Anlotinib Combined With TACE in Hepatocellular Carcinoma Patients at High Risk of Post Surgery Recurrence (ALTER-H-004)

An Open, Single Arm,Multicenter Clinical Trial of Anlotinib Combined With Transcatheter Arterial Chemoembolization for Adjuvant Therapy in Patients With High Risk of Recurrence After Resection of Advanced Hepatocellular Carcinoma

A single-arm, open-label clinical trial to assess the effects and safety of anlotinib hydrochloride combined with transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma(HCC) patients at high risk of post surgery recurrence.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma; Anlotinib; TACE
• Intervention / Treatment: Drug: Anlotinib Hydrochloride; Procedure: TACE

Detailed Description

Hepatocellular carcinoma is one of the most common malignant tumors in the world with high incidence and mortality. Recurrence of HCC is still a great challenge and threat to the patients after resection surgery. Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.

HCC patients who meet the eligibility criteria of this clinical trial will adopt postoperative TACE combined with anlotinib hydrochloride. At Day4 of TACE,anlotinib 12mg QD PO d1-14, 21 days per cycle until disease progresses or intolerant.

Primary Efficacy Endpoint: Disease free survival (DFS);Secondary Efficacy Endpoints: 1-year DFS Rate and Time to recurrence (TTR)(According to RECIST Version 1.1).Safety will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
  • Shaanxi
    • Hanzhong, Shaanxi, China, 723000
      • Hanzhong Central Hospital
    • Xi'an, Shaanxi, China, 710000
      • The First Affiliated Hospital of Xi'an Jiaotong University
    • Xi'an, Shaanxi, China, 710000
      • Tangdu hospital of the Fourth Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients participate in the study voluntarily and sign informed consent with good compliance.
• After hepatectomy, satisfy any of the following recurrence factors was assessed:≥5 cm and < 10 cm of tumor diameter; tumor number≥3; tumor microvascular invasion grade M1; portal vein carcinoma thrombus resection(Ⅰ、Ⅱ).
• Histological or cytological confirmation of hepatocellular carcinoma, or at least two imaging tests with hepatocellular carcinoma characteristics, or one imaging test with hepatocellular carcinoma characteristics and AFP > 400μg/L.
• TACE treatment (cTACE only) was completed within 1-2 months after hepatectomy.
• ≥ 18 and ≤ 75 years of age.
• ECOG performance status of 0-1.
• liver function child-Pugh class A or B (≤7 points).
• Except for hepatectomy, no previous tumor-related treatment was received, and the remaining liver was assessed to have good liver function.

Exclusion Criteria:

• Patients who have had or are currently complicated with other malignant tumors,or recurrent hepatocellular carcinoma (>10 mm)in baseline data or in TACE.
• Patients with absolute contraindications to TACE.
• Patients with HCV infection.
• Urine protein ≥ ++，and 24-hour urinary protein excretion>1.0 g confirmed.
• Pregnant or lactating women.
• Patients with mental illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Administration anlotinib and it should be continued until relapse of HCC or intolerable toxicity or patients withdrawal of consent.	Drug: Anlotinib Hydrochloride; Anlotinib 12mg QD PO d1-14, 21 days per cycle.; Procedure: TACE; TACE first, followed by anlotinib within day4（+/-1days）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	The period from resection surgery to recurrence of HCC	From randomization to recurrence of HCC or death (up to 1year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year DFS Rate	One year ratio of DFS	From randomization to recurrence of HCC or death (up to 1year)
Time to recurrence	The period from resection surgery to recurrence of HCC	From randomization to recurrence of HCC(up to 1year)
Incidence of Treatment-Emergent Adverse Events Safety and Tolerability	Any adverse effects occur during the use of anlotinib	Up to 30 day safety follow-up visit

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborators: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Investigators: Study Chair: Zheng Wu, PhD, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: December 25, 2019
• First Submitted That Met QC Criteria: December 25, 2019
• First Posted (Actual): December 30, 2019

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Recurrence
• Other Study ID Numbers: KYLLSL-2019-185

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No