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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00979134
• Other study ID #: D2610C00001
• Status: Terminated
• Phase: Phase 1
• Start date: October 21, 2009
• Est. completion date: March 5, 2015

Study information

• Verified date: November 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 95
• Est. completion date: March 5, 2015
• Est. primary completion date: February 12, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 149 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Malignancies
• Cancer
• Neoplasms

Intervention

Drug:
• AZD4547
Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily
• AZD4547
Patients start at a dose of 80 mg twice daily, with no washout
• AZD4547
Single dose is followed by washout 5-10 days before multiple dose

Locations

Country	Name	City	State
France	Research Site	Pierre Benite
France	Research Site	Villejuif
Germany	Research Site	Frankfurt
Germany	Research Site	Freiburg
Germany	Research Site	Köln
Italy	Research Site	Napoli
Italy	Research Site	Rozzano
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Rotterdam
Spain	Research Site	Badajoz
Spain	Research Site	Majadahonda
Spain	Research Site	Valencia
Spain	Research Site	Valencia
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Newcastle upon Tyne
United Kingdom	Research Site	Wolverhampton
United States	Research Site	Aurora	Colorado
United States	Research Site	Detroit	Michigan
United States	Research Site	Houston	Texas
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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.
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.