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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Adult Hepatocellular Carcinoma, Hepatocellular Carcinoma Metastatic

Intervention / Treatment
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* Drug: AZD9150


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD9150<br>There are two parts, dose escalation phase (Part A) and dose expansion phase (Part B). | Drug: AZD9150<br>* Intravenous infusion over 3 hours.<br>* Other names: ISIS 481464;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities During Cycle 1 | 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. | DLT assessment window - Cycle 1 (22 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Cmax, Using the Plasma Concentration Data. | 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. | 8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day1 of Cycle1. | 
| Preliminary Assessment of the Anti-tumour Activity of AZD9150 by Evaluation of Tumour Response. | 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 . | Every 6 weeks, assessed up to 12 months. | 
| Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Tmax, Using the Plasma Concentration Data. | 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AZD9150,, Antisense Oligonucleotide Inhibitor of STAT3, Child-Pugh A to B7,, Advanced/Metastatic Hepatocellular Carcinoma,