Clinical trial NCT04560751: TACE Combined With Lenvatinib for Unresectable Hepatocellular Carcinoma (Prolong)
Official title: TACE Combined With Lenvatinib for Unresectable Hepatocellular Carcinoma：A Multicenter, Single-armed, Prospective, Observational Study (Prolong)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Carcinoma, Hepatocellular
Keywords: Transarterial chemoembolization
Lenvatinib
Carcinoma, Hepatocellular
Lead sponsor: Zhejiang Cancer Hospital
Sponsor class: OTHER
First posted: 2020-09-23
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Unrecestable CNLC stage IIb-IIIb HCC patients

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate（ORR）
timeFrame: up to 12 months
Secondary outcomes:
measure: Intrahepatic ORR and Extrahepatic ORR
timeFrame: up to 12 months
measure: Progression-free survival (PFS)
timeFrame: up to 12 months
measure: Alpha-fetoprotein (AFP) response rate
timeFrame: up to 12 months
measure: Time to progression（TTP）
timeFrame: up to 12 months
measure: Adverse events(AEs)
timeFrame: up to 18 months
Other outcomes:
Locations:
Study officials:
affiliation: Zhejiang Cancer Hospital
name: Guoliang Shao, Professor
role: STUDY_CHAIR
References: