Hepatocellular CarcinomaPhase 1CISLD-8NCT04418401
Study on the Safety and Efficacy of Donafinib Combined With Anti-PD-1 Antibody as Adjuvant Therapy for HCC Patients
A Phase 1 study testing Donafenib and anti-PD-1 antibody in people with Hepatocellular Carcinoma, run by Zhejiang University at 1 site in China.
Trial summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with more than 700,000 new cases in the world every year. China has the highest incidence and death rate of HCC in the world, accounting for 55% of the world's annual incidence and 45% of the world's annual deaths. 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?
- Donafenib and anti-PD-1 antibody
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 11 Jun 2020to 1 Nov 2025
- Phase
- Phase 1
- 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
- 1)Voluntary admission and signature of written informed consent;
- 2)18~75 years of age (including 75 years), male and female;
- 3)Hepatocellular carcinoma underwent radical resection 4~8 weeks before enrolled.
- 4)Pathologically diagnosed as hepatocellular carcinoma with any of the following conditions: a)Microvascular invasion (MVI); b)Satellite nodules were found in specimens; c)Multiple tumor nodules(>3 nodules); d)Portal vein tumor thrombosis (PVTT): The tumor thrombosis invades the left or right branches of portal vein, with or without hepatic vein invasion;
- 5)≥4 weeks after radical resection, the imaging examination confirmed no recurrence and metastasis.
- 6)Liver function Child-Pugh grade A (5~6);
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- 7)Physical condition was scored 0~1 according to the ECOG criteria.
- 8)Expected lifetime >3 months;
- 9)HBV DNA<10^4 copy/ ml (2000 IU/ ml); if HBV DNA ≥10^4 copy/ ml, antiviral therapy should be given, until the HBV DNA drops below 10^4Copy/ml patient can be enrolled in the study. And during the study, antiviral drugs should be continued, and liver function and hepatitis B virus load should be monitored;
- 10)The results of the serum pregnancy test must be negative for women with fertility (i.e. non-menopausal or surgical sterilization) within 7 days prior to the study of drug administration;
- 11)The main organs function normally: Blood routine examination (no transfusion, no use of G-CSF within 14 days before screening): a)Hemoglobin ≥90 g/L; b)Absolute neutrophil count (ANC)≥1.5×10^9/L; c)Platelet count ≥75×10^9/L; Blood biochemical examination (albumin not used within 14 days before screening): d)Albumin ≥28 g/L; e)Total bilirubin ≤1.5× ULN; f)Aspartate aminotransferase (AST), alanine aminotransferase (ALT )≤3× ULN; g)Serum creatinine ≤1.5×ULN; Coagulation function: h)The international standardized ratio (INR) or prothrombin time (PT )≤1.5×ULN;. i)Activated partial thromboplastin time (APTT )≤1.5×ULN.
Who cannot join
- Histopathological diagnosis of hepatocellular carcinoma - intrahepatic cholangiocarcinoma (HCC-ICC) mixed type;
- Positive resection margin or tumor rupture;
- Operation of recurrent liver cancer;
- Other malignancies within 5 years unless the patient has received a possible cure and there is no evidence of the disease within 5 years, but this time requirement (i.e. within 5 years) is not applicable to patients with skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or other carcinoma in situ who have successfully undergone excision;
- Previous or present congenital or acquired immunodeficiency disease;
- Active or previously documented autoimmune or inflammatory diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, pituitary inflammation, hyperthyroidism or hypothyroidism, asthma requiring treatment with bronchiectasis, etc.), asthma with vitiligo or which has been completely relieved in childhood without inclusion of any intervention in adults;
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- History of severe mental illness;
- Suffer from diseases (e.g. severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.) that affect the absorption, distribution, metabolism or clearance of the study drug;
- Past or combined medication/treatment:
- Had major surgery (defined by the investigators) within 4 weeks before admission, or expected to require major surgery during study therapy;
- Previous transplantation of allogeneic stem cells or parenchymal organs;
- Preoperative treatment with sorafenib, valvatinib, regofenib or immunomodulator such as anti PD-1、 PD-L1、 anti CTLA-4;
- Patients who have received other systemic anti-tumor treatments before surgery, including traditional Chinese medicine with anti-tumor indications, have had less than 2 weeks or 5 half-time (whichever is longer) between the completion of the treatment and the use of the drugs before the study, or who have not recovered to ≤CTCAE 1 level of adverse events caused by preoperative treatment;
- Other adjuvant therapy (except antiviral therapy) was performed after operation.
- Systemic immunosuppressive drugs have been used within 2 weeks before admission or are expected to be required during the study period, except in the following cases: a)Intra-nasal, inhalation, topical or topical (e.g. intra-articular) corticosteroids; b)Prednisone ≤ 10 mg/day or other equivalent systemic corticosteroid; c)Prophylactic use of corticosteroids for hypersensitivity;
- Take drugs that may prolong QTc and/or induce advanced torsional ventricular tachycardia (Tdp) or affect drug metabolism;
- Patients with known or suspected history of allergies to Donafenib or similar drugs, hypersensitivity to chimeric or humanized antibodies or fusion proteins, or to excipients used to study drugs;
- The presence of uncontrollable hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion;
- Active bleeding or abnormal coagulation function, bleeding tendency or undergoing thrombolytic, anticoagulant or antiplatelet therapy;
- There was a history of gastrointestinal bleeding or a definite tendency of gastrointestinal bleeding in the past 4 weeks (e.g. local active ulcer lesions, stool occult blood≥ ++ , e.g. continuous stool occult blood +, gastroscopy should be performed), or other conditions (e.g. severe gastric fundus/esophageal varices) that the researchers determined might cause gastrointestinal bleeding;
- Gastrointestinal perforation, abdominal fistula or abdominal abscess occurred within 6 months.
- Thrombosis or thromboembolic events, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc., occurred within 6 months.
- With significant clinical significance, including but not limited to previous 6 months of acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting, congestive heart failure (New York Heart Association NYHA Grade > Grade 2), Poor control or arrhythmia requiring pacemaker therapy, Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg);
- Active infections, including: a)HIV (HIV 1/2 antibody) positive; b)Active hepatitis B (HBsAg positive and abnormal liver function); c)Active hepatitis C (HCV antibody positive or HCV RNA≥10^3 copy/ ml and abnormal liver function); d)Active tuberculosis; e)Other uncontrolled active infections (CTCAE V5.0> level 2);
- Other significant clinical and laboratory abnormalities, the researchers believe affect safety evaluation, such as: uncontrolled diabetes, chronic kidney disease, peripheral neuropathy (CTCAE V5.0) of grade II or above, thyroid dysfunction, etc.
- Has not recovered from surgery, such as the presence of unhealed incisions or severe postoperative complications;
- Received any live attenuated vaccine within 4 weeks of admission or during the study period;
- Pregnant or lactating women, as well as women or men with fertility who are unwilling or unable to take effective contraception;
- A history of alcohol, psychotropic or other substance abuse within 6 months;
- Enrolled in other clinical trials within 4 weeks before admission.
- Failure to follow the study protocol for treatment or scheduled follow-up;
- Any other factors evaluated by investigators that patients cannot be enrolled.
Trial locations and contacts
1 site in 1 country.
China1 site
the First Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310003
About this study
Official title: A Study on the Safety and Efficacy of Donafinib Combined With Anti-PD-1 Antibody as Adjuvant Therapy for HCC Patients With High Risks of Recurrence
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with more than 700,000 new cases in the world every year. China has the highest incidence and death rate of HCC in the world, accounting for 55% of the world's annual incidence and 45% of the world's annual deaths. At present, surgical resection is still one of the most effective treatments for HCC. However, the recurrence rate of tumor after hepatectomy is still very high, and the recurrence rate of 5 years is 60~70%. Especially in patients with high-risk recurrence factors, without intervention, the cumulative recurrence rate in the first year was about 50%, about 60% in the second year, about 70% in the third year, and about 80% in the fifth year. Tumor recurrence is an important bottleneck that hinders the long-term survival of patients. Therefore, there is an urgent need for effective adjuvant therapy to reduce the postoperative recurrence rate of patients with HCC, especially high-risk patients. However, there is still a lack of standard protocols for postoperative adjuvant therapy for HCC. Here investigators intend to explore the safety and efficacy of Donafinib Combined With Anti-PD-1 Antibody as postoperative adjuvant therapy for HCC patients with high risks of recurrence.
Read the detailed description
This is a single center, open, single arm, and exploratory study. Thirty HCC patients with high risk recurrence factors after radical surgery will be enrolled. Adjuvant treatment of Donafenib combined with anti-PD-1 antibody will be given for 6 months. The primary endpoint is the cumulative percentage of patients without recurrence in the first year. The recurrence-free survival (RFS), overall survival (OS), tumor recurrence time (TTR), ECOG physical condition (ECOG PS) score, the changes of FACT-Hep based quality of life score, changes of AFP, and adverse events will be recorded and analyzed, to evaluated the efficacy and safety of this combination treatment.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Donafenib and anti-PD-1 antibody
- Keywords
- Hepatocellular Carcinoma, Postoperation, High risk of recurrence
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donafenib and anti-PD-1 antibodyDrug
Donafenib was taken orally twice daily, and anti-PD-1 antibody was applied biweekly.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Treatment with Donafenib 100mg PO BID，and anti-PD-1 antibody 3mg/kg ivgtt Q2W. Treatment will last 6 months, unless the tumor recurrence. Receives: Drug: Donafenib and anti-PD-1 antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free rate in one year
The cumulative percentage of patients without recurrence in the first year after the primary surgery
Measured: Through the study period, for 3 years
Secondary outcomes (6)
Recurrence-free survival
The period from the first study treatment to disease recurrence
Measured: Through the study period, for 3 years
Overall survival
The period from the first study treatment to any cause of death
Measured: Through the study period, for 3 years
ECOG physical condition 8/5000 ECOG physical condition
The changes of physical condition evaluated according to the criteria of Eastern Cooperative Oncology Group
Measured: Through the study period, for 3 years
FACT-Hep QLQ
The change of the quality of life
Measured: Through the study period, for 3 years
Alpha fetoprotein
The change of AFP
Measured: Through the study period, for 3 years
Adverse effects
Adverse events occurring through the study treatment, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.
Measured: Through the study period, for 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2020
- Study start11 Jun 2020
- Primary completion1 Nov 2025
- Study completion1 Nov 2025
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 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 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, TingBo Liang, Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04418401
- Sponsor's protocol ID
- CISLD-8
- Acronym
- CISLD-8
- Status last verified
- Nov 2025
- First submitted
- 3 Jun 2020
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study on the Safety and Efficacy of Donafinib Combined With Anti-PD-1 Antibody as Adjuvant Therapy for HCC Patients With High Risks of Recurrence
- ClinicalTrials.gov ID
- NCT04418401
- Acronym / sponsor ID
- CISLD-8 / CISLD-8
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma, Postoperation, High risk of recurrence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Zhejiang UniversityUniversity, hospital or other
- Study start
- 11 Jun 2020 (actual)
- Primary completion
- 1 Nov 2025 (actual)
- Study completion
- 1 Nov 2025 (actual)
- First posted
- 5 Jun 2020 (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.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with more than 700,000 new cases in the world every year. China has the highest incidence and death rate of HCC in the world, accounting for 55% of the world's annual incidence and 45% of the world's annual deaths. At present, surgical resection is still one of the most effective treatments for HCC. However, the recurrence rate of tumor after hepatectomy is still very high, and the recurrence rate of 5 years is 60~70%. Especially in patients with high-risk recurrence factors, without intervention, the cumulative recurrence rate in the first year was about 50%, about 60% in the second year, about 70% in the third year, and about 80% in the fifth year. Tumor recurrence is an important bottleneck that hinders the long-term survival of patients. Therefore, there is an urgent need for effective adjuvant therapy to reduce the postoperative recurrence rate of patients with HCC, especially high-risk patients. However, there is still a lack of standard protocols for postoperative adjuvant therapy for HCC. Here investigators intend to explore the safety and efficacy of Donafinib Combined With Anti-PD-1 Antibody as postoperative adjuvant therapy for HCC patients with high risks of recurrence.
Detailed description
This is a single center, open, single arm, and exploratory study. Thirty HCC patients with high risk recurrence factors after radical surgery will be enrolled. Adjuvant treatment of Donafenib combined with anti-PD-1 antibody will be given for 6 months. The primary endpoint is the cumulative percentage of patients without recurrence in the first year. The recurrence-free survival (RFS), overall survival (OS), tumor recurrence time (TTR), ECOG physical condition (ECOG PS) score, the changes of FACT-Hep based quality of life score, changes of AFP, and adverse events will be recorded and analyzed, to evaluated the efficacy and safety of this combination treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: Donafenib and anti-PD-1 antibodyTreatment with Donafenib 100mg PO BID，and anti-PD-1 antibody 3mg/kg ivgtt Q2W. Treatment will last 6 months, unless the tumor recurrence. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1)Voluntary admission and signature of written informed consent;
- 2)18~75 years of age (including 75 years), male and female;
- 3)Hepatocellular carcinoma underwent radical resection 4~8 weeks before enrolled.
- 4)Pathologically diagnosed as hepatocellular carcinoma with any of the following conditions: a)Microvascular invasion (MVI); b)Satellite nodules were found in specimens; c)Multiple tumor nodules(>3 nodules); d)Portal vein tumor thrombosis (PVTT): The tumor thrombosis invades the left or right branches of portal vein, with or without hepatic vein invasion;
- 5)≥4 weeks after radical resection, the imaging examination confirmed no recurrence and metastasis.
Key exclusion criteria (32 listed)
- Histopathological diagnosis of hepatocellular carcinoma - intrahepatic cholangiocarcinoma (HCC-ICC) mixed type;
- Positive resection margin or tumor rupture;
- Operation of recurrent liver cancer;
- Other malignancies within 5 years unless the patient has received a possible cure and there is no evidence of the disease within 5 years, but this time requirement (i.e. within 5 years) is not applicable to patients with skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or other carcinoma in situ who have successfully undergone excision;
- Previous or present congenital or acquired immunodeficiency disease;
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 |
|---|---|---|
| Donafenib and anti-PD-1 antibodyDonafenib was taken orally twice daily, and anti-PD-1 antibody was applied biweekly. | Drug | Experimental group |
Primary outcome
Recurrence-free rate in one year
Time frame: Through the study period, for 3 years
The cumulative percentage of patients without recurrence in the first year after the primary surgery
6 secondary outcomes
Recurrence-free survival
Time frame: Through the study period, for 3 years
Overall survival
Time frame: Through the study period, for 3 years
ECOG physical condition 8/5000 ECOG physical condition
Time frame: Through the study period, for 3 years
FACT-Hep QLQ
Time frame: Through the study period, for 3 years
Alpha fetoprotein
Time frame: Through the study period, for 3 years
Adverse effects
Time frame: Through the study period, for 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Donafenib and anti-PD-1 antibody in people with Hepatocellular Carcinoma, run by Zhejiang 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 11 inclusion and 32 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: finished, as of the sponsor's last update on 17 Feb 2026. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence-free rate in one year (time frame: Through the study period, for 3 years). 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 17 Feb 2026.