Single Arm, Prospective, Multicenter Clinical Study of TACE With Adebrelimab and Bevacizumab for Unresectable Hepatocellular Carcinoma

Обзор

To evaluate the efficacy and safety of TACE combined with adebrelimab and bevacizumab transformation in unresectable hepatocellular carcinoma

Вмешательства

• Препарат TACE with adebrelimab and bevacizumab
  TACE treatment once; Adebrelimab: 20mg/kg, every 3 weeks (21 days); Bevacizumab; 15mg/kg, every 3 weeks (21 days);

Первичные конечные точки

• Objective response rate（ORR） [Срок оценки: Up to 2 years]
• Occurence of AE and SAE [Срок оценки: Up to 2 years]

Вторичные конечные точки (8)

• Radical (R0) resection rate after conversion therapy [Срок оценки: Up to 2 years]
• percent conversion [Срок оценки: Up to 2 years]
• Pathological complete response rate (pCR) [Срок оценки: Up to 2 years]
• Major pathological response rate (MPR) [Срок оценки: Up to 2 years]
• Progression-free survival (PFS) [Срок оценки: Up to 2 years]
• Disease control rate（DCR） [Срок оценки: Up to 2 years]
• Relapse-free survival time (RFS) [Срок оценки: Up to 2 years]
• Overall survival（OS） [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Age: 18 \~ 75, both male and female；
• Strictly comply with the primary liver cancer diagnosis and treatment standard (2022 edition) clinical diagnosis criteria or primary hepatocellular carcinoma diagnosed by pathological histology or cytology examination, and at least one measurable lesions (according to the RECIST1.1 standard, the spiral CT scan of 10mm or short diameter of 15mm）；
• Patients without previous systematic treatment and inoperable resection / radical ablation surgery, but who can tolerate TACE;
• The CNLC stage is Ⅱa-Ⅲb stage;
• The Child-Pugh grade of liver function is A grade or B grade (5-7 points);
• The ECOG PS score is 0-1 points;
• Expected survival period of 12 weeks;
• If the patient has active hepatitis B virus (HBV) infection: HBV-deoxyribonucleic acid (DNA) must be <2000 IU / mL (if the study site has only copy / mL testing units, Must be <12500 copy / mL), And received at least 14 days before initiating anti-HBV treatment (according to local standard therapy, e. g. entecavir) and willing to receive antiviral treatment throughout the study; hepatitis C virus (HCV) ribonucleic acid (RNA) positive patients must receive antiviral treatment according to local standard treatment guidelines and liver function within grade CTCAE 1 elevation;
• Main organs function are normal and meet the following criteria: (1) The blood routine examination standards should be met with: (no blood transfusion within 14 days) A. Hemoglobin (HB), 90g / L, B. White blood cell count (WBC) 3109 / L C. Absolute neutrophil count (ANC) 1.5109 / L, D. Platelet (PLT) 80109 / L;(2) Biochemical examination shall meet the following standards: A. Bilirubin (BIL) <1.5 times the upper limit of normal value (ULN); B. Glutamic gamma aminotransferase (ALT) and glutamate aminotransferase AST <5 ULN; C. Serum creatinine (Cr)≤1.5ULN；
• Women of childbearing age must have negative pregnancy test (serum) or urine HCG within 7 days before enrollment and are willing to use appropriate contraception during treatment and 24 weeks after the last administration of test drug; for men, surgical sterilization or agree to use appropriate contraception during and 24 weeks after the last administration of trial drug;
• The subjects volunteered to join the study and had good compliance with the follow-up.

Критерии исключения

• Pregnant or lactating women;
• The pathology is clearly cholangiocytic carcinoma or mixed cell carcinoma;
• Diffuse liver cancer;
• Patients with autoimmune diseases, organ / hematopoietic stem cell transplantation or other malignant tumors (except for cured basal skin cell carcinoma and cervix carcinoma in situ);
• Patients with consciousness disorders or unable to cooperate with the treatment, combined with patients with mental illness;
• Patients who have participated in other clinical trials in the recent three months;
• Previous history of other malignancies or have received targeted therapy and other PD-1 / PD-L1 inhibitor therapy;
• Received major surgery or chemotherapy or other systemic therapy for target lesions (including not limited to radiation therapy, ablation therapy, etc.) within 1 month prior to enrollment;
• Use of immunosuppressants or systemic hormone therapy within 14 days before enrollment to achieve immunosuppressive purposes (dose> 10mg / day prednisone or other efficacy hormones);
• Liver function was graded as Child-Pugh C, which could not be improved by liver care treatment；
• esophageal (gastric fundus) varices rupture and bleeding within 1 month before treatment；
• Uncorrectable coagulopathy and severe blood abnormalities, with severe bleeding tendency. Platelet count <50109 / L and severe coagulation abnormalities against surgery (anticoagulation therapy and / or anticoagulant therapy should be stopped for more than 1 week before radiation therapy);
• A stubborn amount of ascites, pleural fluid, malignant fluid;
• Active infection, especially the inflammation of the biliary tract system;
• Severe functional failure of the liver, kidney, heart, lung, brain and other major organs;
• Previously allergic to PD-1 / PD-L1 mAb / any component of the targeted drug or other similar trials;
• Patients with hypertension who cannot be reduced to the normal range by antihypertensive medication (systolic blood pressure> 140 mmHg, diastolic blood pressure> 90 mmHg);
• Previous severe cardiovascular disease, including but not limited to the following diseases: myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including 450 ms in QTc men and 470 ms in women); cardiac dysfunction by NYHA, or cardiac ultrasound indicating left ventricular ejection fraction (LVEF) <50%;
• Patients with positive urinary protein (urinary protein test of 2 + or above, or 24-hour urinary protein quantification of> 1.0g);
• Failure to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption;
• According to the discretion of the investigator, patients with other concomitant diseases that seriously endanger patient safety or affect the completion of the study;
• Patients with radiotherapy, targeted therapy, and other contraindications to immunotherapy.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Xiamen University — Xiamen

Идентификаторы

NCT: NCT05970666 · 23-OBU-FJ-HCC-II-012

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗