Back to resultsA 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.
Primary Purpose
Solid Tumour, Advanced Solid Malignancies, Child-Pugh A to B7 Advanced Hepatocellular Carcinoma
Status
Terminated
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
AZD1480 Daily
AZD1480 BID
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumour focused on measuring 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
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)
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A
Part B
Part C
Expansion
Arm Description
Daily dosing of AZD1480 to the patients with solid tumours excluding HCC
BID dosing of AZD1480 to the patients with advanced HCC (Child-Pugh A to B7)
BID dosing of AZD1480 to the patients with solid tumours excluding HCC
BID dosing of AZD1480 to the patients with EGFR or ROS mutant NSCLC and non-smokers with lung metastasis and gastric cancer and solid tumour with biopsy available.
Outcomes
Primary Outcome Measures
To investigate the safety and tolerability of AZD1480
Secondary Outcome Measures
To evaluate the pharmacokinetics (PK) of AZD1480 following single dose and multiple doses
To obtain a preliminary assessment of the anti-tumour activity of AZD1480
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01219543
Brief Title
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
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Terminated
Why Stopped
Compound development discontinued
Study Start Date
November 2010 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A
Arm Type
Experimental
Arm Description
Daily dosing of AZD1480 to the patients with solid tumours excluding HCC
Arm Title
Part B
Arm Type
Experimental
Arm Description
BID dosing of AZD1480 to the patients with advanced HCC (Child-Pugh A to B7)
Arm Title
Part C
Arm Type
Experimental
Arm Description
BID dosing of AZD1480 to the patients with solid tumours excluding HCC
Arm Title
Expansion
Arm Type
Experimental
Arm Description
BID dosing of AZD1480 to the patients with EGFR or ROS mutant NSCLC and non-smokers with lung metastasis and gastric cancer and solid tumour with biopsy available.
Intervention Type
Drug
Intervention Name(s)
AZD1480 Daily
Intervention Description
Oral Dose, Capsule, Daily Dosing
Intervention Type
Drug
Intervention Name(s)
AZD1480 BID
Intervention Description
Oral Dose, Capsule, BID Dosing
Primary Outcome Measure Information:
Title
To investigate the safety and tolerability of AZD1480
Time Frame
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 Outcome Measure Information:
Title
To evaluate the pharmacokinetics (PK) of AZD1480 following single dose and multiple doses
Time Frame
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.
Title
To obtain a preliminary assessment of the anti-tumour activity of AZD1480
Time Frame
Tumour response assessment by RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1 every 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Becker Hewes, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Kang Yoon-Koo, MD, PhD
Organizational Affiliation
Asian Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
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.
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