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Hepatocellular CarcinomaPhase 3HAICNCT06041477

Concurrently vs Sequentially Combined HAIC With Targeted and Immunotherapy in Potentially Resectable HCC

A Phase 3 study testing Oxaliplatin,calcium folinic acid, levofolinic acid, 5-FU, Concurrent Lenvatinib and Concurrent PD-1 antibody in people with Hepatocellular Carcinoma and Chemotherapy Effect, run by Sun Yat-sen University at 1 site 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
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Trial summary

The goal of this clinical trial is to compare HAIC concurrently with sequentially combined with targeted and immunotherapies in terms of efficacy and safety in patients with potentially resectable intermediate and advanced HCC (CNLC stage IIa~IIIa). Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Oxaliplatin,calcium folinic acid, levofolinic acid, 5-FU, Concurrent Lenvatinib and Concurrent PD-1 antibody
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
540 participants
Where
1 siteChina
Study dates
31 Oct 2023to Jul 2030
Phase
Phase 3
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 and ≤75 years;
  • ECOG PS score of 0~1;
  • Clinical or pathological diagnosis of hepatocellular carcinoma and meeting the stage IIa-IIIa of CNLC staging according to the relevant definitions in the 2015 edition of the Guidelines for Standardized Pathological Diagnosis of Primary Liver Cancer;
  • Not having received previous treatment against hepatocellular carcinoma;
  • Those who cannot be surgically resected after discussion by the multidisciplinary team of the participating centers , but have a potential chance of resection after conversion therapy, including: multiple tumors located in one lobe of the liver; portal vein cancer thrombus not reaching the main trunk, which can be resected together with the primary focus;
  • Laboratory tests meet the following conditions, or the following conditions can be achieved with short-term treatment:
  • Neutrophil count ≥2.0×109/L; Hemoglobin ≥ 100 g/L; Platelet count ≥ 75 × 109/L; Plasma albumin level ≥ 35 g/L; Plasma total bilirubin less than 2 times the upper limit of normal; Plasma alanine aminotransferase (ALT) less than 3 times the upper limit of normal; Plasma aspartate aminotransferase (AST) less than 3 times the upper limit of normal; Plasma creatinine less than 1.5 times the upper limit of normal; Plasma prothrombin time is normal or exceeds the upper limit of normal value by ≤ 4 seconds; Prothrombinogen international normalized ratio (INR) ≤ 2.2;
  • Patients were fully informed about the study and signed an informed consent form.

Who cannot join

  • Those with severe comorbidity including cardiac, cerebral, pulmonary, renal, and other vital organ function damage, combined with severe infections or other serious concomitant diseases (> grade 2 CTCAE Version 5.0 adverse events), who cannot tolerate the treatment;
  • Those with a history of other malignant tumors;
  • Those with a history of related drug allergy;
  • Those with known hypersensitivity to any component of the targeted and immunologic drugs to be applied;
  • Those with a history of organ transplantation;
  • Those who have received previous treatment targeting hepatocellular carcinoma (including interferon);
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  • Those with co-infection with HIV;
  • Those with drugs abuse;
  • Those who have had gastrointestinal bleeding or cardiovascular events within the last 30 days;
  • Pregnant or breastfeeding women, or women of childbearing age who do not wish to use contraception;
  • Persons with concomitant psychiatric disorders that preclude informed consent or affect acceptance of treatment;
  • Other factors that may affect patient enrollment and assessment results.

Trial locations and contacts

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

Shao Hua Li, Ph.D, M,D contact

008615088064187

lishaoh@sysucc.org.cn

Rong Ping Guo, M,D contact

008618819809988

guorp@sysucc.org.cn

China1 site, 1 recruiting

  • SUN Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

    Shao Hua Li, Ph.D, M.D, 008615088064187, lishaoh@sysucc.org.cn

    Wei Wei, Ph.D, M.D, 008613725208259, weiwei@sysucc.org.cn

    Recruiting

Other trials in China

About this study

Official title: A Randomized Controlled Study of the Efficacy of Hepatic Arterial Perfusion Chemotherapy Concurrently Compared to Sequentially Combined With Targeted and Immunotherapy in Potentially Resectable Intermediate and Advanced HCC

The goal of this clinical trial is to compare HAIC concurrently with sequentially combined with targeted and immunotherapies in terms of efficacy and safety in patients with potentially resectable intermediate and advanced HCC (CNLC stage IIa~IIIa). The main questions it aims to answer are:

  • Does a "strong combination" regimen of three simultaneous treatments (HAIC, targeted agents and immunotherapy) definitely result in a higher surgical conversion rate and better survival benefit?
  • Can the combination of targeted and immunotherapies based on patients' response to HAIC therapy avoid over-treatment of some patients without affecting the surgical conversion rate and overall survival? Participants will be randomly assigned to receive either HAIC concurrently or sequentially combined with targeted and immunotherapies.

Researchers will compare concurrent treatment group with sequential treatment group to see if there are different in terms of the conversion resection rate, long-term survival, and safety.

Read the detailed description

Participants in the concurrent treatment group will receive two cycles of HAIC (the drugs are oxaliplatin 135mg/m2 over 3hrs, calcium folinic acid 400mg/m2 or levofolinic acid 200mg/ m2 over 1.5hrs, 5-FU 400mg/m2 over 2hrs, 5-FU 2400mg/m2 over 46hrs,every 4 weeks) in combination with targeted drug (lenvatinib 8mg/day) and immunotherapy (PD-1 antibody, dosage and frequency according to instructions), then evaluate the response of tumor, those who achieve complete response (CR) will receive surgical resection or follow-up, those with partial response (PR) or stable disease (SD) continue two cycles of combined therapy, and those with progress disease (PD) will be withdrawn and receive other treatments. After four cycles of combined therapy, second evaluation of efficacy will be performed, those who achieve CR will receive surgical resection or follow-up observation, and the other patients will be evaluated for the possibility of surgical resection or the subsequent treatment.

Participants in the sequential treatment group will receive two cycles of HAIC (drugs of oxaliplatin 135 mg/m2 over 3 hours; calcium folinic acid 400 mg/m2 or levofolinic acid 200 mg/m2 over 1. 5 hours, 5-FU 400 mg/m2 over 2 hours, and 5-FU 2400 mg/m2 over 46 hours,every 4 weeks), then evaluate the response of tumor, and those who achieve complete response (CR ) will receive surgical resection or follow-up, while other patients continue to receive two cycles of combination therapy, i.e. HAIC combined with targeted drug (levatinib 8mg/day) and immunotherapy (PD-1 antibody, dose and frequency according to instructions). After four cycles, a second efficacy assessment will be performed, and patients who achieve CR will undergo surgical resection or follow-up observation, and the other patients will be evaluated for the possibility of surgical resection or the subsequent treatment.

Being tested
Oxaliplatin,calcium folinic acid, levofolinic acid, 5-FU, Concurrent Lenvatinib, Concurrent PD-1 antibody, Sequential Lenvatinib, Sequential PD-1 antibody
Keywords
Hepatic artery infusion chemotherapy, Tyrosine kinase inhibitors, Immune checkpoint inhibitors, Intermediate and advanced stage hepatocellular carcinoma, combined therapy, conversion resection
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • Oxaliplatin,calcium folinic acid, levofolinic acid, 5-FUDrug

    Also called Hepatic arterial infusion chemotherapy (HAIC)

    Hepatic arterial infusion chemotherapy with (oxaliplatin 135mg/m2 over 3hrs, calcium folinic acid 400mg/m2 or levofolinic acid 200mg/ m2 over 1.5hrs, 5-FU 400mg/m2 over 2hrs, 5-FU 2400mg/m2 over 46hrs,every 4 weeks)

  • Concurrent LenvatinibDrug

    Also called Concurrent targeted therapy

    Lenvatinib 8mg/day combined with the HAIC from the first cycle

  • Concurrent PD-1 antibodyDrug

    Also called Concurrent immunotherapy

    PD-1 antibody which is approved by authorities for HCC treatment combined with the HAIC from the first cycle (dosage and frequency according to instructions)

  • Sequential LenvatinibDrug

    Also called Sequential targeted therapy

    Lenvatinib 8mg/day combined with the HAIC from the third cycle for those patients who do not achieve complete response (CR)

  • Sequential PD-1 antibodyDrug

    Also called Sequential immunotherapy

    PD-1 antibody which is approved by authorities for HCC treatment combined with the HAIC from the third cycle for those patients who do not achieve complete response (CR) (dosage and frequency according to instructions)

Study groups in NCT06041477
Study groupRoleWhat they receive
concurrent treatment groupExperimentalParticipants receive two cycles of HAIC (the drugs are oxaliplatin 135mg/m2 over 3hrs, calcium folinic acid 400mg/m2 or levofolinic acid 200mg/ m2 over 1.5hrs, 5-FU 400mg/m2 over 2hrs, 5-FU 2400mg/m2 over 46hrs,every 4 weeks) in combination with targeted drug (lenvatinib 8mg/day) and immunotherapy (PD-1 antibody, dosage and frequency according to instructions), then evaluate the response of tumor, those who achieve complete response (CR) will receive surgical resection or follow-up, those with partial response (PR) or stable disease (SD) continue two cycles of combined therapy, and those with progress disease (PD) will be withdrawn and receive other treatments. After four cycles of combined therapy, second evaluation of efficacy will be performed, those who achieve CR will receive surgical resection or follow-up observation, and the other patients will be evaluated for the possibility of surgical resection or the subsequent treatment.
Receives: Drug: Oxaliplatin,calcium folinic acid, levofolinic acid, 5-FU; Drug: Concurrent Lenvatinib; Drug: Concurrent PD-1 antibody
sequential treatment groupActive comparatorParticipants receive two cycles of HAIC (drugs of oxaliplatin 135 mg/m2 over 3 hours; calcium folinic acid 400 mg/m2 or levofolinic acid 200 mg/m2 over 1. 5 hours, 5-FU 400 mg/m2 over 2 hours, and 5-FU 2400 mg/m2 over 46 hours,every 4 weeks), then evaluate the response of tumor, and those who achieve complete response (CR ) will receive surgical resection or follow-up, while other patients continue to receive two cycles of combination therapy, i.e. HAIC combined with targeted drug (levatinib 8mg/day) and immunotherapy (PD-1 antibody, dose and frequency according to instructions). After four cycles, a second efficacy assessment will be performed, and patients who achieve CR will undergo surgical resection or follow-up observation, and the other patients will be evaluated for the possibility of surgical resection or the subsequent treatment.
Receives: Drug: Oxaliplatin,calcium folinic acid, levofolinic acid, 5-FU; Drug: Sequential Lenvatinib; Drug: Sequential PD-1 antibody

What is being measured

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

  1. OS

    Overall survival of the participants

    Measured: From date of randomization until the date of death from any cause, assessed at least 36 months

Secondary outcomes (5)

  1. PFS

    Progression-free survival of the participants

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed at least 36 months

  2. ORR

    Objective response rates, which means the proportion of patients with efficacy assessment of complete response and partial response for the size of intrahepatic target lesions according to mRECIST criteria and RECIST v1.1 criteria respectively.

    Measured: Assessed at the end of Cycle 2 and Cycle 4 (each cycle is 28 days)

  3. DCR

    Disease control rates, which means the proportion of patients with efficacy assessment of complete response, partial response and stable disease for the size of intrahepatic target lesions according to mRECIST criteria and RECIST v1.1 criteria respectively.

    Measured: Assessed at the end of Cycle 2 and Cycle 4 (each cycle is 28 days)

  4. CRR

    Conversion resection rate refer to the proportion of patients in both groups who actually underwent subsequent surgical resection.

    Measured: This outcome measure will be assessed at the end of Cycle 4 (each cycle is 28 days)

  5. Safety profiles of all participants

    Adverse Events and Severe Adverse Events evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

    Measured: This outcome measure will be assessed at the end of Cycle 1 to 4(each cycle is 28 days), and every 3 months through study completion, an average of 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 posted18 Sep 2023
  2. Study start31 Oct 2023
  3. Primary completionJul 2027 (estimated)
  4. Study completionJul 2030 (estimated)

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
540 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06041477
Sponsor's protocol ID
SL-B2022-793-01
Other IDs
2023001
Acronym
HAIC
Status last verified
Aug 2024
First submitted
23 Jul 2023
Last updated
27 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: From the perspective of protecting the privacy of participants, there was no participant data (IPD) plan in this study.

Publications

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

    PubMed 33538338

  • Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, Kudo M, Johnson P, Wagner S, Orsini LS, Sherman M. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 2015 Sep;35(9):2155-66. doi: 10.1111/liv.12818. Epub 2015 Mar 25.

    PubMed 25752327

  • Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018 Mar 31;391(10127):1301-1314. doi: 10.1016/S0140-6736(18)30010-2. Epub 2018 Jan 5.

    PubMed 29307467

  • Schwartz JD, Schwartz M, Mandeli J, Sung M. Neoadjuvant and adjuvant therapy for resectable hepatocellular carcinoma: review of the randomised clinical trials. Lancet Oncol. 2002 Oct;3(10):593-603. doi: 10.1016/s1470-2045(02)00873-2.

    PubMed 12372721

  • Shi HY, Wang SN, Wang SC, Chuang SC, Chen CM, Lee KT. Preoperative transarterial chemoembolization and resection for hepatocellular carcinoma: a nationwide Taiwan database analysis of long-term outcome predictors. J Surg Oncol. 2014 Apr;109(5):487-93. doi: 10.1002/jso.23521. Epub 2013 Nov 30.

    PubMed 24293372

  • He M, Li Q, Zou R, Shen J, Fang W, Tan G, Zhou Y, Wu X, Xu L, Wei W, Le Y, Zhou Z, Zhao M, Guo Y, Guo R, Chen M, Shi M. Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):953-960. doi: 10.1001/jamaoncol.2019.0250.

    PubMed 31070690

  • Lyu N, Kong Y, Mu L, Lin Y, Li J, Liu Y, Zhang Z, Zheng L, Deng H, Li S, Xie Q, Guo R, Shi M, Xu L, Cai X, Wu P, Zhao M. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):60-69. doi: 10.1016/j.jhep.2018.02.008. Epub 2018 Feb 20.

    PubMed 29471013

  • He MK, Le Y, Li QJ, Yu ZS, Li SH, Wei W, Guo RP, Shi M. Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma: a prospective non-randomized study. Chin J Cancer. 2017 Oct 23;36(1):83. doi: 10.1186/s40880-017-0251-2.

    PubMed 29061175

  • Li S, Mei J, Wang Q, Guo Z, Lu L, Ling Y, Xu L, Chen M, Zheng L, Lin W, Zou J, Wen Y, Wei W, Guo R. Postoperative Adjuvant Transarterial Infusion Chemotherapy with FOLFOX Could Improve Outcomes of Hepatocellular Carcinoma Patients with Microvascular Invasion: A Preliminary Report of a Phase III, Randomized Controlled Clinical Trial. Ann Surg Oncol. 2020 Dec;27(13):5183-5190. doi: 10.1245/s10434-020-08601-8. Epub 2020 May 16.

    PubMed 32418078

  • Li SH, Mei J, Cheng Y, Li Q, Wang QX, Fang CK, Lei QC, Huang HK, Cao MR, Luo R, Deng JD, Jiang YC, Zhao RC, Lu LH, Zou JW, Deng M, Lin WP, Guan RG, Wen YH, Li JB, Zheng L, Guo ZX, Ling YH, Chen HW, Zhong C, Wei W, Guo RP. Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study. J Clin Oncol. 2023 Apr 1;41(10):1898-1908. doi: 10.1200/JCO.22.01142. Epub 2022 Dec 16.

    PubMed 36525610

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oxaliplatin,calcium folinic acid, levofolinic acid, 5-FU, Concurrent Lenvatinib and Concurrent PD-1 antibody in people with Hepatocellular Carcinoma and Chemotherapy Effect, run by Sun Yat-sen University at 1 site 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 8 inclusion and 12 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 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Shao Hua Li, Ph.D, M,D (008615088064187, lishaoh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

OS (time frame: From date of randomization until the date of death from any cause, assessed at least 36 months). 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 NCT06041477, which also lists 10 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 27 Aug 2024.

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