Axitinib as Second-line Treatment for Advanced Hepatocellular Carcinoma

This is a phase II study of axitinib as the second-line on the treatment of advanced hepatocellular carcinoma (HCC).

The purpose of this study is a proof-of-concept study to see if axitinib has any anti-tumor effect in HCC. The primary endpoint is disease stabilization that lasts for at least 8 weeks without progression of tumor-related symptoms.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: AG-013736

Detailed Description

Axitinib can can inhibit the activity of multiple angiogenesis-related signaling pathways. Promising anti-tumor activity has been demonstrated in patients with renal cell carcinoma, thyroid cancer, and melanoma. The potent anti-angiogenic activity of axitinib makes it a promising agent for the treatment of HCC.

This is a single-arm, open-label phase II trial. Eligible patients will receive axitinib, starting at 5 mg orally twice daily in the fasting status, until objective disease progression, development of unacceptable toxicity, or voluntary discontinuation. Dose titration will be done according to the severity of adverse events.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei City, Taiwan, 114
    • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically diagnosed HCC, OR clinically diagnosed HCC
• Inoperable tumor(s) and no applicable curative therapy. Not amenable to loco-regional therapy
• Documented progression with or intolerance to sorafenib treatment as first- line therapy for advanced HCC
• At least one measurable tumor, according to RECIST version 1.1, that has not been treated with any local procedure
• ECOG performance status 0 or 1
• Life expectancy is at least 2 months
• Child-Pugh class A liver function.

Exclusion Criteria:

• Systemic therapy other than sorafenib as first-line therapy for advanced HCC
• History of HCC tumor rupture
• Presence of brain or leptomeningeal metastases
• Esophageal/gastric varices or active peptic ulcers that are considered to have high risk of bleeding
• History of upper gastrointestinal bleeding within 1 year
• Major systemic diseases that the investigator considers inappropriate for participation
• Uncontrollable hypertension
• Proteinuria
• Current use or anticipated need for treatment with potent CYP3A4 inhibitor, CYP3A4 or CYP1A2 inducers
• Requirement of anticoagulant therapy with oral vitamin K antagonists
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation and in the judgment of the investigator would make the patient inappropriate for entry into this study

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: Axitinib	Drug: AG-013736; All enrolled patients will receive axitinib, 5 mg orally twice daily with food, until objective disease progression, development of unacceptable toxicity, or voluntary discontinuation by the subjects.; Other Names: Axitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
disease stabilization	8 weeks until tumor progression

Secondary Outcome Measures

Outcome Measure	Time Frame
time-to-tumor progression	8 weeks until tumor progression

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Taipei Veterans General Hospital, Taiwan; Tri-Service General Hospital
• Investigators: Principal Investigator: Ann-Lii Cheng, MD, PhD, Director/Professor

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 6, 2011
• First Submitted That Met QC Criteria: January 6, 2011
• First Posted (Estimate): January 10, 2011

Study Record Updates

• Last Update Posted (Estimate): February 9, 2017
• Last Update Submitted That Met QC Criteria: February 7, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: HCC
• 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; Axitinib
• Other Study ID Numbers: 201008013M