Hepatocellular Carcinoma Stage IIIa
Conditions
Keywords
Lenvatinib, HAIC, HCC
Brief summary
Lenvatinib Plus Hepatic Arterial Infusion of Modified FOLFOX Regime vs Lenvatinib Plus Hepatic Arterial Infusion of Oxaliplatin Plus Raltitrexed in Patients with Advanced Hepatocellular Carcinoma
Detailed description
Hepatic arterial infusion chemotherapy is one of the important means for the treatment of advanced liver cancer. A multicenter randomized controlled study has confirmed that modified FOLFOX hepatic arterial infusion chemotherapy can significantly improve the prognosis of patients with advanced liver cancer and prolong the survival period of patients. The 2020 edition of CSCO guidelines for the diagnosis and treatment of liver cancer has recommended oxaliplatin based FOLFOX arterial infusion regimen as the first-line treatment of advanced liver cancer. FOLFOX regimen is safe and effective, but fluorouracil needs more than 46 hours of long-term infusion, patients have difficulty in moving during catheterization, and increase the risk of thrombosis, so it is urgent to find a short-term infusion of fluorouracil. As a new antimetabolic drug, raltitrexed can be used for short-term infusion, and its plasma concentration half-life is longer than that of fluorouracil. Previous studies have shown that compared with FOLFOX arterial infusion regimen, oxaliplatin combined with raltitrexed regimen has longer overall survival (OS) and progression free survival (PFS) in the treatment of advanced liver cancer. In addition, as an advanced liver cancer, lenvastinib has been recommended as a targeted drug for the first-line treatment of advanced HCC. This study intends to explore the efficacy and safety of modified FOLFOX regimen compared with oxaliplatin combined with raltitrexed (Rox regimen) in the treatment of lenvastinib combined with HAIC, so as to provide more clinical schemes for further improving the survival rate of patients with advanced liver cancer.
Interventions
DRUGLenvatinib
8mg lenvatinib (weight\<60kg) or 12mg lenvatinib (weight\>60kg) QD
DRUGmFOLFOX regimen
HAIC was performed every 3 weeks. The mFOLFOX regimen was administered via hepatic artery: oxaliplatin , 85mg/m2 , from hour 0 to 2 on day1 ; leucovorin , 400mg/m2 , from hour 2 to 3 on day 1 ; fluorouracil , 400mg/m2 , bolus at hour 3 ; and 2400mg/m2 over 46 hours on days 1 and 2.3mg/m2 , from hour 4 to 5 on day 1.
DRUGROX regimen
HAIC was performed every 3 weeks. The ROX regimen was administered via hepatic artery: oxaliplatin , 100mg/m2 , from hour 0 to 4 on day1 ;raltitrexed , 3mg/m2 , from hour 4 to 5 on day 1.
Sponsors
First Affiliated Hospital of Zhejiang University
First Affiliated Hospital of Wenzhou Medical University
Second Affiliated Hospital of Wenzhou Medical University
Shaoxing People's Hospital
The Third Affiliated Hospital of Wenzhou Medical University
Jinhua Central Hospital
Zhejiang Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
60 HCC participants were divided into test group and control group by random drawing
Intervention model description
Prospective, multi-center, randomized controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntary participation and informed consent, aged 18-75; 2. Patients with HCC confirmed by histopathology or meeting the clinical diagnostic criteria in the 2019 edition of the diagnostic and therapeutic criteria for primary liver cancer; 3. BCLC stage C patients with vascular invasion and without extrahepatic metastasis; 4. Child Pugh liver function classification: A or B grade; 5. ECOG physical strength score was 0-2 points; 6. No previous systemic or local treatment, and the expected survival time is more than 3 months; 7. According to recist1.1, the patient must have at least one measurable target lesion that has passed CT or MRI examination, and the tumor imaging evaluation was conducted within 2 weeks before receiving the study drug; 8. Full organ and bone marrow function: WBC ≥ 3.0 × 109/L； NE≥1.5 × 109/L； PLT≥75 × 109/L； Liver and kidney function ALT and AST ≤ 5uln; TBIL≤2ULN； Albumin ≥ 28g / L; Cr≤1.5 ULN； International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) exceeding the normal control range ≤ 4 seconds;
Exclusion criteria
1. Hepatocholangiocarcinoma, mixed cell carcinoma and fibrolamellar cell carcinoma are known; 2. Uncontrollable ascites, hepatic encephalopathy or esophageal variceal bleeding; 3. Patients with hypertension who can not be reduced to normal range after antihypertensive drug treatment (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg); 4. Patients with myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia, myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia (QTc interval ≥ 450 ms) (QTc interval was calculated by fridericia formula); 5. Patients with history of gastrointestinal bleeding or definite tendency of gastrointestinal bleeding in the past 3 months, such as esophageal varices with bleeding risk, local active ulcer lesions, fecal occult blood ≥ +, can not be included in the group; 6. Pregnant or lactating women, patients with fertility are unwilling or unable to take effective contraceptive measures; 7. patients with a history of HIV infection; 8. The researcher judges other situations that may affect the clinical research and the judgment of research results;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate and Disease Control Rate of the HCC Participants | from admission to discharge, up to 4 weeks | ORR and DCR are validated indicators of the short-term clinical effects of hepatocellular carcinoma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival and Progression-free Survival of the HCC Participants | six months and twelve months | OS and PFS are validated indicators of the long-term clinical effects of hepatocellular carcinoma |
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | from admission to discharge, up to 4 weeks | Treatment-Related Adverse Events are important indicators of the safety for tumor treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| ECOG score | from admission to discharge, up to 1 week | ECOG score is divided into 0,1,2 |
| Tumor size | from admission to discharge, up to 1 week | Tumor size is divided into \>10cm and ≤10cm |
| Tumor number | from admission to discharge, up to 1 week | Tumor number is divided into single and multiple |
| Weight and Height | from admission to discharge, up to 1 week | Weight and Height will be combined to report BMI in kg/m\^2 |
| Portal vein invasion | from admission to discharge, up to 1 week | Portal vein invasion is divided into Vp1-2, Vp3, Vp4 |
| Extrahepatic spread | from admission to discharge, up to 1 week | Extrahepatic spread is divided into Yes and No |
| Hepatitis B infection | from admission to discharge, up to 1 week | Hepatitis B infection is divided into Yes and No |
| AFP | from admission to discharge, up to 1 week | AFP is divided into \>1000ug/L and ≤1000ug/L |
| Age | from admission to discharge, up to 1 week | Age is divided into \>50 and ≤50 |
| Sex | from admission to discharge, up to 1 week | Sex is divided into Male and Female |
Countries
China
Outcome results
None listed