A Phase I/Ib Study of AZD9150 (ISIS-STAT3Rx) in Patients With Advanced/Metastatic Hepatocellular Carcinoma

Phase 1

Completed

Conditions: Hepatocellular Carcinoma Metastatic
Advanced Adult Hepatocellular Carcinoma

Interventions: Drug: AZD9150

Registration Number: NCT01839604

Lead Sponsor: AstraZeneca

Brief Summary: This is a phase I/Ib open-label, multicentre study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of AZD9150 in patients with advanced/metastatic hepatocellular carcinoma.

Detailed Description: A Phase I/Ib, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9150 in Patients with Advanced/Metastatic Hepatocellular Carcinoma.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 58

Inclusion Criteria

Aged at least 18 years. Patient from Japan and Taiwan aged at least 20 years
Histologically or cytologically confirmed HCC (with the exception of fibrolamellar carcinoma or mixed variants of HCC with fibrolamellar histology OR clinically diagnosed HCC for patients with difficulty in obtaining histological diagnosis)
Relapsed, refractory, intolerant or unlikely to benefit from sorafenib (for example due to comorbidity)
Metastatic or locally advanced meeting ANY of the criteria below:
HCC not suitable to receive local therapy
Disease recurred or was refractory to last therapy (local or systemic)
Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 8 weeks

Exclusion Criteria

More than 2 prior systemic treatments for HCC
Prior grade 3 hematologic toxicity related to treatment with a JAK or STAT3 inhibitor
Presence of hepatic encephalopathy within 4 weeks of 1st dose
Uncontrolled massive ascites
High likelihood of bleeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AZD9150	AZD9150	There are two parts, dose escalation phase (Part A) and dose expansion phase (Part B).

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities During Cycle 1	DLT assessment window - Cycle 1 (22 days)	Cycle 1 was defined as 3 loading doses given on Days 1, 3, and 5 followed by 3 weekly doses given on Days 8, 15, and 22.

Secondary Outcome Measures

Name	Time	Method
Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Cmax, Using the Plasma Concentration Data.	8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day1 of Cycle1.	8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. From the multiple samples a timecourse is obtained of treatment conc in the plasma over time. From this curve the associated PK parameters e.g. Cmax are obtained. For n patients we obtain up to n parameters which can then be averaged.
Preliminary Assessment of the Anti-tumour Activity of AZD9150 by Evaluation of Tumour Response.	Every 6 weeks, assessed up to 12 months.	Tumour response assessment by modified Response Evaluation Criteria in Solid Tumours (RECIST). Overall tumour response: assessed by mRECIST for HCC overall visit response of CR (disappearance of baseline TLs and NTLs), PR (\>=30% decrease in sum of TLs), SD (neither PR nor PD), PD (sum TLs increased \>20%), or NE .
Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Tmax, Using the Plasma Concentration Data.	8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day 1 of Cycle 1.	8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1.