Hepatocellular CarcinomaPhase 2NCT05971199
Phase II Study of Fruquintinib Combined With Sintilimab and TACE for Inoperable Primary Hepatocellular Carcinoma
A Phase 2 study testing Fruquintinib, Sintilimab and Transcatheter arterial chemoembolization（TACE） in people with Hepatocellular Carcinoma, run by Zhejiang Cancer Hospital at 1 site in China.
Trial summary
The goal of this prospective, interventional clinical trial is to evaluation of fruquintinib in combination with sintulimab and TACE for inoperable primary hepatocellular carcinoma for progression-free survival (PFS). 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?
- Fruquintinib, Sintilimab and Transcatheter arterial chemoembolization（TACE）
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteChina
- Study dates
- 23 Nov 2021to 23 Dec 2024
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years, male or female;
- Patients diagnosed with primary hepatocellular carcinoma (HCC) based on clinical diagnosis or pathology;
- Patients diagnosed with Chinese stage IIb-IIIa according to the Primary Liver Cancer Diagnostic and Treatment Protocol (2019 version), and evaluated by the investigator to be unable to undergo surgical treatment, such as resection, ablation or liver transplantation;
- Imaging reports within 14 days prior to the intervention showed the presence of at least 1 target lesion measurable by CT or MRI, and the lesion is suitable for repeated accurate measurements;
- Child-Pugh liver function rating: grade A or better B (≤7 points);
- ECOG score: 0-1;
Show all 10Show fewer
- all lesions amenable to phase 1 or 2 (fractionated TACE) TACE therapy;
- Good organ and bone marrow function. Blood count: WBC>4. 0 × 109/L, Hb>80g/L, PLT>75 ×109/L, NEUT>/ 1.5 × 109/L; coagulation function:International normalized (prothrombin time) ratio(INR) <1.2; liver function indexes: serum albumin (ALB) >3.5 g/dl, serum total bilirubin(TBIL) <1.5 times the upper limit of normal value (excluding biliary obstruction), serum transaminases (ALT and AST)<3 times the upper limit of normal value; renal function: serum myelin (CR) <1.5 times the upper limit of normal value;
- Patients with positive hepatitis B surface antigen need to have received anti-hepatitis B treatment prior to inclusion in the study;
- Signed an informed consent form, were compliant and cooperated with the follow-up.
Who cannot join
- Hepatobiliary cell carcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma and fibrous lamellar hepatocellular carcinoma;
- With portal trunk or vena cava invasion;
- Having received interventional treatment such as TACE within 2 years
- Combined with medical contraindications that preclude any contrast-enhanced imaging (CT or MRI);
- Previous systemic therapy;
- Uncontrollable ascites, hepatic encephalopathy or bleeding esophagogastric fundic varices;
Show all 14Show fewer
- Hypertension that cannot be reduced to within normal limits with antihypertensive medication (systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg);
- Suffering from myocardial ischemia or myocardial infarction of grade II or higher, poorly controlled arrhythmia of grade II or higher myocardial ischemia or infarction, poorly controlled arrhythmia (QTc interval greater than or equal to 450 ms, QTc interval calculated in Fridericia metric).
- (calculated in Fridericia formula);
- History of gastrointestinal bleeding within the past 3 months or a clear tendency of gastrointestinal bleeding, such as: esophageal varices at risk of bleeding, locally active ulcer lesions, fecal occult blood (++);
- Pregnant or breastfeeding women; patients of childbearing potential who are unwilling or unable to use effective contraceptive measures
- HIV-infected patients;
- Those suspected of being allergic to the study drug;
- Other circumstances that, in the judgment of the investigator, may affect the conduct of the clinical study and the determination of the study results.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Guoliang Shao
Hangzhou, Zhejiang
Guoliang Shao, +8613958183472, shaoguoliang666@hotmail.com
About this study
The goal of this prospective, interventional clinical trial is to evaluation of fruquintinib in combination with sintulimab and TACE for inoperable primary hepatocellular carcinoma for progression-free survival (PFS).
Read the detailed description
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, accounting for approximately 745,000 deaths annually and 9.1% of all cancer-related deaths worldwide, with only about 30% of HCC patients having access to curative therapies. Most patients have intermediate to advanced disease and are usually treated with palliative therapy using TACE or systemic therapy (e.g., sorafenib, lenvatinib).
The efficacy of either sorafenib or lenvatinib as a single agent in the treatment of hepatocellular liver cancer remains limited, therefore, exploring combination therapy is one of the current research hotspots. A recent randomized, open, multicenter clinical study (TACTICS) enrolling patients with unresectable HCC showed that PFS was significantly prolonged to 25.2 months in the TACE combined with sorafenib treatment group, compared to 25.2 months in the TACE alone group. PFS was only 13.5 months in the TACE treatment group (HR=0. 59, 95%CI: 0.41-0. 87, P=0. 006). Median TTP was 24.1 months in the combination treatment group and 13.5 months in the TACE treatment group alone (HR=0. 56, 95%CL 0. 38-0. 83, P=0. 004).
Sintilimab, a recombinant fully human IgG4-type PD-1 monoclonal antibody, is an innovative drug developed by Sintilimab (Suzhou) Co. At the end of 2018, Sintilimab was officially approved by the NMPA of china for the treatment of relapsed or refractory classic Hodgkin's lymphoma (cHL) after at least second-line systemic chemotherapy. As a biosimilar to pembrolizumab, sintilimab has great potential to play a role similar to that played by pembrolizumab in primary hepatocellular carcinoma.
Fruquintinib is a potent small molecule VEGFR inhibitor developed by Hutchmed Ltd. with full intellectual property rights, with high kinase selectivity and inhibitory activity only for the VEGFR kinase family (VEGFR1, 2 and 3).On September 5, 2018, the NMPA of china officially approved fruquintinib for patients who have previously received fluorouracil-based, oxaliplatin and irinotecan-based chemotherapy, and for patients with metastatic colorectal cancer (mCRC) who have received prior or are not suitable for prior anti-vascular endothelial growth factor (VEGF) therapy, anti-epidermal growth factor receptor (EGFR) therapy (RAS wild type).
Therefore, based on previous studies, this study intended to select patients with unresectable primary hepatocellular carcinoma, and prospectively observe the efficacy and safety of fruquintinib in combination with sintilimab and TACE in the treatment of unresectable CNLC(China liver cancer staging) 2b-3a patients.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Fruquintinib, Sintilimab, Transcatheter arterial chemoembolization（TACE）
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FruquintinibDrug
Fruquintinib:5 mg capsule orally once daily on day 1-21 in 28-day cycles；
SintilimabDrug
Sintilimab: 200 mg i.v. every 3 weeks
Transcatheter arterial chemoembolization（TACE）Device
Transcatheter arterial chemoembolization（TACE）
| Study group | Role | What they receive |
|---|---|---|
| treatment | Experimental | Fruquintinib+sintilimab+TACE Receives: Drug: Fruquintinib; Drug: Sintilimab; Device: Transcatheter arterial chemoembolization（TACE） |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival(PFS)
Progression free survival period refers to the period from the beginning of treatment to the time when patients with cancer progress is observed or death occurs for any reason.
Measured: 1 year
Secondary outcomes (5)
Object response rate(ORR)
The proportion of patients whose tumor volume reduction reaches the predetermined value and can maintain the minimum time limit. It is the sum of the proportion of complete response (CR) and partial response(PR).
Measured: Change from baseline tumor volume at 6 months
Time to response(TTR)
Time to response
Measured: through study completion, an average of 1 year
Disease control rate(DCR)
It is the sum of the proportion of complete response (CR), partial response(PR) and stable disease(SD).
Measured: 1 year
Overall survival(OS)
(OS) is defined as the time from the patient's first dose of study drug until any cause of their death.
Measured: 1 year
Time to progression(TTP)
Time from the beginning of treatment to the objective progression of tumor
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2023
- Study start23 Nov 2021
- Primary completion23 Dec 2024 (estimated)
- Study completion23 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Zhejiang Cancer HospitalThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- fruquintinib+sintilimab+TACE
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guoliang Shao, Zhejiang Cancer Hospital
- Investigators
- Guoliang Shao, Principal investigator, Zhejiang Cancer Hospital Hangzhou, Zhejiang, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05971199
- Sponsor's protocol ID
- IRB-2021-385
- Status last verified
- Aug 2023
- First submitted
- 10 Jul 2023
- Last updated
- 2 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Fruquintinib Combined With Sintilimab and TACE for Inoperable Primary Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05971199
- Acronym / sponsor ID
- IRB-2021-385
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Zhejiang Cancer HospitalUniversity, hospital or other
- Study start
- 23 Nov 2021 (actual)
- Primary completion
- 23 Dec 2024 (estimated)
- Study completion
- 23 Dec 2024 (estimated)
- First posted
- 2 Aug 2023 (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.
The goal of this prospective, interventional clinical trial is to evaluation of fruquintinib in combination with sintulimab and TACE for inoperable primary hepatocellular carcinoma for progression-free survival (PFS).
Detailed description
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, accounting for approximately 745,000 deaths annually and 9.1% of all cancer-related deaths worldwide, with only about 30% of HCC patients having access to curative therapies. Most patients have intermediate to advanced disease and are usually treated with palliative therapy using TACE or systemic therapy (e.g., sorafenib, lenvatinib).
The efficacy of either sorafenib or lenvatinib as a single agent in the treatment of hepatocellular liver cancer remains limited, therefore, exploring combination therapy is one of the current research hotspots. A recent randomized, open, multicenter clinical study (TACTICS) enrolling patients with unresectable HCC showed that PFS was significantly prolonged to 25.2 months in the TACE combined with sorafenib treatment group, compared to 25.2 months in the TACE alone group. PFS was only 13.5 months in the TACE treatment group (HR=0. 59, 95%CI: 0.41-0. 87, P=0. 006). Median TTP was 24.1 months in the combination treatment group and 13.5 months in the TACE treatment group alone (HR=0. 56, 95%CL 0. 38-0. 83, P=0. 004).
Sintilimab, a recombinant fully human IgG4-type PD-1 monoclonal antibody, is an innovative drug developed by Sintilimab (Suzhou) Co. At the end of 2018, Sintilimab was officially approved by the NMPA of china for the treatment of relapsed or refractory classic Hodgkin's lymphoma (cHL) after at least second-line systemic chemotherapy. As a biosimilar to pembrolizumab, sintilimab has great potential to play a role similar to that played by pembrolizumab in primary hepatocellular carcinoma.
Fruquintinib is a potent small molecule VEGFR inhibitor developed by Hutchmed Ltd. with full intellectual property rights, with high kinase selectivity and inhibitory activity only for the VEGFR kinase family (VEGFR1, 2 and 3).On September 5, 2018, the NMPA of china officially approved fruquintinib for patients who have previously received fluorouracil-based, oxaliplatin and irinotecan-based chemotherapy, and for patients with metastatic colorectal cancer (mCRC) who have received prior or are not suitable for prior anti-vascular endothelial growth factor (VEGF) therapy, anti-epidermal growth factor receptor (EGFR) therapy (RAS wild type).
Therefore, based on previous studies, this study intended to select patients with unresectable primary hepatocellular carcinoma, and prospectively observe the efficacy and safety of fruquintinib in combination with sintilimab and TACE in the treatment of unresectable CNLC(China liver cancer staging) 2b-3a patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- fruquintinib+sintilimab+TACE
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Drug: Fruquintinib, Drug: Sintilimab, Device: Transcatheter arterial chemoembolization（TACE）Fruquintinib+sintilimab+TACE |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 18-75 years, male or female;
- Patients diagnosed with primary hepatocellular carcinoma (HCC) based on clinical diagnosis or pathology;
- Patients diagnosed with Chinese stage IIb-IIIa according to the Primary Liver Cancer Diagnostic and Treatment Protocol (2019 version), and evaluated by the investigator to be unable to undergo surgical treatment, such as resection, ablation or liver transplantation;
- Imaging reports within 14 days prior to the intervention showed the presence of at least 1 target lesion measurable by CT or MRI, and the lesion is suitable for repeated accurate measurements;
- Child-Pugh liver function rating: grade A or better B (≤7 points);
Key exclusion criteria (14 listed)
- Hepatobiliary cell carcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma and fibrous lamellar hepatocellular carcinoma;
- With portal trunk or vena cava invasion;
- Having received interventional treatment such as TACE within 2 years
- Combined with medical contraindications that preclude any contrast-enhanced imaging (CT or MRI);
- Previous systemic therapy;
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 |
|---|---|---|
| FruquintinibFruquintinib:5 mg capsule orally once daily on day 1-21 in 28-day cycles； | Drug | treatment |
| SintilimabSintilimab: 200 mg i.v. every 3 weeks | Drug | treatment |
| Transcatheter arterial chemoembolization（TACE）Transcatheter arterial chemoembolization（TACE） | Device | treatment |
Primary outcome
Progression-free survival(PFS)
Time frame: 1 year
Progression free survival period refers to the period from the beginning of treatment to the time when patients with cancer progress is observed or death occurs for any reason.
5 secondary outcomes
Object response rate(ORR)
Time frame: Change from baseline tumor volume at 6 months
Time to response(TTR)
Time frame: through study completion, an average of 1 year
Disease control rate(DCR)
Time frame: 1 year
Overall survival(OS)
Time frame: 1 year
Time to progression(TTP)
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2023.
Related trials for Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
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.
Guoliang Shao principal investigator
Zhejiang Cancer Hospital Hangzhou, Zhejiang, China
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 Fruquintinib, Sintilimab and Transcatheter arterial chemoembolization（TACE） in people with Hepatocellular Carcinoma, run by Zhejiang Cancer Hospital 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 10 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 2 Aug 2023. 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 Guoliang Shao (+8613958183472, shaoguoliang666@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival(PFS) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Aug 2023.