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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- AstraZeneca
- Enrollment
- 95
- Locations
- 1
- Primary Endpoint
- Number of Participants With at Least 1 AE of CTCAE >=G3
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 25 Years to 149 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Part B
Dose expansion phase, at the RD defined in Part A
Intervention: AZD4547 (Drug)
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: AZD4547 (Drug)
Part C
Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A
Intervention: AZD4547 (Drug)
Outcomes
Primary Outcomes
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 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 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
Secondary Outcomes
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)