Clinical trial NCT05833126: Hepatic Arterial Infusion Chemotherapy in Combination With Atezolizumab and Bevacizumab for Second-line Treatment of Patients With Recurrent Liver Cancer After Liver Transplantation
Official title: Hepatic Arterial Infusion Chemotherapy in Combination With Atezolizumab and Bevacizumab for Second-line Treatment of Patients With Recurrent Liver Cancer After Liver Transplantation: an Open-label, Prospective, Single-center, Single-arm Clinical Study Protocol
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Liver Cancer After Liver Transplantation
Keywords: Atezolizumab
Bevacizumab
Hepatic arterial infusion chemotherapy
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2023-04-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: For patients with recurrent liver cancer after liver transplantation, the median survival time is low and the prognosis is often poor. On the one hand, it is necessary to take into account the weakened effect of postoperative anti-rejection drugs with the use of immune checkpoint inhibitors, and on the other hand, the therapeutic effect of recurrent tumors should be taken into account. Both HAIC (hepatic arterial infusion chemotherapy) and T+A（Bevacizumab+Atezolizumab) have inhibitory effects on tumor, and we consider combining them organically to explore one that not only has a good inhibitory effect on tumor, but also better reduces the risk and degree of rejection. Therefore, in order to determine the feasibility and effectiveness of hepatic arterial infusion chemotherapy combined with Atezolizumab and Bevacizumab in the second-line treatment of patients with recurrent liver cancer after liver transplantation


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years old, ≤75 years old, gender unlimited;
2. hepatocellular carcinoma confirmed by pathology after liver transplantation;
3. CT and/or MRI confirmed tumor recurrence or metastasis, and the tumor recurrence and metastasis were not suitable for radical treatment such as surgical resection or ablation after multidisciplinary evaluation, and disease progression occurred after one first-line treatment regimen without immunotherapy;
4. There is at least one measurable recurrent or metastatic tumor lesion;
5. The expected survival time is more than 3 months;
6. Child-Pugh grade A and B (≤7 points);
7. Function of other vital organs: absolute neutrophil count ≥1.5×10E9/L; Platelet ≥50×10 e9 / L; Hemoglobin ≥9 g/dL; Serum albumin ≥2.8g/dL; Thyroid stimulating hormone (TSH)≤1 ULN(if TSH is abnormal, both T3 and T4 levels should be checked. If the levels of T3 and T4 were normal, the patients could be enrolled); Bilirubin ≤ 1.5x ULN; ALT and AST≤3 times ULN; Serum creatinine ≤1.5 ULN;
8. ECOG scored 0-2 points;
9. The patient fully understands and voluntarily signs the informed consent, and is willing and able to comply with the requirements of visit, treatment plan, laboratory examination and other requirements of the study schedule.

Exclusion Criteria:

1. Positive expression of PD-L1 in immunohistochemical liver biopsy (parenchymal or non-parenchymal cells of liver);
2. Allergic to bevacizumab and Atezolizumab;
3. ≥ grade II myocardial ischemia or myocardial infarction;
4. The hypertensive drugs cannot be controlled to the normal level (systolic blood pressure \> 140mmHg, diastolic blood pressure \> 90mmHg); Abnormal coagulation function (PT\>16s, APTT\>43s, TT\>21s, Fbg \<2g/L), a history of gastrointestinal bleeding within 6 months;
5. Patients with high risk of bleeding or receiving thrombolytic or anticoagulant treatment;
6. Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, psoriasis, etc.;
7. The primary liver disease of liver transplantation was autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis;
8. interstitial pneumonia and other lung diseases, poor lung function;
9. Participate in clinical trials of other experimental drugs within 4 weeks;
10. infections requiring systemic treatment;
11. human immunodeficiency virus (HIV) positive infection;
12. Other factors that may affect safety or compliance;
13. During treatment of acute rejection or within 1 month after treatment;
14. Poor compliance.

Primary outcomes:
measure: Acute graft rejection rate
timeFrame: 3 months
measure: Objective Response Rate
timeFrame: 1 year
Secondary outcomes:
measure: Overall Survival
timeFrame: 1 year
measure: Progression-free Survival
timeFrame: 1 year
measure: Time to Progression
timeFrame: 1 year
measure: Serious Adverse Event
timeFrame: 1 year
measure: Graft Rejection
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Liver Transplantation, the Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Shuhong Yi
role: STUDY_DIRECTOR
References: