Hepatocellular CarcinomaPhase 2NCT04994236
Hepatic Artery Infusion Chemotherapy for Unresectable Hepatocelluar Carcinoma Who Failed to Systemic Therapy
A Phase 2 study testing Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin) in people with Hepatocellular Carcinoma, run by Hui-Chuan Sun at 1 site in China.
Trial summary
There are limited treatment options for patients with unresectable hepatocellular carcinoma (HCC) who failed to the combination therapy with targeted agents plus anti-PD-1/PD-L1. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2021to 31 Dec 2022
- Phase
- Phase 2
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hepatocellular carcinoma diagnosed histologically/cytologically, or meeting the clinical diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition)."
- Unresectable or advanced hepatocellular carcinoma that was assessed by the investigator. Advanced hepatocellular carcinoma was defined as BCLC C stage or Chinese Liver Cancer stage (CNLC) IIIa or IIIb stage.
- Had at least one measurable lesion in the liver.
- Liver function Child-Pugh classification of A or B7.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Patients who have received combination therapy with targeted agents combined with immune checkpoint inhibitors and have developed intolerable adverse effects or imaging confirmed intrahepatic tumor progression and have signed an informed consent form. Targeted agents include sorafenib, lenvatinib, donafenib, regorafenib, apatinib, bevacizumab (or biosimilar), and anlotinib; immune checkpoint inhibitors (mainly PD-1/PD-L1 antibodies) include pembrolizumab, nivolumab, camrelizumab, sintilimab, toripalimab, atezolizumab, and tislelizumab. Additional eligible subjects: subjects who have received at least one HAIC treatment were entered into safety evaluation (SAS); subjects who have received at least one imaging evaluation after treatment were entered into effectiveness evaluation (ITT).
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- Adequate bone marrow and organ function. Reassessment of bone marrow and organ function as described above is required prior to each HAIC treatment.
- Leukocytes ≥ 3 x 10^9/L within the last 14 days.
- Platelets ≥ 50×10^9/L in the last 14 days without transfusion.
- hemoglobin ≥ 90 g/L in the last 14 days without blood transfusion or erythropoietin administration.
- total bilirubin ≤ 2 x the upper limit of normal (ULN)
- albumin ≥ 30 g/L in the absence of human albumin or plasma transfusion within the last 14 days
- AST and ALT ≤ 3 x ULN.
- serum creatinine at ≤1.5×ULN.
- International Normalized Ratio (INR) of prothrombin time ≤ 1.5×ULN.
- Serum HBV DNA < 2 x 10^3 IU/mL; for HBV DNA > 2 x 10^3 IU/mL, treatment with nucleoside analogs for at least 1 week.
- Without grade 3 or higher adverse events (NCI CTCAE 4.0 criteria) induced by previous systemic therapy, or grade 3 or higher events reactions have recovered to grade 2 or lower.
Who cannot join
- Pathologic diagnosed with mixed liver cancer, fibrous lamellar cell carcinoma or other non-hepatocellular malignancy component.
- Previous or concurrent other malignancies, except adequately treated non-melanotic skin cancer, carcinoma in situ of the cervix, and papillary thyroid cancer
- History of organ transplantation or hepatic encephalopathy.
- Hypersensitivity to iodine-containing contrast agents, oxaliplatin, calcium folinic acid, and fluorouracil.
- History of gastrointestinal perforation and/or fistula within 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea.
- Uncontrollable hypertension, systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg after optimal medical therapy, history of hypertensive crisis or hypertensive encephalopathy.
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- Gastrointestinal bleeding due to portal hypertension within 6 months; G3 varices by gastrointestinal endoscopy within 3 months.
- Subjects requesting withdrawal of informed consent.
- Other circumstances that the investigator deems inappropriate for participation in the clinical trial.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital
Shanghai, Shanghai Municipality, 200032
Mei-Ling Li, +86 21 64041990, livercongress@zs-hospital.sh.cn
Hui-Chuan Sun
About this study
Official title: Efficacy and Safety of Hepatic Artery Infusion Chemotherapy in Patients With Advanced or Unresectable Hepatocellular Carcinoma Who Have Progressed or Are Intolerant to Systemic Therapy
There are limited treatment options for patients with unresectable hepatocellular carcinoma (HCC) who failed to the combination therapy with targeted agents plus anti-PD-1/PD-L1. Hepatic artery infusion chemotherapy (HAIC) had shown potent antitumor effects in single-centered studies when was used as first-line therapy. However, HAIC was not used as second or third-line therapy.
Read the detailed description
The combination therapy of anti-angiogenic agents and anti-PD-1/PD-L1 antibodies had shown potent anti-tumor efficacy for unresectable or advanced hepatocellular carcinoma. However, the treatment options were limited when patients were failed the combination therapies. Hepatic artery infusion chemotherapy (HAIC) had shown potent anti-tumor efficacy with an acceptable safety profile as a first-line treatment for patients with intermediated-stage or advanced-stage hepatocellular carcinoma. In this study, the investigators aimed to evaluate the efficacy and safety of HAIC were used in the late-line setting, i.e., after the failure of combination therapy with anti-angiogenic agents and anti-PD-1/PD-L1 antibodies.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin)
- Keywords
- Hepatic artery infusion chemotherapy
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin)Drug
Also called HAIC
The FOLFOX regiments were given via hepatic artery catheterization, including oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2, followed by fluorouracil infusion 2400 mg/m2 for 46 hours. If no severe adverse events occurred, the treatment will be repeated every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Hepatic Artery Infusion Chemotherapy | Experimental | Subjects assigned to this arm will receive chemotherapy via catheterizations placed into the hepatic artery. Receives: Drug: Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response of intrahepatic lesions
Subjects with complete response or partial response assessed by RECIST v1.1 criteria.
Measured: up to 1 year
Secondary outcomes (6)
duration of response of intrahepatic lesions
the interval between the time of partial or complete response to the time of progressive disease in intrahepatic lesions.
Measured: up to 1 year
Progression free survival
the interval between the time of first HAIC treatment to the time of progressive disease or patient death
Measured: up to 1 year
Overall survival
the interval between the time of first HAIC treatment initiation to the time of patient death
Measured: up to 2 year
Treatment cycles of HAIC
the total cycles of HAIC treatments, when the subjects could not tolerate HAIC or lose the benefit from HAIC treatment, HAIC will be discontinued.
Measured: up to 1 year
Ratio of R0 resection
The ratio of subjects who underwent R0 resection to subjects received who received at least 1 cycle of HAIC.
Measured: up to 1 year
The rate of adverse events
Nature, incidence, severity and seriousness of the adverse events. Adverse events are graded according to the NCI-CTCAE (Version 5.0)
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2021
- Study start1 Jul 2021
- Primary completion31 Aug 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hui-Chuan Sun
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Hui-Chuan Sun, Shanghai Zhongshan Hospital
- Investigators
- Hui-Chuan Sun, MD&PhD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04994236
- Sponsor's protocol ID
- 2LHAIC
- Status last verified
- Aug 2021
- First submitted
- 29 Jul 2021
- Last updated
- 13 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
He MK, Liang RB, Zhao Y, Xu YJ, Chen HW, Zhou YM, Lai ZC, Xu L, Wei W, Zhang YJ, Chen MS, Guo RP, Li QJ, Shi M. Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma. Ther Adv Med Oncol. 2021 Mar 25;13:17588359211002720. doi: 10.1177/17588359211002720. eCollection 2021.
PubMed 33854567Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer. 2020 Dec;9(6):682-720. doi: 10.1159/000509424. Epub 2020 Nov 11.
PubMed 33442540Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Mamontov K, Meyer T, Kubota T, Dutcus CE, Saito K, Siegel AB, Dubrovsky L, Mody K, Llovet JM. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2020 Sep 10;38(26):2960-2970. doi: 10.1200/JCO.20.00808. Epub 2020 Jul 27.
PubMed 32716739
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Hepatic Artery Infusion Chemotherapy in Patients With Advanced or Unresectable Hepatocellular Carcinoma Who Have Progressed or Are Intolerant to Systemic Therapy
- ClinicalTrials.gov ID
- NCT04994236
- Acronym / sponsor ID
- 2LHAIC
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatic artery infusion chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 49 participants (estimated)
- Lead sponsor
- Hui-Chuan SunUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 31 Aug 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 6 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There are limited treatment options for patients with unresectable hepatocellular carcinoma (HCC) who failed to the combination therapy with targeted agents plus anti-PD-1/PD-L1. Hepatic artery infusion chemotherapy (HAIC) had shown potent antitumor effects in single-centered studies when was used as first-line therapy. However, HAIC was not used as second or third-line therapy.
Detailed description
The combination therapy of anti-angiogenic agents and anti-PD-1/PD-L1 antibodies had shown potent anti-tumor efficacy for unresectable or advanced hepatocellular carcinoma. However, the treatment options were limited when patients were failed the combination therapies. Hepatic artery infusion chemotherapy (HAIC) had shown potent anti-tumor efficacy with an acceptable safety profile as a first-line treatment for patients with intermediated-stage or advanced-stage hepatocellular carcinoma. In this study, the investigators aimed to evaluate the efficacy and safety of HAIC were used in the late-line setting, i.e., after the failure of combination therapy with anti-angiogenic agents and anti-PD-1/PD-L1 antibodies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hepatic Artery Infusion Chemotherapy | Experimental | Drug: Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin)Subjects assigned to this arm will receive chemotherapy via catheterizations placed into the hepatic artery. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Hepatocellular carcinoma diagnosed histologically/cytologically, or meeting the clinical diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition)."
- Unresectable or advanced hepatocellular carcinoma that was assessed by the investigator. Advanced hepatocellular carcinoma was defined as BCLC C stage or Chinese Liver Cancer stage (CNLC) IIIa or IIIb stage.
- Had at least one measurable lesion in the liver.
- Liver function Child-Pugh classification of A or B7.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Key exclusion criteria (9 listed)
- Pathologic diagnosed with mixed liver cancer, fibrous lamellar cell carcinoma or other non-hepatocellular malignancy component.
- Previous or concurrent other malignancies, except adequately treated non-melanotic skin cancer, carcinoma in situ of the cervix, and papillary thyroid cancer
- History of organ transplantation or hepatic encephalopathy.
- Hypersensitivity to iodine-containing contrast agents, oxaliplatin, calcium folinic acid, and fluorouracil.
- History of gastrointestinal perforation and/or fistula within 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin)Also: HAICThe FOLFOX regiments were given via hepatic artery catheterization, including oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2, followed by fluorouracil infusion 2400 mg/m2 for 46 hours. If no severe adverse events occurred, the treatment will be repeated every 3 weeks. | Drug | Hepatic Artery Infusion Chemotherapy |
Primary outcome
Objective response of intrahepatic lesions
Time frame: up to 1 year
Subjects with complete response or partial response assessed by RECIST v1.1 criteria.
6 secondary outcomes
duration of response of intrahepatic lesions
Time frame: up to 1 year
Progression free survival
Time frame: up to 1 year
Overall survival
Time frame: up to 2 year
Treatment cycles of HAIC
Time frame: up to 1 year
Ratio of R0 resection
Time frame: up to 1 year
The rate of adverse events
Time frame: up to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2021.
- Background: PubMed 33854567He MK, Liang RB, Zhao Y, Xu YJ, Chen HW, Zhou YM, Lai ZC, Xu L, Wei W, Zhang YJ, Chen MS, Guo RP, Li QJ, Shi M. Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma. Ther Adv Med Oncol. 2021 Mar 25;13:17588359211002720. doi: 10.1177/17588359211002720. eCollection 2021.
- Background: PubMed 33442540Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer. 2020 Dec;9(6):682-720. doi: 10.1159/000509424. Epub 2020 Nov 11.
- Background: PubMed 32716739Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Mamontov K, Meyer T, Kubota T, Dutcus CE, Saito K, Siegel AB, Dubrovsky L, Mody K, Llovet JM. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2020 Sep 10;38(26):2960-2970. doi: 10.1200/JCO.20.00808. Epub 2020 Jul 27.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hui-Chuan Sun, MD&PhD principal investigator
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin) in people with Hepatocellular Carcinoma, run by Hui-Chuan Sun 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 17 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: status not confirmed, as of the sponsor's last update on 13 Aug 2021. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Hui-Chuan Sun, MD&PhD (+86-21-64037181, sun.huichuan@zs-hospital.sh.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response of intrahepatic lesions (time frame: up to 1 year). 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 NCT04994236, 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 Aug 2021.