Efficacy and Safety of Lenvatinib as an Adjuvant Therapy for Hepatocellular Carcinoma

Phase 2

• Conditions: Hepatocellular Carcinoma (HCC)
• Interventions: Drug: Lenvima 4 mg Oral Capsule

• Registration Number: NCT04227808
• Lead Sponsor: Shanghai Zhongshan Hospital

Brief Summary

Lenvatinib is the standard of care for patients with advanced hepatocellular carcinoma (HCC). The aim of the single-arm, open-label, phase II clinical trial is to evaluate the efficacy and safety of lenvatinib as an adjuvant therapy for patients underwent radical resection of HCC with a high risk of tumor recurrence.

Investigator hypothesize that lenvatinib may be an effective adjuvant treatment for HCC, and 12-month adjuvant treatment with lenvatinib can improve one-year recurrence-free survival rate (RFS) of HCC patients after surgical resection.

Detailed Description

There's no widely accepted adjuvant therapy for patients with HCC. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, was approved for advanced or unresectable HCC. In this study, investigators aim to evaluate the effects and safety of adjuvant apatinib therapy for the patients who underwent curative resection for HCC with high risk of disease recurrence.

Participants who underwent radical resection for HCC with high risk of tumor recurrence will be recruited in this study. During 4 to 6 weeks after surgery, each participant will receive a screening visit to exclude residual tumors. Each eligible participant will be treated with lenvatinib until tumor recurrence, intolerant adverse effect, participant' refusal, or completing 12-month treatment.

Study Timeline

• Study Start: 2019-12-12
• Status Verified: 2020-01
• Study First Submitted: 2020-01-05
• Study First Submitted QC: 2020-01-11
• Last Update Submitted: 2020-01-11
• Study First Posted: 2020-01-14
• Last Update Posted: 2020-01-14
• Primary Completion: 2021-12-30
• Study Completion: 2022-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Male or female patients aged 18-75;
2. Histological diagnosis of HCC;
3. Tumor stage before surgery: IIb/IIIa stage (>3 tumor nodules, or vascular invasion) HCC according to China Liver Cancer Staging System (or BCLC B/C/PVTT);
4. Underwent R0 resection (microscopic or macroscopic tumor clearance) in four to six weeks before recruitment; no residual tumor before recruitment by imaging study (MRI/CT), nor metastases to other organs;
5. Adequate liver, renal functions;
6. Written informed consent;
7. ECOG 0-1 and Child-Pugh A.

Exclusion Criteria

1. WBC<4.0*10^9/L, HB<80 g/L, and PLT<75*10^9/L at blood screening;
2. Coagulation function: (prothrombin time) international normalized ratio (INR) >2.3, or extension of prothrombin time>6 seconds;
3. Liver function: serum albumin (ALB)<2.8 g/dl, total bilirubin (TBIL)>51.3μmol/L, alanine aminotransferase and aspartate aminotransferase (ALT and AST)>5 times the upper limit of normal range;
4. Renal function: serum creatinine (Cr)>1.5 times the upper limit of normal range;
5. lymph node metastases;
6. The participant has uncontrolled ascites, hepatic encephalopathy, Gilbert's syndrome, and sclerosing cholangitis, etc.;
7. The participant was included in other clinical trials 30 days before the selection;
8. Other conditions that the investigators considered that not unsuitable for inclusion.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lenvatinib Arm	Lenvima 4 mg Oral Capsule	Experimental: Participants will be given lenvatinib (12 mg/d for body weight≥60kg, 8 mg/d for body weight \< 60kg) for 12 months until disease recurrence or intolerance AEs or death.

Primary Outcome Measures

Name	Time	Method
1-year RFS rate	1 year after LPI	1-year RFS rate is defined as the percentage of patients who do not experience tumor recurrence or death from any cause after 1-year treatment.

Secondary Outcome Measures

Name	Time	Method
Health-related quality of life	13 months	Health-related quality of life questionnaire measured by EORTC QLQ-HCC18.
Overall survival (OS)	3 years	The duration from the date of first dosage to the date of death from any cause.
Adverse events	13 months	An adverse event (AE) refers to any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, but which does not necessarily have a causal relationship with this treatment. Number and classification of participants with treatment-related adverse events as assessed by CTCAE v4.0 were recorded.
Serious adverse events(SAE)	13 months	A serious adverse event (SAE) refers to an event in clinical trials that requires inpatient hospitalization or causes prolongation of existing hospitalization, permanent disability, incapacity, threats to life or death, and birth defect, etc. Number and classification of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 were recorded.

Trial Locations

Locations (4)

180 Fenglin Road; 🇨🇳 Shanghai, China

West China Hospital; 🇨🇳 Chengdu, Sichuan, China

Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

Anhui Provincial Hospital; 🇨🇳 Hefei, Anhui, China