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.

Study Overview
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Brief Summary
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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.

Official Title
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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.

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

Intervention / Treatment
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* Drug: AZD1480 Daily
* Drug: AZD1480 BID


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>Daily dosing of AZD1480 to the patients with solid tumours excluding HCC | Drug: AZD1480 Daily<br>* Oral Dose, Capsule, Daily Dosing<br>|
| Experimental: Part B<br>BID dosing of AZD1480 to the patients with advanced HCC (Child-Pugh A to B7) | Drug: AZD1480 BID<br>* Oral Dose, Capsule, BID Dosing<br>|
| Experimental: Part C<br>BID dosing of AZD1480 to the patients with solid tumours excluding HCC | Drug: AZD1480 BID<br>* Oral Dose, Capsule, BID Dosing<br>|
| Experimental: Expansion<br>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<br>* Oral Dose, Capsule, BID Dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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