Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of Tor Kinase Inhibitor in Liver Cancer Patients

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT00999882

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

8.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of the study is to establish a safe dose of AZD8055 in patients with mild or moderate liver disease by providing information on any potential side effects this drug may cause and collecting data about how hepatocellular carcinoma responds to the drug.

Condition or Disease	Intervention/Treatment	Phase
Cancer Advanced Hepatocellular Carcinoma	Drug: AZD8055	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Tor Kinase Inhibitor (AZD8055) in Asian Patients With Advanced Stage Hepatocellular Carcinoma (HCC) and With Mild or Moderate Hepatic Impairment

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD8055 Dose escalation	Drug: AZD8055 Dose escalation phase: Tablet taken orally, a single dose of AZD8055 on Day 1, followed by twice daily continuous dosing from Day 3 onwards, till discontinuation or withdrawal.Expansion phase: twice daily continuous dosing from Day 1 onwards till discontinuation or withdrawal.

Arm

Intervention/Treatment

Experimental: AZD8055

Dose escalation

Drug: AZD8055

Dose escalation phase: Tablet taken orally, a single dose of AZD8055 on Day 1, followed by twice daily continuous dosing from Day 3 onwards, till discontinuation or withdrawal.Expansion phase: twice daily continuous dosing from Day 1 onwards till discontinuation or withdrawal.

Outcome Measures

Primary Outcome Measures

Safety and tolerability (Adverse events, vital signs, ECG, chemistry, haematology, urinalysis, physical examination) [Every week for Cycle 1 and 2, every 2 weeks from cycle 3 onwards, every 4 weeks from cycle 7 onwards]
Evaluate the pharmacokinetics of AZD8055 following both single and multiple dosing [Blood samples on 6 occasions during the first Cycle of the study (28 days)]

Secondary Outcome Measures

To make a preliminary assessment of efficacy [Every 4 weeks]
To investigate the possible relationship between plasma concentration of AZD8055 concentrations and the extent of liver impairment. [During Cycle 1 of the study - blood samples before study treatment and then on Day 1, 3, 10, 17, 24, 30 and then on day 1 of every cycle]
Evaluate the change in Phosphorylation levels of certain biomarkers before and after treatment with AZD8055 [Blood samples x 3 times on Day 1 of the first cycle]
To collect and store DNA for future exploratory research that may influence response to AZD8055 [Blood sample on Day 1 or at any other visit during study]
May not be reported in the CSR

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Advanced stage Hepatocellular Carcinoma (HCC) confirmed by cytology or histology
Advanced stage Hepatocellular Carcinoma (HCC) or metastatic Hepatocellular Carcinoma (HCC) which is inoperable and incurable with standard available treatments
Relatively good overall health other than cancer (WHO performance status (0-2)

Exclusion Criteria:

Patients with severe heart conditions, or those who have had heart surgery such as coronary artery bypass graft within the last 6 months, or patients with uncontrolled high blood pressure despite medical management.
Patients must not have received any other anti cancer therapy including TACE within 21 days of entering the trial
Patients must not have received a liver transplant.