, PT > 16 s), bleeding tendency or need thrombolytic therapy or anticoagulant therapy (but prophylactic use of low-dose aspirin or low-molecular weight heparin is permitted);
  • Hereditary or acquired blood diseases (such as hemophilia, thrombocytopenia, coagulation disorders, etc.);
  • Urine protein ≥ ++ and 24-hour urine protein ≥ 1.0g in routine urine tests.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hepatectomy Combined With Camrelizumab and Apatinib
Patients with CNLC IIIb hepatocellular carcinoma will receive hepatectomy. Two to four weeks later, they will receive camrelizumab and apatinib treatments.
Drug: Hepatectomy Combined With Camrelizumab and Apatinib
Patients with CNLC IIIb hepatocellular carcinoma will receive hepatectomy. Two to four weeks later, they will receive camrelizumab and apatinib treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 2 years
OS is defined as the time from the hepatectomy to death from any cause.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate of extrahepatic target lesions
Time Frame: 6 months
Objective response rate is defined as the proportion of patients with complete response or partial response.
6 months

Collaborators and Investigators

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

Sponsor

Guangxi Medical University

Collaborators

Jiangsu HengRui Medicine Co., Ltd.

Investigators

  • Principal Investigator: Bang-De Xiang, Ph.D, Guangxi Medical University Cancer Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

June 1, 2021

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

September 21, 2021

First Submitted That Met QC Criteria

September 21, 2021

First Posted (Actual)

September 30, 2021

Study Record Updates

Last Update Posted (Estimated)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 21, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCCA-HCC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The data underlying this article will be shared on reasonable request to the corresponding author.

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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