TACE Combined With Lenvatinib for Unresectable Hepatocellular Carcinoma (Prolong)

• Conditions: Carcinoma, Hepatocellular
• Interventions: Drug: Lenvatinib; Procedure: TACE

• Registration Number: NCT04560751
• Lead Sponsor: Zhejiang Cancer Hospital

Brief Summary

This is a multicenter, prospective, observational study in which subjects will be treated with lenvatinib combined with TACE in un-resectable HCC patients who had not received systematic treatment or TACE treatment in the past.

Detailed Description

Only 30% of HCC patients received radical resection. Most of the patients are in the advanced stage and can only receive palliative treatment such as TACE or systemic treatment. Lenvatinib is a multi-target receptor tyrosine kinase inhibitor (TKI), which mainly inhibits vascular endothelial growth factor(VEGF) receptor-1, 2, 3; fibroblast growth factors(FGF) receptor-1, 2, 3, 4; platelet derived growth factor receptor(PDGFR)α; RET and KIT and showed significant anti-tumor effect in REFLECT study. The purpose of this study is to explore the efficacy and safety of Lenvatinib and TACE in unresectable HCC patients.

Study Timeline

• Status Verified: 2020-09
• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-09-22
• Last Update Submitted: 2020-09-22
• Study First Posted: 2020-09-23
• Last Update Posted: 2020-09-23
• Study Start: 2020-09-30
• Primary Completion: 2021-12-31
• Study Completion: 2022-08-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Ages of ≥ 18 and ≤ 75 years old.
2. Clinically or histopathologically diagnosed as hepatocellular carcinoma (HCC).
3. China stage IIb-IIIb patients, not suitable for surgical resection.
4. The imaging examination within 2 weeks before interventional therapy showed that there was at least one target lesion that could be measured by CT or MRI, and the lesion was suitable for repeated and accurate measurement.
5. Child-Pugh scores ≤7.
6. ECOG：0-1.
7. Intended to be treated with TACE combined with lenvatinib.
8. Good organ and bone marrow function: Blood routine: WBC>4.0×109/L、Hb>80g/L, PLT>75×109/L, NEUT>1.5×10⁹/L. Blood coagulation function: International normalized ratio (INR)<1.2. Hepatic function: serum albumin (ALB)>3.5 g/dl, total bilirubin (TBIL) <1.5 × normal upper limit (ULN) (Eliminate biliary obstruction), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 × ULN. Renal dysfunction：serum creatinine (SCR) <1.5× ULN.
9. Agreed to join the clinical trial and sign the informed consent form.

Exclusion Criteria

1. Hepatobiliary cell carcinoma, mixed cell carcinoma and fibrolamellar hepatocellular carcinoma.
2. With invasion of the main portal vein or vena cava.
3. Received interventional therapy such as TACE within 2 years.
4. Received systematic treatment in the past.
5. Uncontrollable ascites, hepatic encephalopathy or esophagogastric variceal bleeding.
6. Patients with hypertension who cannot be reduced to normal range after antihypertensive treatment (systolic blood pressure > 140mmHg, or diastolic blood pressure > 90 mmHg).
7. Suffering from grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmia or myocardial ischemia or myocardial infarction (The QTc interval ≥ 450ms, QTc interval is calculated by Fridericia formula).
8. There is a history of gastrointestinal bleeding or a clear tendency of gastrointestinal bleeding in the past 3 months, such as esophageal varices at risk of bleeding, local active ulcer lesions, fecal occult blood ≥ (+).
9. Pregnant or lactating women. A fertile patient who is unwilling or unable to use effective contraception.
10. Patients with HIV infection.
11. Suspected allergy to research drugs.
12. Other situations which the researchers considered ineligible for participating in the trial.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Lenvatinib and TACE	TACE	Patients in Lenvatinib + TACE group will take oral lenvatinib within ten days after TACE.
Lenvatinib and TACE	Lenvatinib	Patients in Lenvatinib + TACE group will take oral lenvatinib within ten days after TACE.

Primary Outcome Measures

Name	Time	Method
Objective response rate（ORR）	up to 12 months	The percentage of patients who have best overall response of complete response (CR) or partial response (PR) according to mRECIST.

Secondary Outcome Measures

Name	Time	Method
Intrahepatic ORR and Extrahepatic ORR	up to 12 months	The percentage of patients who have best overall response of complete response (CR) or partial response (PR) according to mRECIST intrahepatic or extrahepatic, respectively.
Progression-free survival (PFS)	up to 12 months	The time from the beginning of treatment of TACE to the time of tumor progression or death from any cause (according to mRECIST standard)
Alpha-fetoprotein (AFP) response rate	up to 12 months	A decrease in AFP of more than 20% in AFP+ patients treated with lenvatinib is defined as an AFP response.AFP response rate defined as the percentage of AFP response patients in all AFP positive patients.
Time to progression（TTP）	up to 12 months	The time from the beginning of treatment of TACE to the time of tumor progression. (according to mRECIST standard)
Adverse events(AEs)	up to 18 months	AEs(adverse events) evaluated by the CTC-AE 5.0