Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma

• Status: Completed
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is an open-label, multi-center, phase 1, dose escalation study with a phase 2 expansion cohort to determine the safety, pharmacokinetics and preliminary anti-tumor activity of intravenous TKM-080301 in subjects with advanced hepatocellular carcinoma (HCC).

This study is being done to:

• Test the safety and tolerability of TKM-080301 in subjects with advanced hepatocellular carcinoma

• Find the highest dose of TKM-080301 that can be given without causing side effects, called the maximum tolerated dose (MTD).

• Provide a preliminary assessment of anti-tumor activity of TKM-080301

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Arbutus Biopharma Corporation

Criteria

Key Inclusion Criteria:

• Child-Pugh class of A

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5.0 × ULN

• Total bilirubin ≤3.0 mg/dL

• Platelets ≥75,000 /mL

• International Normalized Ratio (INR) ≤1.7

• Subjects must meet the protocol-defined criteria for both hepatitis B virus (HBV) and hepatitis C virus (HCV) status

Key Exclusion Criteria:

• History of significant cardiovascular disease will be excluded

• History of liver transplant.

• Diagnosis of fibrolamellar HCC or tumors of mixed histology.

• Subjects known to be positive for Human immunodeficiency virus (HIV) infection.

• Known central nervous system (CNS) or brain metastases.

• Poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently than once every 3 months.

• Symptomatic encephalopathy within 3 months prior to the first dose of TKM-080301 and/or requirement for medication for encephalopathy.

• Esophageal variceal bleeding within 2 weeks prior to the first dose of TKM-080301.

• Asthma or chronic obstructive pulmonary disease (COPD) requiring daily medication.

• Prior therapy with nitrosoureas or mitomycin within 6 weeks prior to the first dose of TKM-080301.

• Prior therapy with any biologic chemotherapeutic or investigational drug within 5 half-lives or 3 weeks, whichever is longer prior to the first dose of TKM 080301.