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

Early Phase 1

• Conditions: Hepatocellular Carcinoma Stage IIIa
• Interventions: Drug: Lenvatinib; Drug: mFOLFOX regimen; Drug: ROX regimen

• Registration Number: NCT05007587
• Lead Sponsor: Zhejiang Cancer Hospital

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.

Study Timeline

• Status Verified: 2021-06
• Study Start: 2021-07-01
• Study First Submitted: 2021-07-21
• Study First Submitted QC: 2021-08-12
• Last Update Submitted: 2021-08-12
• Study First Posted: 2021-08-16
• Last Update Posted: 2021-08-16
• Primary Completion: 2022-06-30
• Study Completion: 2023-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lenvatinib，Then HAIC of mFOLFOX regimen	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.
Lenvatinib，Then HAIC of ROX regimen	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.
Lenvatinib，Then HAIC of ROX regimen	Lenvatinib	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.
Lenvatinib，Then HAIC of mFOLFOX regimen	Lenvatinib	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

The Cancer Hospital of the University of Chinese Academy of Sciences（Zhejiang Cancer Hospital）; 🇨🇳 Hangzhou, Zhejiang, China