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

This study has been completed.
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01839604
First received: March 21, 2013
Last updated: January 13, 2017
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Advanced Adult Hepatocellular Carcinoma
Hepatocellular Carcinoma Metastatic
Drug: AZD9150
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.

  • 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 .

  • 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.


Enrollment: 58
Study Start Date: May 2013
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: ISIS 481464

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.
  Eligibility

Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01839604

Locations
Hong Kong
Research Site
Hongkong, Hong Kong
Japan
Research Site
Chuo-ku, Japan
Research Site
Kashiwa-shi, Japan
Research Site
Matsuyama-shi, Japan
Korea, Republic of
Research Site
Seoul, Korea, Republic of
Taiwan
Research Site
Tainan, Taiwan
Research Site
Taipei, Taiwan
Sponsors and Collaborators
AstraZeneca
Ionis Pharmaceuticals, Inc.
Investigators
Study Director: Frank Neumann, MD AstraZeneca
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01839604     History of Changes
Other Study ID Numbers: D5660C00001
ISIS 481464 ( Other Identifier: ISIS Pharmaceuticals Inc )
Study First Received: March 21, 2013
Results First Received: February 1, 2016
Last Updated: January 13, 2017

Keywords provided by AstraZeneca:
Child-Pugh A to B7,
Advanced/Metastatic Hepatocellular Carcinoma,
AZD9150,
Antisense Oligonucleotide Inhibitor of STAT3

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on April 26, 2017