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

Advanced Adult Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01839604
• Other study ID #: D5660C00001
• Secondary ID: ISIS 481464
• Status: Completed
• Phase: Phase 1
• First received: March 21, 2013
• Last updated: February 13, 2015
• Start date: May 2013
• Est. completion date: February 2015

Study information

• Verified date: February 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)South Korea: Institutional Review BoardJapan: Pharmaceuticals and Medical Devices AgencyJapan: Institutional Review BoardTaiwan: Institutional Review BoardTaiwan: Department of HealthHong Kong: Department of HealthHong Kong: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Adult Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma Metastatic

Intervention

Drug:
• AZD9150
Intravenous infusion over 3 hours.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Hong Kong,  Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	Assessed up to12 months	Yes
Secondary	Evaluation of pharmacokinetics (PK) of AZD9150 (following a single and multiple 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, 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.	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.	No
Secondary	Obtaining of a 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).	Every 6 weeks, assessed up to 12 months.	No
Secondary	Evaluation of pharmacokinetics (PK) of AZD9150 (following a single and multiple 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, 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.	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.	No