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.

This study has been terminated.
(Compound development discontinued)
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01219543
First received: October 11, 2010
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Solid Tumour
Advanced Solid Malignancies
Child-Pugh A to B7 Advanced Hepatocellular Carcinoma
EGFR and/or ROS Mutant NSCLC
Lung Metastasis Carcinoma
Gastric Cancer
Drug: AZD1480 Daily
Drug: AZD1480 BID
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, 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.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: November 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A
Daily dosing of AZD1480 to the patients with solid tumours excluding HCC
Drug: AZD1480 Daily
Oral Dose, Capsule, Daily Dosing
Experimental: Part B
BID dosing of AZD1480 to the patients with advanced HCC (Child-Pugh A to B7)
Drug: AZD1480 BID
Oral Dose, Capsule, BID Dosing
Experimental: Part C
BID dosing of AZD1480 to the patients with solid tumours excluding HCC
Drug: AZD1480 BID
Oral Dose, Capsule, BID Dosing
Experimental: Expansion
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.
Drug: AZD1480 BID
Oral Dose, Capsule, BID Dosing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  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: NCT01219543

Locations
Korea, Republic of
Research Site
Seoul, Korea, Republic of
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Becker Hewes, MD AstraZeneca
Principal Investigator: Kang Yoon-Koo, MD, PhD Asian Medical Center
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01219543     History of Changes
Other Study ID Numbers: D1060C00004
Study First Received: October 11, 2010
Last Updated: January 7, 2013
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)
South Korea: Institutional Review Board

Keywords provided by AstraZeneca:
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

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Stomach Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Lung Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Neoplastic Processes
Pathologic Processes
Adenocarcinoma
Liver Neoplasms
Liver Diseases

ClinicalTrials.gov processed this record on August 21, 2014