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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by AstraZeneca
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01839604
First received: March 21, 2013
Last updated: July 11, 2014
Last verified: July 2014
  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: Allocation: Non-Randomized
Endpoint Classification: Safety Study
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Investigation of the safety and tolerability of AZD9150 when given intravenously to patients with hepatocellular carcinoma and determine a recommended phase II dose and schedule (RP2D) by evaluating dose limiting toxicities occurred during cycle 1. [ Time Frame: Assessed up to12 months ] [ Designated as safety issue: Yes ]
    For routine safety monitoring, visit scheduled on Screening, Cycle1Day1, 3, 5, 8, 15 and 22, Day1, 8, 15 and 22 of every Cycle until study discontinuation and 28-day follow up,assessed up to 12 months.


Secondary Outcome Measures:
  • Evaluation of pharmacokinetics (PK) of AZD9150 (following a single and multiple administrations in patients with HCC by determining Cmax, using the plasma concentration data. [ Time Frame: 8 times of PK sampling on Day1 of Cycle1 and once on Day3,5,8,15 and 22 of Cycle1 and on Day1 of Cycle2-5. Additional 6 patients in Japan; 8 times of PK sampling on Day1 of Cycle1 and once on Day3,5,8 and 15 of Cycle1 and 9 times on Day22 of Cycle1. ] [ Designated as safety issue: No ]
    8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1, once (pre-dose) on Day 3, 5, 8, 15 and 22 of Cycle1 and Day1 of Cycle2-5. 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, once (pre-dose) on Day 3, 5, 8 and 15 of Cycle1 and 9 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24, 72 hours post-dose) on Day22 Cycle1.

  • Obtaining of a preliminary assessment of the anti-tumour activity of AZD9150 by evaluation of tumour response. [ Time Frame: Every 6 weeks, assessed up to 12 months. ] [ Designated as safety issue: No ]
    Tumour response assessment by modified Response Evaluation Criteria in Solid Tumours (RECIST).

  • Evaluation of pharmacokinetics (PK) of AZD9150 (following a single and multiple administrations in patients with HCC by determining Tmax, using the plasma concentration data. [ Time Frame: 8 times of PK sampling on Day1 of Cycle1 and once on Day3,5,8,15 and 22 of Cycle1 and on Day1 of Cycle2-5. Additional 6 patients in Japan; 8 times of PK sampling on Day 1 of Cycle 1 and once on Day3,5,8 and 15 of Cycle 1 and 9 times on Day 22 of cycle1. ] [ Designated as safety issue: No ]
    8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1, once (pre-dose) on Day 3, 5, 8, 15 and 22 of Cycle1 and Day1 of Cycle2-5 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, once (pre-dose) on Day 3, 5, 8 and 15 of Cycle1 and 9 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24, 72 hours post-dose) on Day22 Cycle1.


Estimated Enrollment: 56
Study Start Date: May 2013
Estimated Study Completion Date: February 2015
Estimated 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 and older
Genders Eligible for Study:   Both
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

Contacts
Contact: AstraZeneca Clinical Study Information 800-236-9933 ClinicalTrialTransparency@astrazeneca.com

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

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01839604     History of Changes
Other Study ID Numbers: D5660C00001, ISIS 481464
Study First Received: March 21, 2013
Last Updated: July 11, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)
South Korea: Institutional Review Board
Japan: Pharmaceuticals and Medical Devices Agency
Japan: Institutional Review Board
Taiwan: Institutional Review Board
Taiwan: Department of Health
Hong Kong: Department of Health
Hong Kong: Ethics Committee

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

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
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 July 28, 2014