TIPS Plus Half-dose Donafenib in AHCC with PVTT-associated Portal Hypertension

NCT06646198 | Recruiting Phase 2

• 1 other identifier: DoTH
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

  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)

  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)

Other Outcomes (1)

• Treatment-related adverse events

  From the start date of the Treatment Phase until date of death from any cause (up to 1 year)

Study Arms (1)

DoTH: TIPS plus half-dose donafenib

EXPERIMENTAL

TIPS plus half-dose donafenib

Procedure: Transjugular intrahepatic portosystemic shunt (TIPS); Drug: Donafenib

Interventions

Transjugular intrahepatic portosystemic shunt (TIPS) PROCEDURE

Perform transjugular intrahepatic portosystemic shunt under the guidance of DSA

DoTH: TIPS plus half-dose donafenib

Donafenib DRUG

Half-dose donafenib, 100mg BID P.O. unless any evidence of disease progression or unacceptable side effects.

DoTH: TIPS plus half-dose donafenib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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;
• 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；

Sponsors & Collaborators

• Fei Gao: lead

Study Sites (1)

Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

Portasystemic Shunt, Transjugular Intrahepatic; donafenib

Intervention Hierarchy (Ancestors)

Portasystemic Shunt, Surgical; Anastomosis, Surgical; Surgical Procedures, Operative; Vascular Grafting; Vascular Surgical Procedures; Cardiovascular Surgical Procedures

Study Officials

• Fei Gao, M.D.，Ph.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fei Gao, M.D.，Ph.D.

CONTACT

+86-13760869828; gaof@sysucc.org.cn

Han Qi, M.D.

CONTACT

86-15920316143; qihan@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 17, 2024
• Study Start: October 8, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)