Recurrent Liver Cancer After Liver Transplantation
Conditions
Keywords
Atezolizumab, Bevacizumab, Hepatic arterial infusion chemotherapy
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
Interventions
DRUGHepatic arterial infusion chemotherapy + Atezolizumab and bevacizumab
Drug: Oxaliplatin, calcium folinate, 5-FU, Atezolizumab and bevacizumab Procedure: HAIC
Sponsors
Shuhong Yi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute graft rejection rate | 3 months | defined as the incidence of acute graft rejection after HAIC combined with T+A. |
| Objective Response Rate | 1 year | defined as the treatment response assessed by mRECIST after HAIC combined with T+A treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | 1 year | defined as the time from the start of HAIC combined with T+A treatment to tumor progression or death from any cause. |
| Overall Survival | 1 year | defined as the time from HAIC combined with T+A treatment to patient death from any cause. |
| Graft Rejection | 1 year | defined as the incidence of transplant rejection during HAIC combined with T+A treatment. |
| Serious Adverse Event | 1 year | The incidence of serious adverse events caused by HAIC combined with T+A treatment. |
| Progression-free Survival | 1 year | defined as the time from the start of HAIC combined with T+A treatment to the onset of tumor Progression or death from any cause. |
Countries
China
Contacts
Primary ContactHua Li, MD&PhD
Backup ContactSiqi Li, MD&PhD
Outcome results
None listed