Trial Title:
TIPS Plus Cadonilimab in Advanced HCC with Tumor Thrombosis-associated Portal Hypertension:a Prospective, Single-arm, Phase II Study
NCT ID:
NCT05882370
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Hypertension, Portal
Hypertension
Thrombosis
Conditions: Keywords:
TIPS
Cadonilimab
Combination therapy
advanced HCC
tumor thrombosis-associated portal hypertension
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab
Description:
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.
Arm group label:
SCALE
Intervention type:
Procedure
Intervention name:
transjugular intrahepatic portosystemic shunt (TIPS)
Description:
transjugular intrahepatic portosystemic shunt (TIPS)
Arm group label:
SCALE
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.
Detailed description:
This is a prospective, single-arm, phase II study 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. Subjects who meet the admission criteria
will be treated with Cadonilimab 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). The
secondary outcome measures include the duration of response (DOR), disease control rate
(DCR), overall survival rate (OSR) in 6- and 12-months, the median progression-free
survival time (mPFS) and median overall survival time (mOS). This study also aims to
assess the safety and adverse events.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The patient voluntarily joined the study and signed an informed consent form;
2. ≥18 and ≤ 75 years old, both male and female;
3. 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);
4. Child-Pugh score ≤ 13 points;
5. BCLC-C stage accompanied by tumor thrombosis-associated portal hypertension;
6. Newly diagnosed patients who have not received targeted therapy or immunotherapy in
the past;
7. ECOG score: 0～1;
8. Expected survival period ≥ 12 weeks;
9. 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):
10. 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;
11. 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.
Exclusion Criteria:
1. The patient has any active autoimmune disease or a history of autoimmune disease;
2. 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;
3. The number of system treatment lines ≥ 2 lines;
4. Severe allergic reaction to other monoclonal antibodies;
5. Those with a known history of central nervous system metastasis or hepatic
encephalopathy;
6. Patients who have received liver transplantation in the past;
7. Tumor thrombus beyond the portal vein range, such as hepatic vein, inferior vena
cava, right atrium, splenic vein, superior mesenteric vein cancer thrombus, etc.;
8. Suffer from high blood pressure and cannot be well controlled by antihypertensive
drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
9. 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);
10. 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;
11. Child-Pugh score >13 points;
12. 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;
13. 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;
14. 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;
15. 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);
16. Moderate to severe pulmonary hypertension, pulmonary artery pressure was assessed by
ultrasound >40mmHg；
17. 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);
18. Central nervous system metastasis；
19. 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;
20. Live vaccine may be vaccinated less than 4 weeks before study medication or may be
administered during the study period;
21. 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 serious laboratory tests 22. Abnormalities,
accompanied by family or social factors, will affect the safety of patients.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Fei Gao, Doctor
Phone:
+86-13760869828
Email:
gaof@sysucc.org.cn
Contact backup:
Last name:
Han Qi, Doctor
Phone:
+86-02087343895
Email:
qihan@sysucc.org.cn
Contact backup:
Last name:
Fei Gao, Doctor
Start date:
December 1, 2022
Completion date:
August 31, 2025
Lead sponsor:
Agency:
Fei Gao
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05882370
