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.

Gastric Cancer Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01219543
• Other study ID #: D1060C00004
• Status: Terminated
• Phase: Phase 1
• First received: October 11, 2010
• Last updated: January 7, 2013
• Start date: November 2010
• Est. completion date: December 2012

Study information

• Verified date: January 2013
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 47
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

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 Solid Malignancies
• Carcinoma
• Carcinoma, Hepatocellular
• Child-Pugh A to B7 Advanced Hepatocellular Carcinoma
• EGFR and/or ROS Mutant NSCLC
• Gastric Cancer
• Lung Metastasis Carcinoma
• Lung Neoplasms
• Neoplasm Metastasis
• Neoplasms
• Solid Tumour
• Stomach Neoplasms

Intervention

Drug:
• AZD1480 Daily
Oral Dose, Capsule, Daily Dosing
• AZD1480 BID
Oral Dose, Capsule, BID Dosing

Locations

Country	Name	City	State
Korea, Republic of	Research Site	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To investigate the safety and tolerability of AZD1480		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	Yes
Secondary	To evaluate the pharmacokinetics (PK) of AZD1480 following single dose and multiple doses		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.	No
Secondary	To obtain a preliminary assessment of the anti-tumour activity of AZD1480		Tumour response assessment by RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1 every 6 weeks	No