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Hepatocellular Carcinoma Non-resectableCCGLC-008NCT05717738

Combined TACE, TKI/Anti-VEGF and ICIs as Conversion Therapy for Advanced Hepatocellular Carcinoma

An observational study of Hepatocellular Carcinoma Non-resectable, run by Tongji Hospital at 4 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The aim of this study is to the efficacy, prognosis, adverse effects, and factors for predicting therapeutic effects and clinical prognosis of combined therapy of transarterial chemoembolization (TACE), Anti-VEGF antibodies or pan-target anti-angiogenic drugs, and anti-PD-1/ PD-L1 antibody for advanced hepatocellular… 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?
TACE, Lenvatinib and Anti-PD-1 monoclonal antibody
How many people
300 participants
Where
4 sitesChina
Study dates
20 Jan 2022to 31 Dec 2024
Phase
Observational
Are there results?
None posted in the registry

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 or BCLC stage C.
  • portal vein involvement (Chen's groups A, or Cheng's type I-II) 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.
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  • hepatic vein invasion (VV1 to VV2) were allowed.
  • 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 ×109/L (3) Platelet count ≥50 ×109/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 12. Time interval between TACE and systemic therapy within 7 days.

Who cannot join

  • 1. 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 2. Severe, active and uncontrolled co-morbidity including but not limited to:
  • Persistent or activity (except the HBV and HCV) infection;
  • symptoms of congestive heart failure and uncontrolled diabetes;
  • uncontrolled hypertension, systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days before randomization or first dose of drug.
  • unstable angina,
  • uncontrolled arrhythmias,
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  • active ILD,
  • severe chronic GI disease accompanied by diarrhea,
  • 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.
  • 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]).
  • 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.
  • 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: main trunk of portal vein and superior mesenteric vein (Cheng's type III and IV) or inferior vena cava (IVC) (VV3).

Trial locations and contacts

4 sites in 1 country.

Ze-yang Ding, M.D. contact

+86-13407156200

zyding@tjh.tjmu.edu.cn

China4 sites, 4 recruiting

  • The Second Affiliated Hospital of Fujian Medical University

    Quanzhou, Fujian

    Yan-jun Wang, M.D., +86-15872415556, wangyanjun@fjmu.edu.cn

    Recruiting

  • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

    Wuhan, Hubei, 430030

    Ze-yang Ding, M.D.

    Recruiting

  • Optical Valley branch of Tongji hospital

    Wuhan, Hubei, 430073

    Zhanguo Zhang, M.D.

    Recruiting

  • Sino-French branch of Tongji hospital

    Wuhan, Hubei

    Ganxun Li, M.D.

    Recruiting

Other trials in China

About this study

Official title: Combined Transarterial Chemoembolization, Tyrosine Kinase Inhibitor/ Anti-VEGF Antibody, and Anti-PD-1/ PD-L1 Antibody as Conversion Therapy for Advanced Hepatocellular Carcinoma: a Multicenters, Real-world, Ambispective Cohort Study

The aim of this study is to the efficacy, prognosis, adverse effects, and factors for predicting therapeutic effects and clinical prognosis of combined therapy of transarterial chemoembolization (TACE), Anti-VEGF antibodies or pan-target anti-angiogenic drugs, and anti-PD-1/ PD-L1 antibody for advanced hepatocellular carcinoma which initially unsuitable for the radical therapy, including resection, transplantation, or ablation.

Read the detailed description

The multicenter, non-random, open and ambispective real-world cohort study is conducted at 4 research centers, including 3 centers (Hankou, Sino-French New District, and Optical Valley) of Tongji hospital (Wuhan, China) and one in the second affiliated hospital of Fujian Medical University (Quanzhou, China). It is estimated that 300 patients with advanced HCC will be enrolled in these 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. Radiological assessments are performed every two cycles over the course of treatment, then every 3 months within the first two years following the completion of treatment and every 6 months thereafter, until PD were recorded. All subjects are followed until death or lost to follow up.

Being tested
TACE, Lenvatinib, Anti-PD-1 monoclonal antibody, Bevacizumab Biosimilar IBI305 plus sintilimab, Bevacizumab plus Atezolizumab
Keywords
Hepatocellular Carcinoma, Downstaging conversion therapy
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • TACEProcedure or surgery

    Also called transarterial chemoembolization

    Procedure of TACE is standardized.

  • LenvatinibDrug

    Also called levima

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

  • Anti-PD-1 monoclonal antibodyDrug

    Also called PD-1 inhibitor

    Advanced 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).

  • Bevacizumab Biosimilar IBI305 plus sintilimabDrug

    Also called Byvasda (B) plus S

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

  • Bevacizumab plus AtezolizumabDrug

    Also called Avastin plus Tecentriq

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

  • apatinib plus camrelizumabDrug

    Also called Apa plus C

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

  • 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.

Study groups in NCT05717738
Study groupRoleWhat they receive
TACE-Len-ICI cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus lenvatinib (Len) and anti-PD-1 antibody as conversion therapy for downstaging.
Receives: Procedure: TACE; Drug: Lenvatinib; Drug: Anti-PD-1 monoclonal antibody
TACE-A-T cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus bevacizumab (A) and atezolizumab (T) as conversion therapy for downstaging.
Receives: Procedure: TACE; Drug: Bevacizumab plus Atezolizumab
TACE-B-S cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus bevacizumab biosimilar (Byvasda, B) and Sintilimab (Tyvyt, S) antibody as conversion therapy for downstaging.
Receives: Procedure: TACE; Drug: Bevacizumab Biosimilar IBI305 plus sintilimab
TACE-Apa-C cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus Apatinib (Apa) and Camrelizumab (C) antibody as conversion therapy for downstaging.
Receives: Procedure: TACE; Drug: apatinib plus camrelizumab
TACE-Sor-ICI cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus sorafenib (Sor) and anti-PD-1 antibody as conversion therapy for downstaging.
Receives: Procedure: TACE; Drug: Anti-PD-1 monoclonal antibody; Drug: Sorafenib
TACE-Don-ICI cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus donafenib (Don) and anti-PD-1 antibody as conversion therapy for downstaging.
Receives: Procedure: TACE; Drug: Anti-PD-1 monoclonal antibody; Drug: Donafenib
TACE-Reg-ICI cohortPatients with advanced hepatocellular carcinoma who was initially evaluated unsuitable for the radical therapy and received combined TACE plus regorafenib (Reg) and anti-PD-1 antibody as conversion therapy for downstaging.
Receives: Procedure: TACE; Drug: Anti-PD-1 monoclonal antibody; Drug: Regorafenib

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. Response Rate 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.

    Response rate is the rate of CR plus PR.

    Measured: from the date of first treatment to radiographically documented progression according to mRECIST v1.1, 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 mRECIST1.1, 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 1.1, 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)

    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. Pathological complete response (pCR) is defined by the absence of viable tumor cells in any nodule.

    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 5 years.

  8. Disease control rate

    Percentage of patients that had a CR, PR, or SD ≥ 6 months per mRECIST1.1.

    Measured: from the date of first treatment to radiographically documented response according to mRECIST 1.1, 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: 3 year

Timeline

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

  1. First posted8 Feb 2023
  2. Study start20 Jan 2022
  3. Primary completion31 Dec 2023
  4. Study completion31 Dec 2024 (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
Other
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05717738
Sponsor's protocol ID
TJ-IRB-20221202
Acronym
CCGLC-008
Status last verified
Jun 2024
First submitted
29 Jan 2023
Last updated
13 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Chiang CL, Chiu KWH, Chan KSK, Lee FAS, Li JCB, Wan CWS, Dai WC, Lam TC, Chen W, Wong NSM, Cheung ALY, Lee VWY, Lau VWH, El Helali A, Man K, Kong FMS, Lo CM, Chan AC. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):169-178. doi: 10.1016/S2468-1253(22)00339-9. Epub 2022 Dec 15.

    PubMed 36529152

  • 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

  • Luo L, He Y, Zhu G, Xiao Y, Song S, Ge X, Wang T, Xie J, Deng W, Hu Z, Shan R. Hepatectomy After Conversion Therapy for Initially Unresectable HCC: What is the Difference? J Hepatocell Carcinoma. 2022 Dec 22;9:1353-1368. doi: 10.2147/JHC.S388965. eCollection 2022.

    PubMed 36578526

Questions about this trial

What is this clinical trial studying?

An observational study of Hepatocellular Carcinoma Non-resectable, run by Tongji Hospital at 4 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 14 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: status not confirmed, as of the sponsor's last update on 13 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

Results are not available in the source record.

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

Contact Ze-yang Ding, M.D. (+86-13407156200, zyding@tjh.tjmu.edu.cn), 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 NCT05717738, which also lists 3 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 13 Jun 2024.

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