Individualized Comprehensive Treatment for Advanced Hepatocellular Carcinoma

NCT06893887 | Recruiting

• 1 other identifier: E2025-KT-005-01
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This project is a prospective, multi-center, multi-cohort exploratory clinical study. It focuses on patients with advanced hepatocellular carcinoma who experience disease progression after first-line standard therapy. Based on different patterns of disease progression, patients will receive relevant systemic treatments, either with or without local interventional therapy. The primary endpoint is progression-free survival (PFS), while secondary endpoints include overall survival (OS), 1-year OS rate, objective response rate (ORR), disease control rate (DCR), duration of remission (DOR), and safety. Additionally, the study will explore the correlation between patients' clinical pathological characteristics, serum biomarkers, and clinical efficacy.

Conditions

Hepatocellular Carcinoma(HCC)

Outcome Measures

Primary Outcomes (1)

• PFS（Progression-free Survival）

  Progression-free survival (PFS) was defined as the time from treatment initiation on Day 1 to the earliest occurrence of radiologically confirmed disease progression, as assessed by tumor imaging, or death from any cause, whichever came first. Evaluations were conducted by the investigator in accordance with RECIST v1.1.

  24 months

Secondary Outcomes (4)

• OS(Overall survival)

  48 months

• ORR(Objective response rate)

  24 months

• DCR(Disease control rate )

  24 months

• DOR(Duration of Response)

  24 months

Study Arms (10)

Arm 1

EXPERIMENTAL

XELOX/FOLFOX4+ Adebelizumab + Apatinib+Icaritin

Drug: FOLFOX4; Drug: Adebrelimab

Arm 2

EXPERIMENTAL

Adebelizumab + Apatinib+Icaritin

Drug: Adebrelimab; Drug: Apatinib; Drug: Icaritin

Arm 3

EXPERIMENTAL

SHR1701+ Apatinib+Icaritin

Drug: Apatinib; Drug: Icaritin; Drug: SHR-1701

Arm 4

EXPERIMENTAL

QL1706+ Apatinib+Icaritin

Drug: Apatinib; Drug: Icaritin; Drug: QL1706

Arm 5

EXPERIMENTAL

The original targeted combination immunotherapy+HAIC

Procedure: HAIC; Drug: The original treatment regimen

Arm 6

EXPERIMENTAL

SHR1701+ Apatinib+Icaritin，intrahepatic progression

Drug: Apatinib; Drug: Icaritin; Drug: SHR-1701

Arm 7

EXPERIMENTAL

QL1706+ Apatinib+Icaritin，extrahepatic progression

Drug: Apatinib; Drug: Icaritin; Drug: QL1706

Arm 8

EXPERIMENTAL

SHR1701+Bevacizumab+Icaritin

Drug: Icaritin; Drug: SHR-1701; Drug: Bevacizumab

Arm 9

EXPERIMENTAL

QL1706+Bevacizumab+Icaritin

Drug: Icaritin; Drug: QL1706; Drug: Bevacizumab

Arm 10

EXPERIMENTAL

Local treatment of oligometastases (such as radiotherapy, RFA, etc.) + the original targeted and immunotherapy.

Procedure: Local treatment; Drug: The original treatment regimen

Interventions

FOLFOX4 DRUG

FOLFOX4 was administered by oxaliplatin 85 mg/m² d1+ leucovorin 200 mg/m² d1-2+ fluorouracil 400 mg/m² 2 h→ 600 mg/m² 24 h d1-2 q2w, with a total of 4 cycles

Arm 1

Adebrelimab DRUG

Adebrelimab 1200mg, intravenous infusion, every 3 weeks

Arm 1; Arm 2

Apatinib DRUG

Apatinib 250mg, oral, once daily.

Arm 2; Arm 3; Arm 4; Arm 6; Arm 7

Icaritin DRUG

Epimedium extract soft capsules 2.4g, oral, 2 times daily.

Arm 2; Arm 3; Arm 4; Arm 6; Arm 7; Arm 8; Arm 9

SHR-1701 DRUG

SHR1701，30mg/kg, intravenous infusion, every 3 weeks, use for up to 2 years at most.

Arm 3; Arm 6; Arm 8

QL1706 DRUG

QL1706，5mg/kg, intravenous infusion, every 3 weeks, use for up to 2 years at most.

Arm 4; Arm 7; Arm 9

Bevacizumab DRUG

Bevacizumab 7.5mg, intravenous infusion, once every 3 weeks.

Arm 8; Arm 9

HAIC PROCEDURE

Hepatic Arterial Infusion Chemotherapy

Arm 5

Local treatment PROCEDURE

Local treatment of oligo-metastases.

Arm 10

The original treatment regimen DRUG

Continue the original targeted therapy combined with immunotherapy. dosage, dosage form,frequency of administration was the same as before.

Arm 10; Arm 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old, male or female
• Hepatocellular carcinoma patients diagnosed by cytology or tissue puncture, or who meet clinical diagnostic criteria and cannot be treated with radical treatment (radical surgery, ablation, radiotherapy, etc.)
• Disease progression after first-line targeted combined immune system therapy (as per RECIST1.1 criteria)
• Life expectancy exceeds 3 months
• ECOG physical condition score 0\~1
• Women of childbearing age must have a serum pregnancy study done within 7 days before the first medication, and the result is negative. Female subjects of reproductive age and male subjects whose partners are women of reproductive age must consent to contraception within 24 weeks from the date of signing the informed consent to the last administration of the study drug
• Before the first dose of the investigational drug, the laboratory test values met the following conditions: ①blood routine (no blood transfusion within 14 days before screening, no hematopoietic stimulating drug correction) : white blood cell count (WBC) ≥ 2.0 × 109/L; platelet (PLT) ≥ 60× 109/L; hemoglobin content (HGB) ≥ 8.0 g/dL; ② Liver function: aspartate transferase (AST) ≤ 2.5x ULN; alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum total bilirubin (TBIL) ≤ 1.5 x ULN (except Gilbert syndrome total bilirubin ≤ 3.0 mg/dL); ③ Renal function: serum creatinine ≤ 1.5 x ULN or creatinine clearance rate (CrCl) ≥ 50 mL/minute; ④ Coagulation function: international normalized ratio (INR) ≤ 1.5 x ULN, activated partial thromboplastin time (APTT) ≤ 1.5 x ULN (only for patients who are not currently receiving anticoagulant therapy, patients who are currently receiving anticoagulant therapy should receive a steady dose of anticoagulant therapy)
• The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with the follow-up

You may not qualify if:

• Pathological types of other non-hepatocellular carcinomas, including fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc. previously confirmed by histology/cytology
• Child-Pugh grade of liver function ≥7 points
• Major cardiovascular impairment in the 6 months prior to initial administration of the drug, such as a New York Heart Association (NYHA) Class II or higher history of congestive heart failure, unstable angina, myocardial infarction or stroke, or arrhythmia associated with hemodynamic instability; Corrected QT (QTc) interval lengthening \>480ms
• Other malignancies developed ≤ 5 years before the first dose, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery (hormone therapy for non-metastatic prostate cancer or breast cancer is allowed)
• Have had an active autoimmune disease in the past 2 years that requires systemic treatment, including but not limited to autoimmune hepatitis, lupus erythematosus, etc
• Uncontrolled active infection, such as active tuberculosis, HIV infection, etc.; Patients with HBV-DNA replication level below 10000IU/mL and continuous oral antiviral therapy could be enrolled.
• Had undergone major surgery in the 28 days prior to randomization or planned to undergo major surgery during the study period
• Use of live attenuated vaccine within 28 days prior to randomization, or anticipated use of such live attenuated vaccine during the study period (patients are not allowed to receive live attenuated influenza vaccine 4 weeks prior to randomization, during treatment, and within 5 months after the final administration of adbelizumab)
• Received any other investigational drug treatment or participated in another interventional clinical study within 4 weeks prior to signing the ICF
• Use of corticosteroids (\> 10 mg/ day prednisone or equivalent dose) or other immunosuppressants within ≤ 14 days prior to the first dose of the study drug. Allowing inhaled or topical use of steroids and adrenal replacement steroids in the absence of active autoimmune disease; Patients received systemic immunosuppressive drugs (including but not limited to glucocorticoids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] drugs) within 1 week prior to randomization. Patients receiving short-term, systemic immunosuppressant therapy, such as glucocorticoids for nausea, vomiting, or anaphylaxis management or prevention, may be enrolled in the study after investigator review. To allow the use of inhaled corticosteroids in patients with chronic obstructive pulmonary disease, corticosteroids such as fluhydrocortisone in patients with postural hypotension, and low-dose glucocorticoid supplements for adrenal insufficiency; Known mental illness, alcoholism, inability to quit smoking, drug or substance abuse
• In the investigator's judgment, the subjects have other factors that may lead to the forced termination of the study, such as non-compliance with the protocol, other serious illnesses (including mental illness) requiring combined treatment, serious laboratory abnormalities, family or social factors that may affect the safety of the subjects, or the collection of data and samples

Sponsors & Collaborators

• Nanjing Tianyinshan Hospital: lead

Study Sites (1)

China Pharmaceutical University Affiliated Nanjing Tianyinshan Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Folfox protocol; apatinib; icaritin; SHR-1701; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Chen Xun

CONTACT

+86-13851670770; mxrlwx19911990@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2025
• First Posted: March 25, 2025
• Study Start: May 22, 2025
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 15, 2028
• Last Updated: July 2, 2025

Record last verified: 2025-06

Locations

CN (1)