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

Primary Purpose

Advanced Adult Hepatocellular Carcinoma, Hepatocellular Carcinoma Metastatic

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AZD9150
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Adult Hepatocellular Carcinoma focused on measuring Child-Pugh A to B7,, Advanced/Metastatic Hepatocellular Carcinoma,, AZD9150,, Antisense Oligonucleotide Inhibitor of STAT3

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AZD9150

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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 .
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.

Full Information

First Posted
March 21, 2013
Last Updated
January 13, 2017
Sponsor
AstraZeneca
Collaborators
Ionis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01839604
Brief Title
A Phase I/Ib Study of AZD9150 (ISIS-STAT3Rx) in Patients With Advanced/Metastatic Hepatocellular Carcinoma
Official Title
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

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Ionis Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Adult Hepatocellular Carcinoma, Hepatocellular Carcinoma Metastatic
Keywords
Child-Pugh A to B7,, Advanced/Metastatic Hepatocellular Carcinoma,, AZD9150,, Antisense Oligonucleotide Inhibitor of STAT3

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AZD9150
Arm Type
Experimental
Arm Description
There are two parts, dose escalation phase (Part A) and dose expansion phase (Part B).
Intervention Type
Drug
Intervention Name(s)
AZD9150
Other Intervention Name(s)
ISIS 481464
Intervention Description
Intravenous infusion over 3 hours.
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities During Cycle 1
Description
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.
Time Frame
DLT assessment window - Cycle 1 (22 days)
Secondary Outcome Measure Information:
Title
Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Cmax, Using the Plasma Concentration Data.
Description
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.
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.
Title
Preliminary Assessment of the Anti-tumour Activity of AZD9150 by Evaluation of Tumour Response.
Description
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 .
Time Frame
Every 6 weeks, assessed up to 12 months.
Title
Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Tmax, Using the Plasma Concentration Data.
Description
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.
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Neumann, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Hongkong
Country
Hong Kong
Facility Name
Research Site
City
Chuo-ku
Country
Japan
Facility Name
Research Site
City
Kashiwa-shi
Country
Japan
Facility Name
Research Site
City
Matsuyama-shi
Country
Japan
Facility Name
Research Site
City
Seoul
Country
Korea, Republic of
Facility Name
Research Site
City
Tainan
Country
Taiwan
Facility Name
Research Site
City
Taipei
Country
Taiwan

12. IPD Sharing Statement

Learn more about this trial

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

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