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

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ClinicalTrials.gov Identifier: NCT00979134
Recruitment Status : Terminated (

Termination of study enrolment to Part C, Cohort 3 (08 July 2013) was based on the analysis of data from Study D2610C00004.

Data were available from 33 patient

)
First Posted : September 17, 2009
Results First Posted : March 15, 2019
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Cancer Advanced Solid Malignancies Drug: AZD4547 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 21, 2009
Actual Primary Completion Date : February 12, 2014
Actual Study Completion Date : March 5, 2015

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

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

Experimental: Part C
Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A
Drug: AZD4547
Patients start at a dose of 80 mg twice daily, with no washout




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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 Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 149 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00979134


  Show 29 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Fabrice André, Dr Institut de cancérologie Gustave Roussy
Study Director: Donal Landers, Dr AstraZeneca

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00979134     History of Changes
Other Study ID Numbers: D2610C00001
First Posted: September 17, 2009    Key Record Dates
Results First Posted: March 15, 2019
Last Update Posted: March 15, 2019
Last Verified: November 2018
Keywords provided by AstraZeneca:
Cancer
Tumour
Advanced Solid Malignancies
FGFR
Squamous NSCLC
Gastric adenocarcinoma
Additional relevant MeSH terms:
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Neoplasms