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

• ClinicalTrials.gov Identifier: NCT00979134
• Recruitment Status: Terminated
• First Posted: September 17, 2009
• Results First Posted: March 15, 2019
• Last Update Posted: March 15, 2019
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: September 16, 2009
• First Posted Date: September 17, 2009
• Results First Submitted Date: April 1, 2016
• Results First Posted Date: March 15, 2019
• Last Update Posted Date: March 15, 2019
• Actual Study Start Date: October 21, 2009
• Actual Primary Completion Date: February 12, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2018)

• Number of Patients Who Experienced at Least 1 AE [ Time Frame: 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. [ Time Frame: 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 With at Least 1 AE of CTCAE >=G3 [ Time Frame: 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 [ Time Frame: Ongoing up to discontinuation up to 30 day FU. ]
  To investigate the safety and tolerability of AZD4547
• Number of Participants Who Experienced at Least One SAE [ Time Frame: 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 [ Time Frame: 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

Original Primary Outcome Measures (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. ]

Current Secondary Outcome Measures (submitted: November 30, 2018)

• AUC(0-infinity) [ Time Frame: 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.
• Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR) [ Time Frame: 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
• Cmax (ng/mL) [ Time Frame: 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.
• Css,Max (ng/mL) [ Time Frame: 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) [ Time Frame: 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.

Original Secondary Outcome Measures (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study is Designed to Assess the Safety and Tolerability of AZD4547 at Increasing Doses in Patients With Advanced Tumours
• 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
• 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cancer
• Advanced Solid Malignancies

Intervention

• 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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 30, 2018): 95
• Original Estimated Enrollment (submitted: September 16, 2009): 36
• Actual Study Completion Date: March 5, 2015
• Actual Primary Completion Date: February 12, 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 to 149 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT00979134
• Other Study ID Numbers: D2610C00001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fabrice André, Dr; Institut de cancérologie Gustave Roussy
• Study Director: Donal Landers, Dr; AstraZeneca

• PRS Account: AstraZeneca
• Verification Date: November 2018