Hepato Cellular Carcinoma (HCC)Phase 2NCT06812039
HAIC Combined with Donafenib and Sintilimab As Perioperative Treatment for Resectable Hepatocellular Carcinoma Patients At High Risk of Recurrence
A Phase 2 study testing HAIC combined with sintilimab and donafenib, Sintilimab and Donafenib and Surgery in people with Hepato Cellular Carcinoma (HCC), run by Fudan University at 3 sites in China.
Trial summary
This study will evaluate the efficacy and safety of therapy perioperative treatment with HAIC combined with donafenib and sintilimab (group A)/ donafenib combined with sintilimab (group B) compared with direct surgery (group C) in resectable HCC patients who are at high risk for disease recurrence. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepato Cellular Carcinoma (HCC)
- What is being tested?
- HAIC combined with sintilimab and donafenib, Sintilimab and Donafenib and Surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- 3 sitesChina
- Study dates
- 1 Jan 2025to 31 Jan 2028
- Phase
- Phase 2
- 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
- Voluntary enrollment with written informed consent obtained
- Age 18 to 75 years (inclusive), regardless of gender
- Histologically or pathologically confirmed previously untreated hepatocellular carcinoma (HCC) or clinically diagnosed previously untreated HCC according to the AASLD guidelines.
- Initial resectable status as assessed by the investigator (expected to achieve R0 resection, sufficient liver remnant volume, and Child-Pugh class A, as per the "Chinese Expert Consensus on Neoadjuvant Therapy for Liver Cancer (2023 Edition)").
- At least one measurable lesion according to mRECIST criteria.
- Tumor burden meets one of the following conditions:
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- A single tumor with a diameter > 5 cm;
- Multiple tumors with the largest tumor diameter > 3 cm, with < 5 tumors in total;
- Presence of portal vein tumor thrombus (Vp1-Vp2).
- Liver function: Child-Pugh score of 5-6.
- ECOG 0-1
- Life expectancy of at least 3 months.
- Women of childbearing potential (defined as not postmenopausal or surgically sterilized) must have a negative serum pregnancy test within 7 days prior to the study drug administration.
- Both women and men of childbearing potential must use reliable contraception during the study and for 60 days following the last dose of the study drug.
- For HBV-infected patients: If HBV-DNA is ≥ 10⁴ copies/ml within 14 days prior to enrollment, antiviral therapy (preferably entecavir) must be initiated to reduce HBV-DNA to < 10⁴ copies/ml before entering the study. Antiviral therapy should continue, with regular monitoring of liver function and HBV-DNA levels.
- Adequate organ function.
Who cannot join
- Patients with distant metastasis.
- Patients with portal vein tumor thrombosis (Vp3-Vp4).
- History of any other malignant tumor within the past 5 years, unless the patient has received potentially curative treatment and there is no evidence of recurrence in the past 5 years. This 5-year time requirement does not apply to patients who have successfully undergone resection for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ.
- History or current presence of congenital or acquired immunodeficiency diseases.
- Active or previously documented autoimmune diseases or inflammatory disorders (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, pituitary inflammation, hyperthyroidism or hypothyroidism, asthma requiring bronchodilators for treatment, etc.). Patients with vitiligo or asthma fully resolved in childhood and not requiring intervention as adults may be included.
- History of severe psychiatric disorders.
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- Conditions affecting the absorption, distribution, metabolism, or elimination of the study drugs (e.g., severe vomiting, chronic diarrhea, bowel obstruction, malabsorption, etc.).
- Major surgery within 4 weeks prior to enrollment (as defined by the investigator).
- History of allogeneic stem cell or solid organ transplantation (except for corneal transplantation).
- Received other systemic antitumor therapies (including traditional Chinese medicine with antitumor indications) within 2 weeks or 5 half-lives (whichever is longer) prior to study drug administration, or unresolved adverse events related to prior treatments that have not recovered to ≤ CTCAE Grade 1.
- Use of systemic immunosuppressive drugs within 2 weeks prior to enrollment, or anticipated need for systemic immunosuppressive therapy during the study.
- Concurrent use of drugs that may prolong the QTc interval and/or induce Tdp, or drugs affecting drug metabolism.
- Known or suspected allergy to donafenib, recombinant humanized PD-1 monoclonal antibodies, or similar agents, or a history of hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or to excipients of the study drugs.
- Uncontrolled hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion, or pericardial effusion.
- Active bleeding or coagulation disorders, bleeding tendencies, or ongoing treatment with thrombolytics, anticoagulants, or antiplatelet therapy.
- History of gastrointestinal bleeding or clear gastrointestinal bleeding tendencies within the past 6 months (e.g., known active ulcerative lesions, positive stool occult blood with ≥2+ results, requiring endoscopy if stool occult blood remains positive), or other conditions that may lead to gastrointestinal bleeding as determined by the investigator (e.g., severe esophageal/gastric varices).
- History of gastrointestinal perforation, abdominal fistulas, or intra-abdominal abscesses within the past 6 months.
- History of thrombosis or thromboembolic events (e.g., stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the past 6 months.
- Significant cardiovascular disease, including but not limited to: acute myocardial infarction, severe/uncontrolled angina, coronary artery bypass grafting within the past 6 months; congestive heart failure (NYHA class >2); poorly controlled arrhythmias requiring pacemaker treatment; drug-resistant hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg).
- Active infection.
- Other significant clinical or laboratory abnormalities that may affect safety evaluation, such as uncontrolled diabetes, chronic kidney disease, grade 2 or higher peripheral neuropathy (CTCAE v5.0), thyroid dysfunction, etc.
- Use of live attenuated vaccines within 4 weeks prior to enrollment or during the study.
- Pregnant or breastfeeding women, or women or men of childbearing potential unwilling or unable to use effective contraception.
- History of alcohol, drug, or substance abuse within the past 6 months.
- Participation in any other clinical trial involving investigational drugs or medical devices within 4 weeks prior to enrollment.
- Inability to comply with the study protocol for treatment or follow-up visits.
- Any other conditions that, in the opinion of the investigator, would preclude participation in the study.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Not yet recruiting
Fujian Cancer Hospital
Fuzhou, Fujian, 350014
Hui Zhang, 18017317636, sysucczyf@163.com
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200062
Lu Wang, M.D., +86-18121299357, w.lr@hotmail.com
- Not yet recruiting
TianJin Medical University Cancer Institute & Hospital
Tianjin, Tianjin Municipality, 300000
Huikai Li, M.D., 18017317636, sysucczyf@163.com
About this study
Official title: HAIC Combined with Donafenib and Sintilimab As Perioperative Treatment for Resectable Hepatocellular Carcinoma Patients At High Risk of Recurrence: a Prospective, Multicenter, Randomized Phase II Study
This study will evaluate the efficacy and safety of therapy perioperative treatment with HAIC combined with donafenib and sintilimab (group A)/ donafenib combined with sintilimab (group B) compared with direct surgery (group C) in resectable HCC patients who are at high risk for disease recurrence.
- Conditions
- Hepato Cellular Carcinoma (HCC)
- Being tested
- HAIC combined with sintilimab and donafenib, Sintilimab and Donafenib, Surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HAIC combined with sintilimab and donafenibDrug
HAIC: Two cycles, Q3W. The chemotherapy regimen consists of oxaliplatin 85 mg/m² over 2 hours and raltitrexed 2 mg/m² over 1 hour.
Donafenib: Treatment should begin the day after the completion of the first HAIC, with an initial dose of 0.1g bid p.o.. The investigator may increase the dose to 0.2g bid depending on the patient's condition.
Sintilimab: Administration may begin after the first HAIC, 200 mg iv Q3W. After surgery, continued sintilimab and donafenib for 6 cycles.
Sintilimab and DonafenibDrug
Donafenib: an initial dose of 0.1g bid p.o. The investigator may increase the dose to 0.2g bid depending on the patient's condition. Sintilimab: 200 mg iv Q3W. After surgery, continued sintilimab and donafenib for 6 cycles.
SurgeryProcedure or surgery
After surgery, received sintilimab and donafenib for 6 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | HAIC combined with sintilimab and donafenib Receives: Drug: HAIC combined with sintilimab and donafenib |
| Group B | Experimental | Sintilimab and Donafenib Receives: Drug: Sintilimab and Donafenib |
| Group C | Active comparator | Direct surgery Receives: Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-yr RFS rate
the proportion of patients who have not experienced recurrence or death from any cause at 12 months after hepatectomy.
Measured: 24 months
Secondary outcomes (7)
MPR rate
The percentage of patients with 70%-99% tumor necrosis found during surgery after neoadjuvant therapy
Measured: Up to approximately 12 weeks
pCR rate
the percentage of participants having a pathCR
Measured: Up to approximately 12 weeks
ORR
The percentage of subjects in the overall population who achieved CR or PR according to the mRECIST criteria
Measured: Up to approximately 12 weeks
RFS
RFS is defined as the time from liver resection to the first documented occurrence of intrahepatic or extrahepatic HCC, or death from any cause (whichever occurs first).
Measured: Up to approximately 2 years
PFS
PFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC, or death from any cause (whichever occurs first).
Measured: Up to approximately 2 years
OS
OS is defined as the time from randomization to death from any cause.
Measured: Up to approximately 3 years
TTR
TTR is defined as the time from liver resection to the first documented occurrence of intrahepatic or extrahepatic HCC.
Measured: Up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2025
- Study start1 Jan 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepato Cellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Fudan 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 165 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lu Wang, MD, PhD, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06812039
- Sponsor's protocol ID
- 2412311-5
- Status last verified
- Feb 2025
- First submitted
- 19 Jan 2025
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HAIC Combined with Donafenib and Sintilimab As Perioperative Treatment for Resectable Hepatocellular Carcinoma Patients At High Risk of Recurrence: a Prospective, Multicenter, Randomized Phase II Study
- ClinicalTrials.gov ID
- NCT06812039
- Acronym / sponsor ID
- 2412311-5
- Conditions
- Hepato Cellular Carcinoma (HCC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 165 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Jan 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Jan 2028 (estimated)
- First posted
- 6 Feb 2025 (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.
This study will evaluate the efficacy and safety of therapy perioperative treatment with HAIC combined with donafenib and sintilimab (group A)/ donafenib combined with sintilimab (group B) compared with direct surgery (group C) in resectable HCC patients who are at high risk for disease recurrence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: HAIC combined with sintilimab and donafenibHAIC combined with sintilimab and donafenib |
| Group B | Experimental | Drug: Sintilimab and DonafenibSintilimab and Donafenib |
| Group C | Active comparator | Procedure: SurgeryDirect surgery |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Voluntary enrollment with written informed consent obtained
- Age 18 to 75 years (inclusive), regardless of gender
- Histologically or pathologically confirmed previously untreated hepatocellular carcinoma (HCC) or clinically diagnosed previously untreated HCC according to the AASLD guidelines.
- Initial resectable status as assessed by the investigator (expected to achieve R0 resection, sufficient liver remnant volume, and Child-Pugh class A, as per the "Chinese Expert Consensus on Neoadjuvant Therapy for Liver Cancer (2023 Edition)").
- At least one measurable lesion according to mRECIST criteria.
Key exclusion criteria (27 listed)
- Patients with distant metastasis.
- Patients with portal vein tumor thrombosis (Vp3-Vp4).
- History of any other malignant tumor within the past 5 years, unless the patient has received potentially curative treatment and there is no evidence of recurrence in the past 5 years. This 5-year time requirement does not apply to patients who have successfully undergone resection for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ.
- History or current presence of congenital or acquired immunodeficiency diseases.
- Active or previously documented autoimmune diseases or inflammatory disorders (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, pituitary inflammation, hyperthyroidism or hypothyroidism, asthma requiring bronchodilators for treatment, etc.). Patients with vitiligo or asthma fully resolved in childhood and not requiring intervention as adults may be included.
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 |
|---|---|---|
| HAIC combined with sintilimab and donafenibHAIC: Two cycles, Q3W. The chemotherapy regimen consists of oxaliplatin 85 mg/m² over 2 hours and raltitrexed 2 mg/m² over 1 hour. Donafenib: Treatment should begin the day after the completion of the first HAIC, with an initial dose of 0.1g bid p.o.. The investigator may increase the dose to 0.2g bid depending on the patient's condition. Sintilimab: Administration may begin after the first HAIC, 200 mg iv Q3W. After surgery, continued sintilimab and donafenib for 6 cycles. | Drug | Group A |
| Sintilimab and DonafenibDonafenib: an initial dose of 0.1g bid p.o. The investigator may increase the dose to 0.2g bid depending on the patient's condition. Sintilimab: 200 mg iv Q3W. After surgery, continued sintilimab and donafenib for 6 cycles. | Drug | Group B |
| SurgeryAfter surgery, received sintilimab and donafenib for 6 cycles. | Procedure or surgery | Group C |
Primary outcome
1-yr RFS rate
Time frame: 24 months
the proportion of patients who have not experienced recurrence or death from any cause at 12 months after hepatectomy.
7 secondary outcomes
MPR rate
Time frame: Up to approximately 12 weeks
pCR rate
Time frame: Up to approximately 12 weeks
ORR
Time frame: Up to approximately 12 weeks
RFS
Time frame: Up to approximately 2 years
PFS
Time frame: Up to approximately 2 years
OS
Time frame: Up to approximately 3 years
TTR
Time frame: Up to approximately 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- 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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HAIC combined with sintilimab and donafenib, Sintilimab and Donafenib and Surgery in people with Hepato Cellular Carcinoma (HCC), run by Fudan University at 3 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 16 inclusion and 27 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 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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.
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?
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 Lu Wang, M.D. (86-18121299357, w.lr@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-yr RFS rate (time frame: 24 months). 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 6 Feb 2025.