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

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

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 Overview

• Status: Terminated
• Conditions: Cancer; Advanced Solid Malignancies
• Intervention / Treatment: Drug: AZD4547; Drug: AZD4547; Drug: AZD4547

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Pierre Benite, France, 69495
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Germany
  • Frankfurt, Germany, 60488
    • Research Site
  • Freiburg, Germany, 79106
    • Research Site
  • Köln, Germany, 50924
    • Research Site
• Italy
  • Napoli, Italy, 80131
    • Research Site
  • Rozzano, Italy, 20089
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Research Site
  • Rotterdam, Netherlands, 3015 CE
    • Research Site
• Spain
  • Badajoz, Spain, 06008
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Valencia, Spain, 46010
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Research Site
  • Edinburgh, United Kingdom, EH4 2XU
    • Research Site
  • Glasgow, United Kingdom, G12 0YN
    • Research Site
  • London, United Kingdom, W1G 6AD
    • Research Site
  • London, United Kingdom, W12 0NN
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Research Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • Research Site
• United States
  • California
    • Stanford, California, United States, 94305
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 149 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)	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
Experimental: Part B; Dose expansion phase, at the RD defined in Part A	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
Experimental: Part C; Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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.
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.
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.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2009
• Primary Completion (Actual): February 12, 2014
• Study Completion (Actual): March 5, 2015

Study Registration Dates

• First Submitted: September 16, 2009
• First Submitted That Met QC Criteria: September 16, 2009
• First Posted (Estimate): September 17, 2009

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Advanced Solid Malignancies; Squamous NSCLC; Gastric adenocarcinoma; FGFR; Tumour
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: D2610C00001