Clinical trial NCT01839604: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Adult Hepatocellular Carcinoma
Hepatocellular Carcinoma Metastatic
Keywords: Child-Pugh A to B7,
Advanced/Metastatic Hepatocellular Carcinoma,
AZD9150,
Antisense Oligonucleotide Inhibitor of STAT3
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2013-04-25
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities During Cycle 1
timeFrame: DLT assessment window - Cycle 1 (22 days)
Secondary outcomes:
measure: Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Cmax, Using the Plasma Concentration Data.
timeFrame: 8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day1 of Cycle1.
measure: Preliminary Assessment of the Anti-tumour Activity of AZD9150 by Evaluation of Tumour Response.
timeFrame: Every 6 weeks, assessed up to 12 months.
measure: Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Tmax, Using the Plasma Concentration Data.
timeFrame: 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.
Other outcomes:
Locations:
city: Hongkong
country: Hong Kong
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa-shi
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Frank Neumann, MD
role: STUDY_DIRECTOR
References: