Hepatocellular CarcinomaNCT05573282
Observation Study of Sequential Regorafenib Plus ICIs After HAIC for Advanced Hepatocellular Carcinoma
An observational study of Hepatocellular Carcinoma, run by Sun Yat-sen University at 2 sites in China.
Trial summary
Hepatic artery infusion chemotherapy (HAIC) has shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC). Some patients can be converted to loco-regional therapies after 4-6 cycles of HAIC treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Regorafenib combine with ICIs
- Type of treatment
- Injection or infusion
- How many people
- 50 participants
- Where
- 2 sitesChina
- Study dates
- 16 Oct 2022to 1 Jan 2026
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Sequential and maintenance therapy of Regorafenib plus ICIs in andvanced HCC patients who have completed standard HAIC.
Who may be able to join
- Written informed consent must be obtained prior to any screening procedures.
- Cytohistological confirmation is required for diagnosis of HCC.
- Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer [BCLC] staging classification) hepatocellular carcinoma who have completed 4-6 cycles HAIC. Treated efficacy evaluation has confirmed that these patients are not suitable for loco-regional therapies or surgical resection.
- At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. Lesions previously treated with local therapy, such as radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy should not be selected unless progression is noted at baseline, in which case, these lesions would be considered as non-target lesions.
- Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascites controlled by diuretics is permitted in this study.
- Availability of a representative tumor tissue specimen (archival tumor tissue is allowed) at pre-screening.
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- Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance Status ≤ 2.
- Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial.
- Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to procedure:
- Hemoglobin > 100g/L
- Absolute neutrophil count >3.0 ×109/L
- Neutrophil count > 1.5 ×109/L
- Platelet count ≥ 50.0 ×109/L
- Total bilirubin < 51 μmol/L
- Alanine transaminase (ALT) and aminotransferase (AST) < 5 x upper limit of normal
- Albumin > 28 g/L
- Prothrombin time (PT)-international normalized ratio (INR) < 2.3, or PT < 6 seconds above control
- Serum creatinine < 110 μmol/L
- Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
Who cannot join
- A history of liver decompensation, such as refractory ascites, gastrointestinal bleeding, or hepatic encephalopathy; Uncontrolled complications, including but not limited to: Persistent or activity (except the HBV and HCV) infection, symptoms of congestive heart failure and uncontrolled diabetes, uncontrolled hypertension, unstable angina, uncontrolled arrhythmias, active ILD, severe chronic GI disease accompanied by diarrhea, or 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; 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]).
- Known to produce allergic or hypersensitive reactions to any study drug or any excipient thereof;
- Significant clinical gastrointestinal bleeding or a potential risk of bleeding was identified by the investigator during the 30 days prior to study entry.
- Tumors of the central nervous system, including metastatic brain tumors;
- Pregnant women or breast-feeding patients;
- Complicated with other malignant tumors:
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- Malignant tumors that have been treated for therapeutic purposes, have no known active disease for 5 years prior to the first administration of the study drug, and have a low potential risk of recurrence.
- Fully treated non-melanoma skin cancer or malignant freckle moles with no evidence of disease.
- Fully treated carcinoma in situ without evidence of disease.
- Prior to the initial dosing of the study drug, they had received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy.
- Has received anti-tumor system therapy for HCC. Non-anti-tumor purpose combined hormone therapy (e.g., hormone replacement therapy) is excluded.
- 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:
- intranasal, inhaled, topical or topical steroids. (e.g., intraarticular)
- Systemic corticosteroid therapy not exceeding 10 mg/ day of prednisone or its physiological equivalent as a prophylactic use of steroids for hypersensitivity. (e.g., CT scan pretherapy medication)
- Steroids as a prophylactic for allergic reactions.
- 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.
- Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days before randomization or first dose of drug.
- Pregnant or lactating women, or fertile men or women who do not want to use high-efficiency contraceptives, 6 months after the last dosing of study treatment, from screening to study treatment. Based on the patient's preferred and customary lifestyle, abstinence during treatment and washout is an acceptable contraceptive method.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Department of Minimally Invasive and Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center,
Guangzhou, Guangdong, 500060
Ming Zhao, MD, 86-20-87343272, zhaoming@sysucc.org.cn
- Recruiting
Sun Yat-sen University Cancer Center
Guanzhou, Guangdong, 510060
Ming Zhao, PHD, +86-20-87343272, zhaoming@sysucc.org.cn
About this study
Official title: Observation Study of Sequential Regorafenib Combined With Immunocheckpoint Inhibitors After Hepatic Artery Infusion Chemotherapy for Advanced Hepatocellular Carcinoma
Hepatic artery infusion chemotherapy (HAIC) has shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC). Some patients can be converted to loco-regional therapies after 4-6 cycles of HAIC treatment. But most of these patients still need to concern the sequential treatment after standard HAIC treatment (4-6 cycles). Combination of anti-angiogenic molecular targeted therapy and immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in HCC. Regorafenib is one of the standard second-line systemic therapy for advanced HCC. In this study, we will evaluate the efficacy and safety of sequential therapies of Regorafenib plus ICI in patients with advanced HCC who have completed 4-6 cycles of HAIC.
Read the detailed description
The standard procedure for HAIC is that femoral artery puncture and catheterization are performed in every cycle of treatment, a micro-catheter is inserted and located in feeding hepatic artery. The therapeutic scheme is modified FOLFOX6 regimens including oxaliplatin, leucovorin and Fluorouracil. All chemo-drugs are given by HAI. A total of 4-6 cycles of HAIC are performed and the treated efficacy is evaluated. Patient who is not suitable for loco-regional therapies after 4-6cycles of HAIC becomes to the candidate of sequential therapies of regorafenib plus ICIs. The regorafenib 80 mg/day was uses in sequential treatment. And ICIs were used intravenously at the standard dose. Patients received sequential treatment will begin no earlier than 30 days following the last HAIC procedure.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Regorafenib combine with ICIs
- Keywords
- Hepatic arterial infusion chemotherapy, Regorafenib, Immunocheckpoint inhibitor
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib combine with ICIsOther
Regorafenib: 80mg/day, PO, QD, d1～d21, Q4W ICIs: 200mg/day, IV, d1,Q3W
| Study group | Role | What they receive |
|---|---|---|
| Sequential therapy of Regorafenib combined with ICIs | Sequential therapy of Regorafenib combined with one kind of ICIs after standard HAIC treatment in advanced hepatocellular carcinoma (HCC).
ICIs: atezolizumab, pembrolizumab, nivolumab, camrelizumab, tislelizumab, sintilimab or other ICIs. Receives: Other: Regorafenib combine with ICIs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Absence of death of any cause
Measured: 2-years Followed up
Progress Free Survival
Absence of disease progression other than death
Measured: 2-years Followed up
Secondary outcomes (3)
Tumor local control
Absence of regrowth inside the treated lesion
Measured: 2-years Followed up
Adverse Events (AEs)
Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0
Measured: 2-years Followed up
Tumor Response
Tumor response to Regorafenib Combined With ICIs according to RECIST 1.1
Measured: 2-years Followed up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2022
- Study start16 Oct 2022
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Jan 2026 (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.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ming Zhao, Sun Yat-sen University
- Investigators
- Ming Zhao, M.D. & Ph.D., Principal investigator, Department of Minimally Invasive and Interventional Radiology, Liver Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05573282
- Sponsor's protocol ID
- B2022-334-01
- Status last verified
- Oct 2022
- First submitted
- 7 Oct 2022
- Last updated
- 18 Oct 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lyu N, Wang X, Li JB, Lai JF, Chen QF, Li SL, Deng HJ, He M, Mu LW, Zhao M. Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1). J Clin Oncol. 2022 Feb 10;40(5):468-480. doi: 10.1200/JCO.21.01963. Epub 2021 Dec 14.
PubMed 34905388Lyu 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 29471013Lyu N, Lin Y, Kong Y, Zhang Z, Liu L, Zheng L, Mu L, Wang J, Li X, Pan T, Xie Q, Liu Y, Lin A, Wu P, Zhao M. FOXAI: a phase II trial evaluating the efficacy and safety of hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin for advanced hepatocellular carcinoma. Gut. 2018 Feb;67(2):395-396. doi: 10.1136/gutjnl-2017-314138. Epub 2017 Jun 7. No abstract available.
PubMed 28592441
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observation Study of Sequential Regorafenib Combined With Immunocheckpoint Inhibitors After Hepatic Artery Infusion Chemotherapy for Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05573282
- Acronym / sponsor ID
- B2022-334-01
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatic arterial infusion chemotherapy, Regorafenib, Immunocheckpoint inhibitor
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 16 Oct 2022 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 10 Oct 2022 (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.
Hepatic artery infusion chemotherapy (HAIC) has shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC). Some patients can be converted to loco-regional therapies after 4-6 cycles of HAIC treatment. But most of these patients still need to concern the sequential treatment after standard HAIC treatment (4-6 cycles). Combination of anti-angiogenic molecular targeted therapy and immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in HCC. Regorafenib is one of the standard second-line systemic therapy for advanced HCC. In this study, we will evaluate the efficacy and safety of sequential therapies of Regorafenib plus ICI in patients with advanced HCC who have completed 4-6 cycles of HAIC.
Detailed description
The standard procedure for HAIC is that femoral artery puncture and catheterization are performed in every cycle of treatment, a micro-catheter is inserted and located in feeding hepatic artery. The therapeutic scheme is modified FOLFOX6 regimens including oxaliplatin, leucovorin and Fluorouracil. All chemo-drugs are given by HAI. A total of 4-6 cycles of HAIC are performed and the treated efficacy is evaluated. Patient who is not suitable for loco-regional therapies after 4-6cycles of HAIC becomes to the candidate of sequential therapies of regorafenib plus ICIs. The regorafenib 80 mg/day was uses in sequential treatment. And ICIs were used intravenously at the standard dose. Patients received sequential treatment will begin no earlier than 30 days following the last HAIC procedure.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sequential therapy of Regorafenib combined with ICIs | – | Other: Regorafenib combine with ICIsSequential therapy of Regorafenib combined with one kind of ICIs after standard HAIC treatment in advanced hepatocellular carcinoma (HCC). ICIs: atezolizumab, pembrolizumab, nivolumab, camrelizumab, tislelizumab, sintilimab or other ICIs. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Sequential and maintenance therapy of Regorafenib plus ICIs in andvanced HCC patients who have completed standard HAIC.
Key inclusion criteria (19 listed)
- Written informed consent must be obtained prior to any screening procedures.
- Cytohistological confirmation is required for diagnosis of HCC.
- Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer [BCLC] staging classification) hepatocellular carcinoma who have completed 4-6 cycles HAIC. Treated efficacy evaluation has confirmed that these patients are not suitable for loco-regional therapies or surgical resection.
- At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. Lesions previously treated with local therapy, such as radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy should not be selected unless progression is noted at baseline, in which case, these lesions would be considered as non-target lesions.
- Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascites controlled by diuretics is permitted in this study.
Key exclusion criteria (18 listed)
- A history of liver decompensation, such as refractory ascites, gastrointestinal bleeding, or hepatic encephalopathy; Uncontrolled complications, including but not limited to: Persistent or activity (except the HBV and HCV) infection, symptoms of congestive heart failure and uncontrolled diabetes, uncontrolled hypertension, unstable angina, uncontrolled arrhythmias, active ILD, severe chronic GI disease accompanied by diarrhea, or 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; 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]).
- Known to produce allergic or hypersensitive reactions to any study drug or any excipient thereof;
- Significant clinical gastrointestinal bleeding or a potential risk of bleeding was identified by the investigator during the 30 days prior to study entry.
- Tumors of the central nervous system, including metastatic brain tumors;
- Pregnant women or breast-feeding patients;
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 |
|---|---|---|
| Regorafenib combine with ICIsRegorafenib: 80mg/day, PO, QD, d1～d21, Q4W ICIs: 200mg/day, IV, d1,Q3W | Other | Sequential therapy of Regorafenib combined with ICIs |
Primary outcome
Overall Survival
Time frame: 2-years Followed up
Absence of death of any cause
Progress Free Survival
Time frame: 2-years Followed up
Absence of disease progression other than death
3 secondary outcomes
Tumor local control
Time frame: 2-years Followed up
Adverse Events (AEs)
Time frame: 2-years Followed up
Tumor Response
Time frame: 2-years Followed up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2022.
- Background: PubMed 34905388Lyu N, Wang X, Li JB, Lai JF, Chen QF, Li SL, Deng HJ, He M, Mu LW, Zhao M. Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1). J Clin Oncol. 2022 Feb 10;40(5):468-480. doi: 10.1200/JCO.21.01963. Epub 2021 Dec 14.
- Background: PubMed 29471013Lyu 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.
- Background: PubMed 28592441Lyu N, Lin Y, Kong Y, Zhang Z, Liu L, Zheng L, Mu L, Wang J, Li X, Pan T, Xie Q, Liu Y, Lin A, Wu P, Zhao M. FOXAI: a phase II trial evaluating the efficacy and safety of hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin for advanced hepatocellular carcinoma. Gut. 2018 Feb;67(2):395-396. doi: 10.1136/gutjnl-2017-314138. Epub 2017 Jun 7. No abstract available.
- 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.
Ming Zhao, M.D. & Ph.D. principal investigator
Department of Minimally Invasive and Interventional Radiology, Liver Cancer
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma, run by Sun Yat-sen University 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 19 inclusion and 18 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 18 Oct 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ming Zhao, M.D. & Ph.D. (+86-20-87343272, zhaoming@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 2-years Followed up). The study lists 2 primary outcomes in all. 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 NCT05573282, 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 18 Oct 2022.