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

Phase 1

Terminated

Conditions: Cancer
Advanced Solid Malignancies

Interventions: Drug: AZD4547

Registration Number: NCT00979134

Lead Sponsor: AstraZeneca

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 95

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part B	AZD4547	Dose expansion phase, at the RD defined in Part A
Part C	AZD4547	Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A
Part A	AZD4547	Ascending doses of AZD4547 administered orally to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD)

Primary Outcome Measures

Name	Time	Method
Number of Participants With at Least 1 AE of CTCAE >=G3	Ongoing up to discontinuation up to 30 day FU.	To investigate the safety and tolerability of AZD4547
Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3	Ongoing up to discontinuation up to 30 day FU.	To investigate the safety and tolerability of AZD4547
Number of Patients Who Experienced at Least 1 AE	AEs are monitored from screenng through to 30 day follow up period	To investigate the safety and tolerability of AZD4547. System organ class (SOC), preferred term (PT), duration and severity all recorded.
Number of Participants Who Experienced at Least 1 Causally Related AE.	AEs are continually assessed from screening up to 30 day FU period	To investigate the safety and tolerability of AZD4547. A causally related AE is an AE deemed to be causally related to AZD4547.
Number of Participants Who Experienced at Least One SAE	Serious Adverse Events (SAEs) are continually assessed from Screening up to the end of the 30 day FU period.	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.
Number of Participants With at Least 1 Causally Related SAE	SAEs are continually monitored from screening to end of 30 FU period	To investigate the safety and tolerability of AZD4547: SAEs are assessed and deemed as causally related or not to AZD4547

Secondary Outcome Measures

Name	Time	Method
Css,Max (ng/mL)	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.	To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR)	Baseline assessment, then assessment every 6 weeks after start of treatment until objective disease progression.	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
AUC(0-infinity)	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.	To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
Cmax (ng/mL)	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.	To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
AUC,ss(0-infinity)	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.	To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.