Study of Axitinib in Patients With Unresectable Hepatocellular Carcinoma (AXITINIB)

A Phase II Trial of Axitinib (AG-013736) After Prior Antiangiogenic Therapy in Advanced Hepatocellular Carcinoma

The purpose of this study is to evaluate the potential role of Axitinib (AG-013736) in the treatment of unresectable/metastatic hepatocellular carcinoma (HCC)

Study Overview

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

Detailed Description

This is a phase II study of an investigational drug, Axitinib following prior antiangiogenic therapy in patients with advanced hepatocellular carcinoma. Hepatocellular carcinoma (HCC) is a primary cancer of the liver. Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. A tyrosine kinase is an enzyme that can inhibit angiogenesis. In this study, patients with advanced HCC who have failed prior antiangiogenic therapy, will receive Axitinib in cycles of 4 weeks. Axitinib is an oral, potent and selective inhibitor of angiogenesis. This study will evaluate the response rate of HCC following treatment with Axitinib as well as safety, feasibility, overall survival of patients, progression-free survival, and quality of life in persons with unresectable HCC. The study also compares response determined by RECIST to response determined by Choi Criteria.

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

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Foothills Hospital, Alberta Health Services
  • Ontario
    • Toronto, Ontario, Canada
      • University Health Network, Princess Margaret 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:

• Unresectable and/or metastatic Hepatocellular Carcinoma
• Previous treatment with tyrosine kinase inhibitors or antiangiogenic drugs
• Life expectancy of ≥12 weeks
• At least one tumor lesion
• At least 2 weeks since the end of prior systemic treatment
• No evidence of pre-existing uncontrolled hypertension
• ECOG 0 or 1
• Adequate organ function
• Not appropriate for curative therapy
• Child A or B7 cirrhosis
• CLIP score ≤ 4

Exclusion Criteria:

• Received any other systemic therapy for Hepatocellular Carcinoma within 2 weeks prior to treatment
• Major surgery <4 weeks or radiation therapy <2 weeks of starting the study treatment
• Previous or concurrent cancer that is distinct in primary site or histology from Hepatocellular Carcinoma
• Severe acute or chronic medical or psychiatric condition
• Need for treatment with prohibited drugs
• Has received local therapy to all measurable lesions
• Stage B8 or higher liver cirrhosis
• Ascites refractory to diuretic therapy
• Clinically significant ECG abnormality

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; Oral Axitinib (5mg, twice daily) will be administered to all patients	Drug: Axitinib (AG-013736); 5mg, oral, twice daily, continuous dosing. A dosing cycle is defined as 4 weeks. Treatment may continue until disease progression/relapse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate	Response rate assessed by CT scan at 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility	The ability to administer one or more cycles of Axitinib to >70% of patients at a dose of 5mg po BID	Assessed at the end of stage 1 (10 patients accrued) and at the end of trial (Stage 2, 29 patients total)
Overall survival		At the completion of trial, 1.5 years
Response rate comparison		Comparison of outcomes with RECIST criteria to Choi criteria and changes to perfusion on DCE ultrasound will occur at the end of stage 1 (after accrual of 10 patients) and trial completion
Progression-free survival		At trial completion, 1.5 years
Quality of life	Assessed by FACT-Hep	At completion of trial, 1.5 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Efficacy and Toxicity in Asian vs non-Asian patients will be assessed by comparing the adverse effects profile and rate of grade 3 and grade 4 toxicity in these populations	At completion of trial, 1.5 years
Number of Participants with Adverse Events as a Measure of Safety	Adverse effects profile and rate of grade 3 and 4 toxicity will be assessed as a measure of safety	At completion of trial, 1.5 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Pfizer
• Investigators: Principal Investigator: Jennifer Knox, MSc, FRCPC, MD, University Health Network, Princess Margaret Hospital; Principal Investigator: Kelly Burak, MD, FRCPC, BSc, MSc, University of Calgary

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: February 14, 2011
• First Submitted That Met QC Criteria: April 11, 2011
• First Posted (Estimate): April 12, 2011

Study Record Updates

• Last Update Posted (Actual): December 12, 2019
• Last Update Submitted That Met QC Criteria: December 11, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Liver Cancer; Advanced Hepatocellular Carcinoma; Axitinib; AG-013736
• 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: WS515376