TIPS Plus Cadonilimab in Advanced HCC with Tumor Thrombosis-associated Portal Hypertension:a Prospective, Single-arm, Phase II Study

NCT05882370 | Recruiting Phase 2

• 1 other identifier: SCALE
• Study Type: interventional
• Target: 30
• 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 Cadonilimab (a PD-1/CTLA-4 bispecific antibody) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension.

Conditions

Hepatocellular Carcinoma

Keywords

TIPS; Cadonilimab; Combination therapy; advanced HCC; tumor thrombosis-associated portal hypertension

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 and mRECIST

  From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)

Secondary Outcomes (5)

• 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 2 years)

• Duration of response (DOR)

  From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to 2 years)

• Overall survival rate (OSR)

  From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to 2 years)

• Progression-free survival time (mPFS)

  From date of first dose of study drug to the date of first documentation of disease progression (up to 2 years)

• Median overall survival time (mOS)

  From the start date of the Treatment Phase until date of death from any cause (up to 2 years)

Other Outcomes (1)

• Treatment-related adverse events

  From the start date of the Treatment Phase until date of death from any cause (up to 2 years)

Study Arms (1)

SCALE

EXPERIMENTAL

TIPS plus Cadonilimab

Drug: Cadonilimab; Procedure: transjugular intrahepatic portosystemic shunt (TIPS)

Interventions

Cadonilimab DRUG

Patients were treated with TIPS plus Cadonilimab (10mg/kg, intravenously, d1, Q3W) to a maximum total cycle of 18 unless any evidence of disease progression or unacceptable side effects.

SCALE

transjugular intrahepatic portosystemic shunt (TIPS) PROCEDURE

transjugular intrahepatic portosystemic shunt (TIPS)

SCALE

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;
• Clinically diagnosed or pathologically confirmed hepatocellular carcinoma, at least one measurable focus without local treatment (according to mRECIST requirements, the measurable focus spiral CT scan length ≥ 10 mm or enlargement Short diameter of lymph node ≥15 mm);
• Child-Pugh score ≤ 13 points;
• BCLC-C stage accompanied by tumor thrombosis-associated portal hypertension;
• Newly diagnosed patients who have not received targeted therapy or immunotherapy in the past;
• ECOG score: 0～1;
• Expected survival period ≥ 12 weeks;
• 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≥1.5×109/L; Platelet ≥50×109/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;
• 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;
• The number of system treatment lines ≥ 2 lines;
• Severe allergic reaction to other monoclonal antibodies;
• Those with a known history of central nervous system metastasis or hepatic encephalopathy;
• 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 cancer thrombus, etc.;
• Suffer from high blood pressure and cannot be well controlled by antihypertensive 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;
• Patients who have previously received radiotherapy, chemotherapy, hormone therapy, and surgery, after the completion of the treatment (last medication) and less than 4 weeks before the study medication; molecular targeted therapy (including other oral targeted drugs used in clinical trials) is less than the first study medication \<5 drug half-lives, or patients whose adverse events (except alopecia) caused by previous treatment have not recovered to ≤ CTCAE level 1;
• 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);

Sponsors & Collaborators

• Fei Gao: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Portasystemic Shunt, Transjugular Intrahepatic

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

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

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: May 22, 2023
• First Posted: May 31, 2023
• Study Start: December 1, 2022
• Primary Completion: June 30, 2025
• Study Completion: August 31, 2025
• Last Updated: October 16, 2024

Record last verified: 2024-10

Locations

CN (1)