Lenvatinib Plus HAIC of Modified FOLFOX Regime vs Lenvatinib Plus HAIC of ROX Regime in Patients With Advanced HCC

Sponsor

Zhejiang Cancer Hospital (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05007587

Collaborator

First Affiliated Hospital of Zhejiang University (Other), First Affiliated Hospital of Wenzhou Medical University (Other), Second Affiliated Hospital of Wenzhou Medical University (Other), Shaoxing People's Hospital (Other), The Third Affiliated Hospital of Wenzhou Medical University (Other), Jinhua Central Hospital (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Stage IIIa	Drug: Lenvatinib Drug: mFOLFOX regimen Drug: ROX regimen	Early Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, multi-center, randomized controlled studyProspective, multi-center, randomized controlled study

Masking:

Single (Participant)

Masking Description:

60 HCC participants were divided into test group and control group by random drawing

Primary Purpose:

Treatment

Official Title:

Lenvatinib Combined With Hepatic Arterial Infusion of Modified FOLFOX Regimen Versus Lenvatinib Combined With Hepatic Arterial Infusion of ROX Regimen in the Treatment of Advanced Hepatocellular Carcinoma

Actual Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenvatinib，Then HAIC of mFOLFOX regimen Cohort1：Participants were treated with 8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) orally once daily on days 1 through 21, and HAIC regimen 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.	Drug: Lenvatinib 8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) QD Other Names: LENVIMA Drug: mFOLFOX 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. Other Names: Oxaliplatin+Leucovorin+Fluorouracil
Experimental: Lenvatinib，Then HAIC of ROX regimen Cohort2：Participants were treated with 8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) orally once daily on days 1 through 21, and HAIC regimen 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.	Drug: Lenvatinib 8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) QD Other Names: LENVIMA Drug: ROX 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. Other Names: Raltitrexed+Oxaliplatin

Arm

Intervention/Treatment

Experimental: Lenvatinib，Then HAIC of mFOLFOX regimen

Cohort1：Participants were treated with 8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) orally once daily on days 1 through 21, and HAIC regimen 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.

Drug: Lenvatinib

8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) QD

Other Names:

LENVIMA

Drug: mFOLFOX 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.

Other Names:

Oxaliplatin+Leucovorin+Fluorouracil

Experimental: Lenvatinib，Then HAIC of ROX regimen

Cohort2：Participants were treated with 8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) orally once daily on days 1 through 21, and HAIC regimen 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.

Drug: Lenvatinib

8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) QD

Other Names:

LENVIMA

Drug: ROX 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.

Other Names:

Raltitrexed+Oxaliplatin

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

Weight and Height [from admission to discharge, up to 1 week]
Weight and Height will be combined to report BMI in kg/m^2
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
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
AFP [from admission to discharge, up to 1 week]
AFP is divided into >1000ug/L and ≤1000ug/L
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Voluntary participation and informed consent, aged 18-75;
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;
BCLC stage C patients with vascular invasion and without extrahepatic metastasis;
Child Pugh liver function classification: A or B grade;
ECOG physical strength score was 0-2 points;
No previous systemic or local treatment, and the expected survival time is more than 3 months;
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;
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:

Hepatocholangiocarcinoma, mixed cell carcinoma and fibrolamellar cell carcinoma are known;
Uncontrollable ascites, hepatic encephalopathy or esophageal variceal bleeding;
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);
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);
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;
Pregnant or lactating women, patients with fertility are unwilling or unable to take effective contraceptive measures;
patients with a history of HIV infection;
The researcher judges other situations that may affect the clinical research and the judgment of research results;