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

January 13, 2017 updated by: AstraZeneca

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hongkong, Hong Kong
        • Research Site
  • Japan
      • Chuo-ku, Japan
        • Research Site
      • Kashiwa-shi, Japan
        • Research Site
      • Matsuyama-shi, Japan
        • Research Site
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Research Site
  • Taiwan
      • Tainan, Taiwan
        • Research Site
      • Taipei, Taiwan
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AZD9150
There are two parts, dose escalation phase (Part A) and dose expansion phase (Part B).
Drug: AZD9150
Intravenous infusion over 3 hours.
Other Names:
  • ISIS 481464

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose Limiting Toxicities During Cycle 1
Time Frame: 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.
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.
Time Frame: 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.
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.
Time Frame: 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 .
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.
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Collaborators

Ionis Pharmaceuticals, Inc.

Investigators

  • Study Director: Frank Neumann, MD, AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

March 21, 2013

First Submitted That Met QC Criteria

April 22, 2013

First Posted (Estimate)

April 25, 2013

Study Record Updates

Last Update Posted (Actual)

March 6, 2017

Last Update Submitted That Met QC Criteria

January 13, 2017

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D5660C00001
  • ISIS 481464 (Other Identifier: ISIS Pharmaceuticals Inc)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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