TACE Combined With Lenvatinib for Unresectable Hepatocellular Carcinoma (Prolong)

TACE Combined With Lenvatinib for Unresectable Hepatocellular Carcinoma：A Multicenter, Single-armed, Prospective, Observational Study (Prolong)

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.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Lenvatinib; Procedure: TACE

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 Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Unrecestable CNLC stage IIb-IIIb HCC patients

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lenvatinib and TACE; Patients in Lenvatinib + TACE group will take oral lenvatinib within ten days after TACE.	Drug: Lenvatinib; Lenvatinib capsules will be administered orally, once daily (for patients <60kg, lenvatinib 8mg po; for patients ≥60kg, lenvatinib 12mg po); Procedure: TACE; TACE will be performed as needed.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrahepatic ORR and Extrahepatic ORR	The percentage of patients who have best overall response of complete response (CR) or partial response (PR) according to mRECIST intrahepatic or extrahepatic, respectively.	up to 12 months
Progression-free survival (PFS)	The time from the beginning of treatment of TACE to the time of tumor progression or death from any cause (according to mRECIST standard)	up to 12 months
Alpha-fetoprotein (AFP) response rate	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.	up to 12 months
Time to progression（TTP）	The time from the beginning of treatment of TACE to the time of tumor progression. (according to mRECIST standard)	up to 12 months
Adverse events(AEs)	AEs(adverse events) evaluated by the CTC-AE 5.0	up to 18 months

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Investigators: Study Chair: Guoliang Shao, Professor, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 30, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): August 31, 2022

Study Registration Dates

• First Submitted: September 10, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 23, 2020

Study Record Updates

• Last Update Posted (Actual): September 23, 2020
• Last Update Submitted That Met QC Criteria: September 22, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Lenvatinib; Carcinoma, Hepatocellular; Transarterial chemoembolization
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: Prolong

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No