Study is Designed to Assess the Safety and Tolerability of AZD4547 at Increasing Doses in Patients With Advanced Tumours

Study Overview
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Brief Summary
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This study is primarily designed to assess the safety and tolerability of AZD4547 at increasing doses in patients with advanced solid malignancies and for whom no standard medication options are available. It also assesses the blood levels and action of AZD4547 in the body over a period of time.

Official Title
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A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD4547 in Patients With Advanced Solid Malignancies

Conditions
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Cancer, Advanced Solid Malignancies

Intervention / Treatment
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* Drug: AZD4547
* Drug: AZD4547
* Drug: AZD4547


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum life expectancy of 12 weeks The presence of a solid, malignant tumour that is resistance to standard therapies or for which no standard therapies exist In the expansion for the study patients must have a tumour at least 1cm in size that can be measure using a CT or MRI scan, and provide a tumour sample to the sponsor company for testing of FGFR1 and/or 2 amplification Expansion, 5 groups of advanced cancer Solid tumours,FGFR1 and/or FGFR2 gene amplified Squamous NSCLC, FGFR1 gene low & high amplified Gastric adenocarcinoma, including the lower oesophagus/gastro-oesophageal junction, FGFR2 gene low & high amplified Aged at least 25 years Exclusion Criteria: Treatment with any other chemotherapy, immunotherapy or anticancer agents within 3 weeks before the first dose of study An inability to be able to take the study medication A bad reaction to AZD4547 or any drugs similar to it in structure or class.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 149 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>Ascending doses of AZD4547 administered orally to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD) | Drug: AZD4547<br>* Single dose is followed by washout 5-10 days before multiple dose<br>|
| Experimental: Part B<br>Dose expansion phase, at the RD defined in Part A | Drug: AZD4547<br>* Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily<br>|
| Experimental: Part C<br>Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A | Drug: AZD4547<br>* Patients start at a dose of 80 mg twice daily, with no washout<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Experienced at Least 1 AE | To investigate the safety and tolerability of AZD4547. System organ class (SOC), preferred term (PT), duration and severity all recorded. | AEs are monitored from screenng through to 30 day follow up period | 
| Number of Participants Who Experienced at Least 1 Causally Related AE. | To investigate the safety and tolerability of AZD4547. A causally related AE is an AE deemed to be causally related to AZD4547. | AEs are continually assessed from screening up to 30 day FU period | 
| Number of Participants With at Least 1 AE of CTCAE >=G3 | To investigate the safety and tolerability of AZD4547 | Ongoing up to discontinuation up to 30 day FU. | 
| Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3 | To investigate the safety and tolerability of AZD4547 | Ongoing up to discontinuation up to 30 day FU. | 
| Number of Participants Who Experienced at Least One SAE | To investigate the safety and tolerability of AZD4547. A SAE (Serious Adverse Event) is and AE (adverse Event) which fulfills one of the following criteria that the PI assesses closely such as results in death, immediately life-threatening, requires hospitalisation or prolongation of, results in significant disability, results in birth defect, may jepardise the patient or require intervention to prevent any of the previous outcomes. | Serious Adverse Events (SAEs) are continually assessed from Screening up to the end of the 30 day FU period. | 
| Number of Participants With at Least 1 Causally Related SAE | To investigate the safety and tolerability of AZD4547: SAEs are assessed and deemed as causally related or not to AZD4547 | SAEs are continually monitored from screening to end of 30 FU period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-infinity) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK samples out to 96 hours 0 to 96 hours post-dose after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. | 
| Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR) | To obtain a preliminary assessment of the anti tumour activity of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1. Objective response = CR + PR; CR=disappearance of all target lesions and PR is >=30% reduction in sum of longest diameter of target lesions | Baseline assessment, then assessment every 6 weeks after start of treatment until objective disease progression. | 
| Cmax (ng/mL) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK samples out to 96 hours 0-96 hours post dose after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. | 
| Css,Max (ng/mL) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK samples out to 96 hours 0-96 hours post-dose after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. | 
| AUC,ss(0-infinity) | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. | PK samples out to 96 hours 0-96 hours post dose after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Tumour, Advanced Solid Malignancies, FGFR, Squamous NSCLC, Gastric adenocarcinoma