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

Tracking Information
First Submitted Date ICMJE	September 16, 2009
First Posted Date ICMJE	September 17, 2009
Last Update Posted Date	June 26, 2015
Study Start Date ICMJE	October 2009
Actual Primary Completion Date	February 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 3, 2011)	To investigate the safety and tolerability of AZD4547 when given orally to patients with advanced solid malignancies and define the maximum tolerated dose (MTD) and/or a continuous, tolerable dose Recommended Dose (RD). [ Time Frame: Blood samples weekly during dosing. Physical Exam every 3 weeks. ECG & vital, minimum every 3 weeks. Ophthalmology at baseline, monthly for 3 months then every 8 weeks. MUGA/Echocardiogram at baseline, 3 weeks after start of dosing and every 3 months. ]
Original Primary Outcome Measures ICMJE; (submitted: September 16, 2009)	To investigate the safety and tolerability of AZD4547 when given orally to patients with advanced solid malignancies and define the maximum tolerated dose (MTD). [ Time Frame: Safety Blood samples weekly throughout dosing. Physical Examination every 3 weeks. ECG and vital signs at least every 3 weeks. ]; To investigate the safety and tolerability of AZD4547 when given orally to patients with advanced solid malignancies and define the maximum tolerated dose (MTD). [ Time Frame: Ophthalmology at baseline and 3 weeks after start of BD dosing. MUGA / Echocardiogram at baseline, 3 weeks after start of BD dosing, and then every 3 months. ]
Change History	Complete list of historical versions of study NCT00979134 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 3, 2011)	To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. [ Time Frame: PK samples out to 96 hours after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. ]; 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 [ Time Frame: Baseline assessment, then assessment every 6 weeks after start of treatment. ]
Original Secondary Outcome Measures ICMJE; (submitted: September 16, 2009)	To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after multiple dosing when given orally. [ Time Frame: PK samples out to 96 hours after single dose. Staeady State PK profile 3 weeks after start of BD dosing ]; 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 v1.1. [ Time Frame: Baseline assessment, then assessment every 6 weeks after start of treatment. ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Study is Designed to Assess the Safety and Tolerability of AZD4547 at Increasing Doses in Patients With Advanced Tumours
Official Title ICMJE	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
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 Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Cancer; Advanced Solid Malignancies
Intervention ICMJE	Drug: AZD4547 Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily; Drug: AZD4547 Patients start at a dose of 80 mg twice daily, with no washout; Drug: AZD4547 Single dose is followed by washout 5-10 days before multiple dose
Study Arms	Experimental: Part A Ascending doses of AZD4547 administered orally to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD) Intervention: Drug: AZD4547; Experimental: Part B Dose expansion phase, at the RD defined in Part A Intervention: Drug: AZD4547; Experimental: Part C Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A Intervention: Drug: AZD4547
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 28, 2014)	979
Original Estimated Enrollment ICMJE; (submitted: September 16, 2009)	36
Actual Study Completion Date	March 2015
Actual Primary Completion Date	February 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	25 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00979134
Other Study ID Numbers ICMJE	D2610C00001
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	AstraZeneca
Study Sponsor ICMJE	AstraZeneca
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Fabrice André, Dr Institut de cancérologie Gustave Roussy Study Director: Donal Landers, Dr AstraZeneca
PRS Account	AstraZeneca
Verification Date	June 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP