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Hepatocellular Carcinoma Non-resectableCCGLC-001NCT05713994

Combined HAIC, TKI/Anti-VEGF and ICIs as Conversion Therapy for Unresectable Hepatocellular Carcinoma

An observational study of Hepatocellular Carcinoma Non-resectable, run by Ze-yang Ding, MD at 2 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This study is conducted to evaluate the efficacy, prognosis, adverse effects, and factors for predicting therapeutic effects and clinical prognosis of combined therapy of hepatic artery infusion chemotherapy (HAIC), tyrosine kinase inhibitor/ anti-VEGF antibody, and anti-PD-1/ PD-L1 antibody for advanced… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma Non-resectable
What is being tested?
HAIC, Bevacizumab plus Atezolizumab and Bevacizumab Biosimilar IBI305 plus sintilimab
How many people
300 participants
Where
2 sitesChina
Study dates
19 May 2020to 30 Dec 2025
Phase
Observational
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients with advanced hepatocellular carcinoma which initially unsuitable for the radical therapy, including resection, transplantation, or ablation.

Who may be able to join

  • Age ≥ 18 years old;
  • Diagnosis of HCC is according to the American Association for the Study of Liver Diseases or European Association for the Study of the Liver guidelines of HCC management;
  • at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or mRESIST criteria;
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
  • Hepatocellular carcinoma (HCC) was assessed as not suitable for radical resection, liver transplant, or ablation treatment after the assessment of a multidisciplinary team because either: (1) R0 resection was not feasible; (2) remnant liver volume was less than 30% in patients who did not have cirrhosis or 40% in patients with cirrhosis, or the results of an indocyanine green test were higher than 15%; (3) patients had Barcelona Clinic Liver Cancer (BCLC) stage B and beyond Up-to-seven criteria; or (4) patients had BCLC stage C.
  • Portal vein involvement (Chen's groups A and B, or Cheng's type I-III) is allowed: Chen's group A1 or Cheng's type I, tumor thrombus is involved in segmental or sectoral branches of the portal vein or above; Chen's group A2 or Cheng's type II, involvement of the first branch of portal vein; Chen's group B or Cheng's type III, involvement of the main portal vein.
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  • Hepatic vein invasion (VV1 to VV2) were allowed. Patients with tumor thrombus in inferior vena cava (VV3 type, Sakamoto type 1) can be included; However, patients with inferior vena cava tumor thrombus exceeding the diaphragmatic plane (Sakamoto type II) and reaching the right atrium (Sakamoto type III) cannot be included in the study;
  • Patients with extrahepatic oligometastasis is allowed: extrahepatic oligometastasis was defined as up to three metastatic lesions in up to two organs with the largest diameter of 3 cm
  • Child-Pugh liver function class A-B7
  • No prior transplantation, TACE, or radioembolization to the liver was allowed. Prior locoregional therapies, such as surgical resection, radiotherapy, radiofrequency ablation, percutaneous ethanol injection or cryoablation, are allowed if the disease have progressed since prior treatment. Local therapy must have been completed at least 4 weeks prior to the baseline scan.
  • Adequate organ and marrow function, as defined below:
  • Hemoglobin≥80 g/L; (2) Absolute neutrophil count ≥1.5 ×10^9/L; (3) Platelet count ≥50 ×10^9/L; (4) Total bilirubin < 51 μmol/L; (5) Alanine transaminase (ALT) and aminotransferase (AST)≤5×ULN; (6) Albumin ≥28 g/L; (7) INR ≤1.6; (8) Serum creatinine < 110 μmol/L.

Who cannot join

  • Prior invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured
  • Severe, active and uncontrolled co-morbidity including but not limited to:
  • Persistent or activity (except the HBV and HCV) infection; (2) symptoms of congestive heart failure and uncontrolled diabetes; (3) uncontrolled hypertension, systolic pressure≥160 mmHg or diastolic pressure≥100 mmHg despite anti-hypertension medications≤28 days before randomization or first dose of drug; (4) unstable angina; (5) uncontrolled arrhythmias; (6) active ILD; (7) severe chronic GI disease accompanied by diarrhea; (8) compliance with requirements may limit the research, resulted in significant increase risk of AE or influence Subjects provided psychiatric/social problem status on their ability to provide written informed consent; (9) A history of active primary immunodeficiency or human immunodeficiency virus; (10) Active or previous records of autoimmune disease or inflammatory diseases, including inflammatory bowel disease (e.g., colitis or Crohn's disease], diverticulitis, except [diverticulosis], systemic lupus erythematosus (SLE), sarcoidosis syndrome or Wegener syndrome (e.g., granulomatous vasculitis, gray's disease, rheumatoid arthritis, the pituitary gland inflammation and uveitis]); (11) A history of hepatic decompensation, including refractory ascites, gastrointestinal bleeding, or hepatic encephalopathy.
  • 3. Known to produce allergic or hypersensitive reactions to any study drug or any excipient thereof.
  • 4. Significant clinical gastrointestinal bleeding or a potential risk of bleeding was identified by the investigator during the 30 days prior to study entry.
  • 5. Tumors of the central nervous system, including metastatic brain tumors. 6. Pregnant women or breast-feeding patients. 7. Has received anti-tumor system therapy for HCC. Non-anti-tumor purpose combined hormone therapy (e.g., hormone replacement therapy) is excluded.
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  • 8. Is currently using, or has used an immunosuppressive drug within 14 days prior to the first dose of the investigational drug. This standard has the following exceptions: (1) intranasal, inhaled, topical or topical steroids. (e.g., intraarticular); (2) Systemic corticosteroid therapy not exceeding 10 mg/ day of prednisone; (3) prophylactic use of steroids for hypersensitivity. (e.g., CT scan pretherapy medication).
  • 9. A live attenuated vaccine was administered within 30 days prior to the first administration of the study drug. Note: If enrolled, patients shall not receive live attenuated vaccine within 30 days of receiving study drug therapy and after the last administration of study drug.
  • 10. Extrahepatic vascular involvement or thrombosis: superior mesenteric vein (Cheng's type IV), or with inferior vena cava tumor thrombus exceeding the diaphragmatic plane (Sakamoto type II) or reaching the right atrium (Sakamoto type III) cannot be included in the study.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

ZeYang Ding, M.D. contact

+86-13407156200

dingzyang@sina.com

China2 sites, 2 recruiting

  • The Second Affiliated Hospital of Fujian Medical University

    Quanzhou, Fujian, 362000

    Yan-jun Wang, M.D., +15872415556, wangyanjun@fjmu.edu.cn

    Recruiting

  • TongjiHospital

    Wuhan, Hubei, 430000

    Ze-yang Ding, M.D., 13407156200, dingzyang@sina.com

    Jianping Zhao, M.D.

    Recruiting

Other trials in China

About this study

Official title: Combined Hepatic Arterial Infusion Chemotherapy, Tyrosine Kinase Inhibitor/ Anti-VEGF Antibody, and Anti-PD-1/ PD-L1 Antibody as Conversion Therapy for Unresectable Hepatocellular Carcinoma

This study is conducted to evaluate the efficacy, prognosis, adverse effects, and factors for predicting therapeutic effects and clinical prognosis of combined therapy of hepatic artery infusion chemotherapy (HAIC), tyrosine kinase inhibitor/ anti-VEGF antibody, and anti-PD-1/ PD-L1 antibody for advanced hepatocellular carcinoma which initially unsuitable for the radical therapy, including resection, transplantation, or ablation. Factors are collected in preoperative routine blood examination, preoperative radiological imaging and pathological examination.

Read the detailed description

As a local interventional treatment, hepatic arterial infusion chemotherapy (HAIC) has shown better efficacy and safety than traditional transcatheter arterial chemoembolization (TACE) in the treatment of unresectable HCC. In addition, HAIC has been widely used as an alternative to sorafenib in advanced HCC in the eastern Asia. Systemic therapies such as tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), as well as the combined use of anti-VEGF antibody and ICIs have shown promising results in the treatment of advanced HCC. Numerous studies have shown that combination therapy has a trend toward better tumor response rates, survival outcomes, and downstaging rate to monotherapy.

This study is conducted by the by Chinese Collaborative Group of Liver Cancer (CCGLC), the Chinese Chapter of the International Hepato-Pancreato-Biliary Association (CC-IHPBA). It is estimated that 300 patients with advanced hepatocellular carcinoma will be enrolled in about 4 research centers. And it is planned to complete the enrollment within 1 year and it is expected that all enrolled subjects will reach the observation end point in 3 years.

Being tested
HAIC, Bevacizumab plus Atezolizumab, Bevacizumab Biosimilar IBI305 plus sintilimab, Lenvatinib, Sorafenib
Keywords
Liver Neoplasms, Hepatocellular Carcinoma
Medical subject headings
Liver Neoplasms, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HAICProcedure or surgery

    Also called hepatic arterial infusion chemotherapy of FOLFOX

    administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks.

  • Bevacizumab plus AtezolizumabDrug

    Also called Avastin plus Tecentriq

    Bevacizumab (15mg/kg, q3w) plus Atezolizumab (1200 mg, q3w)

  • Bevacizumab Biosimilar IBI305 plus sintilimabDrug

    Also called Byvasda (B) plus S

    Bevacizumab Biosimilar IBI305 (15mg/kg, q3w), and sintilimab (200 mg, q3w)

  • LenvatinibDrug

    Also called Lenvima

    8mg; p.o.; q.d.

  • SorafenibDrug

    Also called Nexavar

    400mg; p.o. bid

  • DonafenibDrug

    Also called Zepsun

    200mg; p.o. bid

  • RegorafenibDrug

    Also called stivarga

    160 mg; p.o.; q.d.

  • apatinib plus camrelizumabDrug

    Also called Apa plus C

    Apatinib(250 mg; p.o.; q. d.); camrelizumab (200 mg; iv drip; q2w)

  • Anti-PD-1 monoclonal antibodyDrug

    Also called PD-1 inhibitor

    HCC Patients treated with TKI plus anti-PD-1 monoclonal antibody as systemic therapy were recruited. Anti-PD-1 monoclonal antibodies include pembrolizumab (200 mg, q3w), nivolumab (3mg/kg, q2w), camrelizumab (200mg, q2w), tislelizumab (200mg, q3w), sintilimab (200 mg, q3w), or toripalimab (240mg, q3w).

Study groups in NCT05713994
Study groupRoleWhat they receive
HAIC-A-T cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus bevacizumab (A) and atezolizumab (T) as conversion therapy for downstaging.
Receives: Procedure: HAIC; Drug: Bevacizumab plus Atezolizumab
HAIC-Len-ICI cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus lenvatinib (Len) and anti-PD-1 antibody as conversion therapy for downstaging.
Receives: Procedure: HAIC; Drug: Lenvatinib; Drug: Anti-PD-1 monoclonal antibody
HAIC-B-S cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus bevacizumab biosimilar (Byvasda, B) and Sintilimab (Tyvyt, S) antibody as conversion therapy for downstaging.
Receives: Procedure: HAIC; Drug: Bevacizumab Biosimilar IBI305 plus sintilimab
HAIC-Apa-C cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus Apatinib (Apa) and Camrelizumab (C) antibody as conversion therapy for downstaging.
Receives: Procedure: HAIC; Drug: apatinib plus camrelizumab
HAIC-Sor-ICI cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus sorafenib (Sor) and anti-PD-1 antibody as conversion therapy for downstaging.
Receives: Procedure: HAIC; Drug: Sorafenib; Drug: Anti-PD-1 monoclonal antibody
HAIC-Don-ICI cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus donafenib (Don) and anti-PD-1 antibody as conversion therapy for downstaging.
Receives: Procedure: HAIC; Drug: Donafenib; Drug: Anti-PD-1 monoclonal antibody
HAIC-Reg-ICI cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus regorafenib (Reg) and anti-PD-1 antibody as conversion therapy for downstaging.
Receives: Procedure: HAIC; Drug: Regorafenib; Drug: Anti-PD-1 monoclonal antibody

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Amendable to Curative Surgical Interventions

    Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection, transplantation, or ablation after successful down-sizing of tumor(s) by intervention.

    Measured: from the date of first treatment to the date of last treatment, an average of 3 years

Secondary outcomes (10)

  1. overall response rate (ORR) measured by mRECIST criteria

    Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions; Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease; Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.

    ORR=CR+PR.

    Measured: rom the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years

  2. Time to progression (TTP)

    Time to progression (TTP): measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1. This does not include death from any cause.

    Measured: from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years

  3. Time to intrahepatic tumor progression (TTITP)

    Time to intrahepatic tumor progression (TTITP): measured from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST 1.1. This does not include death from any cause.

    Measured: from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST, assessed up to 3 years

  4. Progression-free survival (PFS)

    measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.

    Measured: from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years

  5. Overall survival (OS)

    Overall survival (OS): measured from date of first treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.

    Measured: from the date of first treatment to the date of death from any cause, assessed up to 5 years

  6. Incidence of Study-Related Adverse Events

    Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI-CTCAE 5.0)

    Measured: from the date of first treatment to 90 days after last treatment, around 3 years and 90 days

  7. Pathological response

    Pathological response is assessed as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used.

    Measured: from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 5 years

  8. Disease control rate (DCR)

    Percentage of patients that had a CR, PR, or SD ≥ 6 months per mRECIST

    Measured: from the date of first treatment to radiographically documented response according to mRECIST, assessed up to 3 years

  9. Duration of response

    Defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression (PD) or death from any cause

    Measured: from the date of first documented evidence of CR or PR to first documented sign of PD or death from any cause according to mRECIST 1.1, assessed up to 3 years

  10. Quality of Life (QoL) after treatment

    The life quality of every subject is assessed every 3 months during follow up according to the 45-item FACT-Hep questionnaire, which assesses generic HRQL concerns and disease-specific issues.

    Measured: assessed form the date of first followup to radiographically documented progression or or death from any cause, up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2023
  2. Study start19 May 2020
  3. Primary completion30 Jun 2025 (estimated)
  4. Study completion30 Dec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05713994
Sponsor's protocol ID
2020-S205
Acronym
CCGLC-001
Status last verified
Mar 2025
First submitted
16 Jan 2023
Last updated
25 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Mazzaferro V, Citterio D, Bhoori S, Bongini M, Miceli R, De Carlis L, Colledan M, Salizzoni M, Romagnoli R, Antonelli B, Vivarelli M, Tisone G, Rossi M, Gruttadauria S, Di Sandro S, De Carlis R, Luca MG, De Giorgio M, Mirabella S, Belli L, Fagiuoli S, Martini S, Iavarone M, Svegliati Baroni G, Angelico M, Ginanni Corradini S, Volpes R, Mariani L, Regalia E, Flores M, Droz Dit Busset M, Sposito C. Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial. Lancet Oncol. 2020 Jul;21(7):947-956. doi: 10.1016/S1470-2045(20)30224-2.

    PubMed 32615109

  • Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

    PubMed 32402160

Questions about this trial

What is this clinical trial studying?

An observational study of Hepatocellular Carcinoma Non-resectable, run by Ze-yang Ding, MD at 2 sites 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 12 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact ZeYang Ding, M.D. (+86-13407156200, dingzyang@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Amendable to Curative Surgical Interventions (time frame: from the date of first treatment to the date of last treatment, an average of 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05713994, which also lists 2 linked publications.

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 25 Mar 2025.

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