Hepatocellular Carcinoma with PVTTPhase 2DoTHNCT06646198
TIPS Plus Half-dose Donafenib in AHCC with PVTT-associated Portal Hypertension
A Phase 2 study testing Transjugular intrahepatic portosystemic shunt (TIPS) and Donafenib in people with Hepatocellular Carcinoma with PVTT, run by Fei Gao at 1 site in China.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) plus half-dose donafenib (a kind of anti-angiogenesis agents) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma with PVTT
- What is being tested?
- Transjugular intrahepatic portosystemic shunt (TIPS) and Donafenib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 8 Oct 2024to 31 Dec 2026
- 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
- The patient voluntarily joined the study and signed an informed consent form;
- ≥18 and ≤ 75 years old, both male and female;
- Pathologically confirmed hepatocellular carcinoma, at least one measurable focus without local treatment (according to mRECIST or RECIST 1.1 requirements;
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
- BCLC-C stage accompanied by tumor thrombosis-associated portal hypertension;
- Newly diagnosed patients who have not received local or systemic therapy in the past;
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- Expected survival period ≥ 3 months;
- The functions of vital organs meet the following requirements (no blood components, cell growth factors and other corrective treatment drugs are allowed within 14 days before the first administration): the absolute count of neutrophils≥1.5×10^9/L; Platelet ≥50×10^9/L; Hemoglobin ≥60 g/L; Serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH)≤1×ULN (if abnormal, the levels of FT3 and FT4 should be examined at the same time, if the levels of FT3 and FT4 are normal, they can be included in the group); Bilirubin≤2×ULN (within 7 days before the first administration); ALT and AST ≤5×ULN (within 7 days before the first dose); Serum creatinine≤1.5×ULN;
- Child-Pugh score ≤ 13 points;
- Diagnosed with portal hypertension-related complications: Gastrointestinal bleeding; refractory or recurrent ascites; hepatic pleural effusion; portal vein tumor thrombus exceeds 50% of lumen area.
- Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as an intrauterine device, contraceptive, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo surgical sterilization must be negative in serum or urine HCG within 72 hours before enrollment in the study; and must be non-lactating; for male patients whose partners are women of childbearing age, at the last time use effective methods for contraception within 3 months.
Who cannot join
- The patient has any active autoimmune disease or a history of autoimmune disease;
- The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment;
- Severe allergic reaction to any compositions of donafenib tablets or contrast media containing iodine ;
- Central nervous system metastasis;
- Patients who have received liver transplantation in the past;
- Tumor thrombus beyond the portal vein range, such as hepatic vein, inferior vena cava, right atrium, splenic vein, superior mesenteric vein;
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- Suffer from high blood pressure and cannot be well controlled by anti-hypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
- Uncontrolled cardiac clinical symptoms or diseases, such as: NYHA level 2 or higher heart failure, unstable angina pectoris, myocardial infarction occurred within 1 year, clinically significant supraventricular or ventricular arrhythmia requires treatment or intervention , QTc>450ms (male); QTc>470ms (female); Abnormal coagulation function (INR>2.0, PT>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow the preventive use of low-dose aspirin and low molecular heparin;
- Child-Pugh score >13 points;
- Arterial/venous thrombosis events that occurred within 6 months before randomization, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
- Known genetic or acquired bleeding and thrombotic tendency (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.);
- Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content> 1.0 g;
- The patient has active infection, fever of unknown origin within 7 days before medication ≥38.5℃, or baseline white blood cell count >15×109/L;
- Patients with congenital or acquired immune deficiencies (such as HIV-infected persons);
- Moderate to severe pulmonary hypertension, pulmonary artery pressure was assessed by ultrasound >40mmHg；
- The patient suffered from other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
- The patient has previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or has previously received apatinib therapy;
- According to the judgment of the investigator, the patient has other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illness) that require combined treatment, and other abnormalities which may affect the efficacy and/or safety of patients.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University
Guangzhou, Guangdong, 510060
Fei Gao, M.D.，Ph.D., +86-13760869828, gaof@sysucc.org.cn
Han Qi, M.D., +86-02087343895, qihan@sysucc.org.cn
About this study
Official title: Transjugular Intrahepatic Portosystemic Shunt (TIPS) Plus Half-dose Donafenib (a Kind of Anti-angiogenesis Agents) in Advanced HCC with Tumor Thrombosis-associated Portal Hypertension: a Prospective, Single-arm, Phase II Study. (DoTH Study)
The purpose of this study is to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) plus half-dose donafenib (a kind of anti-angiogenesis agents) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension.
Read the detailed description
This is a prospective, single-arm, phase II study to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) plus half-dose donafenib (a kind of anti-angiogenesis agents) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension. Subjects who meet the admission criteria will be treated with half-dose donafenib after TIPS until disease progression, intolerable toxicity, death, withdrawal of the patient, or the researchers determined that the drug must be discontinued.
The primary outcome measure is to evaluate the objective response rate (ORR) based on mRECIST. The secondary outcome measures include the duration of response (DOR), disease control rate (DCR), the recurrence rate of portal hypertension-related haemorrhage or ascites, the median progression-free survival time (mPFS) and median overall survival time (mOS). This study also aims to assess the safety and adverse events.
- Conditions
- Hepatocellular Carcinoma with PVTT
- Being tested
- Transjugular intrahepatic portosystemic shunt (TIPS), Donafenib
- Keywords
- Transjugular intrahepatic portosystemic shunt (TIPS), Hepatocelluar Carcinoma with portal vein tumor thrombus, tumor thrombosis-associated portal hypertension, Donafenib, Combination therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transjugular intrahepatic portosystemic shunt (TIPS)Procedure or surgery
Perform transjugular intrahepatic portosystemic shunt under the guidance of DSA
DonafenibDrug
Half-dose donafenib, 100mg BID P.O. unless any evidence of disease progression or unacceptable side effects.
| Study group | Role | What they receive |
|---|---|---|
| DoTH: TIPS plus half-dose donafenib | Experimental | TIPS plus half-dose donafenib Receives: Procedure: Transjugular intrahepatic portosystemic shunt (TIPS); Drug: Donafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) by RECIST 1.1 and mRECIST
ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1 or mRECIST
Measured: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 1 year)
Secondary outcomes (5)
Overall survival (OS)
OS is measured from the start date of the TIPS until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date, whichever comes earlier, assessed up to 2 years.
Measured: From the start date of the TIPS until date of death from any cause, assessed up to 2 years.
Progression-free survival (PFS)
The progression-free survival (PFS) defined as the time from the date of TIPS to the date of first documented progression (mRECIST or RECIST v1.1) or date of death from any cause, whichever came first, assessed up to 2 years
Measured: The progression-free survival (PFS) defined as the time from the date of TIPS to the date of first documented progression (mRECIST or RECIST v1.1) or date of death from any cause, whichever came first, assessed up to 2 years
Disease control rate (DCR)
DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1 or mRECIST.
Measured: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 1 year)
Rate of portosystemic shunt stent patency
The status of the shunt stent evaluated by the color Doppler ultrasound.
Measured: 1, 3, 6, 9, 12 months after TIPS
Recurrence rate of portal hypertension-related complications
It was defined as the percentage of patients with recurrent gastrointestinal bleeding, refractory ascites, hepatic pleural effusion, and portal hypertensive gastroenteropathy within 6 months after TIPS
Measured: From date of TIPS until portal hypertension-related complications (up to 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2024
- Study start8 Oct 2024
- Primary completion31 May 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma with PVTTStudies 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
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fei Gao
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Fei Gao, Sun Yat-sen University
- Investigators
- Fei Gao, M.D.，Ph.D., Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06646198
- Sponsor's protocol ID
- DoTH
- Acronym
- DoTH
- Status last verified
- Oct 2024
- First submitted
- 14 Oct 2024
- Last updated
- 17 Oct 2024
- 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 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transjugular Intrahepatic Portosystemic Shunt (TIPS) Plus Half-dose Donafenib (a Kind of Anti-angiogenesis Agents) in Advanced HCC with Tumor Thrombosis-associated Portal Hypertension: a Prospective, Single-arm, Phase II Study. (DoTH Study)
- ClinicalTrials.gov ID
- NCT06646198
- Acronym / sponsor ID
- DoTH / DoTH
- Conditions
- Hepatocellular Carcinoma with PVTT
- Keywords
- Transjugular intrahepatic portosystemic shunt (TIPS), Hepatocelluar Carcinoma with portal vein tumor thrombus, tumor thrombosis-associated portal hypertension, Donafenib, Combination therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fei GaoUniversity, hospital or other
- Study start
- 8 Oct 2024 (actual)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 17 Oct 2024 (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 purpose of this study is to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) plus half-dose donafenib (a kind of anti-angiogenesis agents) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension.
Detailed description
This is a prospective, single-arm, phase II study to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) plus half-dose donafenib (a kind of anti-angiogenesis agents) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension. Subjects who meet the admission criteria will be treated with half-dose donafenib after TIPS until disease progression, intolerable toxicity, death, withdrawal of the patient, or the researchers determined that the drug must be discontinued.
The primary outcome measure is to evaluate the objective response rate (ORR) based on mRECIST. The secondary outcome measures include the duration of response (DOR), disease control rate (DCR), the recurrence rate of portal hypertension-related haemorrhage or ascites, the median progression-free survival time (mPFS) and median overall survival time (mOS). This study also aims to assess the safety and adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DoTH: TIPS plus half-dose donafenib | Experimental | Procedure: Transjugular intrahepatic portosystemic shunt (TIPS), Drug: DonafenibTIPS plus half-dose donafenib |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- The patient voluntarily joined the study and signed an informed consent form;
- ≥18 and ≤ 75 years old, both male and female;
- Pathologically confirmed hepatocellular carcinoma, at least one measurable focus without local treatment (according to mRECIST or RECIST 1.1 requirements;
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
- BCLC-C stage accompanied by tumor thrombosis-associated portal hypertension;
Key exclusion criteria (18 listed)
- The patient has any active autoimmune disease or a history of autoimmune disease;
- The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment;
- Severe allergic reaction to any compositions of donafenib tablets or contrast media containing iodine ;
- Central nervous system metastasis;
- Patients who have received liver transplantation in the past;
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 |
|---|---|---|
| Transjugular intrahepatic portosystemic shunt (TIPS)Perform transjugular intrahepatic portosystemic shunt under the guidance of DSA | Procedure or surgery | DoTH: TIPS plus half-dose donafenib |
| DonafenibHalf-dose donafenib, 100mg BID P.O. unless any evidence of disease progression or unacceptable side effects. | Drug | DoTH: TIPS plus half-dose donafenib |
Primary outcome
Objective response rate (ORR) by RECIST 1.1 and mRECIST
Time frame: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 1 year)
ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1 or mRECIST
5 secondary outcomes
Overall survival (OS)
Time frame: From the start date of the TIPS until date of death from any cause, assessed up to 2 years.
Progression-free survival (PFS)
Time frame: The progression-free survival (PFS) defined as the time from the date of TIPS to the date of first documented progression (mRECIST or RECIST v1.1) or date of death from any cause, whichever came first, assessed up to 2 years
Disease control rate (DCR)
Time frame: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 1 year)
Rate of portosystemic shunt stent patency
Time frame: 1, 3, 6, 9, 12 months after TIPS
Recurrence rate of portal hypertension-related complications
Time frame: From date of TIPS until portal hypertension-related complications (up to 6 months)
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 17 Oct 2024.
- 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.
Fei Gao, M.D.，Ph.D. principal investigator
Sun Yat-Sen University Cancer Center
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 Transjugular intrahepatic portosystemic shunt (TIPS) and Donafenib in people with Hepatocellular Carcinoma with PVTT, run by Fei Gao 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 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: looking for participants now, as of the sponsor's last update on 17 Oct 2024. 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?
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 Fei Gao, M.D.，Ph.D. (+86-13760869828, gaof@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) by RECIST 1.1 and mRECIST (time frame: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 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 17 Oct 2024.