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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cancer, Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: AZD8055


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD8055<br>Dose escalation | Drug: AZD8055<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | May not be reported in the CSR | Blood sample on Day 1 or at any other visit during study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mTor Kinase Inhibitor, Phase I/II, Dose escalation, Hepatocellular carcinoma (HCC), Asia, HCC, Safety and pharmacokinetics