Clinical trial NCT01219543: A Phase I Study of AZD1480 in Patients With Advanced Solid Malignancies and Advanced Hepatocellular Carcinoma in the Escalation Phase,Non-Small Cell Lung Cancer(NSCLC) and Non-smokers With Lung Metastasis and Gastric Cancer and Solid Tumour in the Expansion Phase.
Official title: A Phase I, Open-label, Multicentre, Dose Escalation Study to Assess the Safety and Tolerability, and Pharmacokinetics of AZD1480 in Asian Patients With Advanced Solid Malignancies and Asian Patients With Child-Pugh A to B7 Advanced Hepatocellular Carcinoma (HCC) in the Escalation Phase, Estimated Glomerular Filtration Rate(EGFR) or ROS Mutant NSCLC and Non-smokers With Lung Metastasis and Gastric Cancer and Solid Tumour With Biopsy Available in the Expansion Phase.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumour
Advanced Solid Malignancies
Child-Pugh A to B7 Advanced Hepatocellular Carcinoma
EGFR and/or ROS Mutant NSCLC
Lung Metastasis Carcinoma
Gastric Cancer
Keywords: Advanced solid malignancies
Child-Pugh A to B7 advanced hepatocellular carcinoma
EGFR and/or ROS mutant NSCLC
Non-smokers with lung metastasis
Gastric cancer
Solid tumour
AZD1480
JAK1/JAK2 kinase inhibitor
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-10-13
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is Phase I, open-label and dose escalation study to evaluate the safety and tolerability of AZD1480(JAK2 inhibitor) in Asian patients with advanced solid tumors (Part A and C) and in patients with advanced HCC (Part B) in the escalation phase, EGFR or ROS mutant NSCLC and non-smokers with lung metastasis and gastric cancer in the expansion phase and to evaluate daily and BID dosing.


Eligibility criteria: Inclusion Criteria:

* Male or female aged 18 years or older
* For Part A and C: Histological or cytological confirmation of a solid malignant tumour refractory to standard therapies or for which no standard therapies exist. Patients with lymphoma \& HCC are excluded.
* For Expansion : Histological or cytological confirmation of
* Expansion 1: EGFR and/or ROS mutant NSCLC or Non-smokers with lung metastasis
* Expansion 2: Gastric cancer or solid tumour with biopsy available (consenting paired biopsies)refractory to standard therapies or for which no standard therapies exist. Patients with lymphoma \& HCC are excluded.
* For Part B : Advanced or metastatic HCC, unresectable and incurable with ablative therapy or TACE, with no standard therapy available.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks
* For Part B : Child-Pugh liver function status classified as A to B7

Exclusion Criteria:

* For any other chemotherapy, immunotherapy or anticancer agents, within 5 half lives or 3 weeks must have elapsed from treatment to of the first dose of investigational product, whichever is shorter.
* With the exception of alopecia, any unresolved toxicities from prior therapy ≥ Grade 2 of CTCAE V4.02 at the time of starting study (except LFTs for HCC patients, which may be Grade 2 at the time of starting the study)
* Any of the following conditions:Interferon treatment for HBV and HCV Prior Liver Transplantation
* Inadequate bone marrow reserve or organ function as demonstrated by laboratory values
* Evidence of established interstitial lung disease(ILD) on baseline high resolution computerized tomography(HRCT)

Primary outcomes:
measure: To investigate the safety and tolerability of AZD1480
timeFrame: Safety and tolerability monitoring will proceed for whole study period. Screening, Cycle1Day1, Cycle1Day5 (only for Part B), Cycle1Day8, Cycle1Day15, Cycle2Day1, Cycle2Day8 and Day1 of further Cycles, IP discontinued visit and 30-days follow up
Secondary outcomes:
measure: To evaluate the pharmacokinetics (PK) of AZD1480 following single dose and multiple doses
timeFrame: Part A and Expansion - 12 times during Cycle 1, 11 times during Cycle 2. Part B and C - 11 times during Cycle 1, 10 times during Cycle 2. *1 additional PK sample in Cycle 1 will be collect for optional biopsy sample collected patients.
measure: To obtain a preliminary assessment of the anti-tumour activity of AZD1480
timeFrame: Tumour response assessment by RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1 every 6 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Becker Hewes, MD
role: STUDY_DIRECTOR
affiliation: Asian Medical Center
name: Kang Yoon-Koo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: