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

NCT00979134 | Terminated Phase 1 Results

• 1 other identifier: D2610C00001
• Study Type: interventional
• Target: 95
• Locations: 7 countries
• Sites: 29

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.

Conditions

Cancer; Advanced Solid Malignancies

Keywords

Cancer; Tumour; Advanced Solid Malignancies; FGFR; Squamous NSCLC; Gastric adenocarcinoma

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (3)

Part A

EXPERIMENTAL

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

Part B

EXPERIMENTAL

Dose expansion phase, at the RD defined in Part A

Drug: AZD4547

Part C

EXPERIMENTAL

Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A

Drug: AZD4547

Interventions

AZD4547 DRUG

Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily

Part B

Eligibility Criteria

• Age: 25 Years - 149 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (29)

Research Site

Stanford, California, 94305, United States

Location

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

New Haven, Connecticut, 06520, United States

Location

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Detroit, Michigan, 48201, United States

Location

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New York, New York, 10021, United States

Location

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Philadelphia, Pennsylvania, 19111, United States

Location

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Nashville, Tennessee, 37232, United States

Location

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Houston, Texas, 77030, United States

Location

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Pierre-Bénite, 69495, France

Location

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Villejuif, 94805, France

Location

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Cologne, 50924, Germany

Location

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Frankfurt, 60488, Germany

Location

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Freiburg im Breisgau, 79106, Germany

Location

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Napoli, 80131, Italy

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Rozzano, 20089, Italy

Location

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Amsterdam, 1066 CX, Netherlands

Location

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Rotterdam, 3015 CE, Netherlands

Location

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Badajoz, 06008, Spain

Location

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Majadahonda, 28222, Spain

Location

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Valencia, 46010, Spain

Location

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Valencia, 46026, Spain

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Birmingham, B9 5SS, United Kingdom

Location

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Edinburgh, EH4 2XU, United Kingdom

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Glasgow, G12 0YN, United Kingdom

Location

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London, W12 0NN, United Kingdom

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London, W1G 6AD, United Kingdom

Location

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Manchester, M20 4BX, United Kingdom

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Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

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Wolverhampton, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

AZD4547

Limitations and Caveats

Due to early termination no AUC(inf), Cmax, Css,max and AUC,ss for Part C (PK). Data from 33 patients after 22 days of multiple dosing in Part A \& limited data for part B only. 1 subject not dosed, so pre-stated subject number 95, total with data 94.

Results Point of Contact

• Title: Donal Landers
• Organization: AstraZeneca

Donal.Landers@astrazeneca.com

+44 1625 231890

Study Officials

• Fabrice André, Dr

  Institut de cancérologie Gustave Roussy

  PRINCIPAL INVESTIGATOR

• Donal Landers, Dr

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2009
• First Posted: September 17, 2009
• Study Start: October 21, 2009
• Primary Completion: February 12, 2014
• Study Completion: March 5, 2015
• Last Updated: March 15, 2019
• Results First Posted: March 15, 2019

Record last verified: 2018-11

Locations

DE (3); NL (2); GB (8); US (8); IT (2); FR (2); ES (4)