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)
Overview
- Phase
- Phase 2
- Intervention
- Transjugular intrahepatic portosystemic shunt (TIPS)
- Conditions
- Hepatocellular Carcinoma with PVTT
- Sponsor
- Fei Gao
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR) by RECIST 1.1 and mRECIST
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief 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.
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.
Investigators
Fei Gao
Clinical Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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;
- •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.
Exclusion Criteria
- •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;
- •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;
Arms & Interventions
DoTH: TIPS plus half-dose donafenib
TIPS plus half-dose donafenib
Intervention: Transjugular intrahepatic portosystemic shunt (TIPS)
DoTH: TIPS plus half-dose donafenib
TIPS plus half-dose donafenib
Intervention: Donafenib
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Overall survival (OS)(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)
- Disease control rate (DCR)(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(1, 3, 6, 9, 12 months after TIPS)
- Recurrence rate of portal hypertension-related complications(From date of TIPS until portal hypertension-related complications (up to 6 months))