Study to Assess Safety and Tolerability of AZD4547 in Japanese Patient

A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD4547 in Japanese Patients With Advanced Solid Malignancies

The primary purpose of this study is to explore the safety and tolerability of AZD4547 in Japanese patients with advanced solid malignancies.

Study Overview

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

Detailed Description

A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD4547 in Japanese Patients with Advanced Solid Malignancies.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chuo-ku, Japan
    • Research Site
  • Nagoya-shi, Japan
    • Research Site
  • Sapporo-shi, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 150 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Japanese patients with advanced solid malignancies Over 25 years old Relatively good overall health other than cancer

Exclusion Criteria:

- Poor bone marrow function (not producing enough blood cells). Poor liver or kidney function. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the IP or previous significant bowel resection.

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

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD4547	Drug: AZD4547; film coated tablet, PO, twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of adverse events (based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0)general examination	General examination prior to IP administration in treatment cycles
Assessment of adverse events (based on CTCAE version 4.0)general examination	General examination on day 1 in cycle 0
Assessment of adverse events (based on CTCAE version 4.0)general examination	General examination day 21 in cycle 1.
Assessment of adverse events (based on CTCAE version 4.0), laboratory values	Laboratory assessment prior to IP administration in all treatment cycles
Assessment of adverse events (based on CTCAE version 4.0), laboratory values	Laboratory assessment on day 1 in cycle 0
Assessment of adverse events (based on CTCAE version 4.0), laboratory values	Laboratory assessment day 1 cycle 1.
Assessment of adverse events (based on CTCAE version 4.0), laboratory values	Laboratory assessment day 8 cycle 1.
Assessment of adverse events (based on CTCAE version 4.0), laboratory values	Laboratory assessment day 15 cycle 1.
Assessment of adverse events (based on CTCAE version 4.0), laboratory values	Laboratory assessment day 21 cycle 1.
Assessment of adverse events (based on CTCAE version 4.0), vital sign measurements	Vital sign measurements prior to IP administration in all treatment cycles
Assessment of adverse events (based on CTCAE version 4.0), vital sign measurements	Vital sign measurements day 1 in cycle 0
Assessment of adverse events (based on CTCAE version 4.0), vital sign measurements	Vital sign measurements day 2 in cycle 0
Assessment of adverse events (based on CTCAE version 4.0), vital sign measurements	Vital sign measurements day 8 in cycle 1.
Assessment of adverse events (based on CTCAE version 4.0), vital sign measurements	Vital sign measurements day 21 in cycle 1.
Assessment of adverse events (based on CTCAE version 4.0), left ventricular ejection fraction (LVEF)	LVEF prior to study administration
Assessment of adverse events (based on CTCAE version 4.0), LVEF	LVEF on day 21 in cycle 1.
Assessment of adverse events (based on CTCAE version 4.0), eye examination	Eye examination prior to study administration
Assessment of adverse events (based on CTCAE version 4.0), eye examination	Eye examination on day 21 in cycle 1.

Secondary Outcome Measures

Outcome Measure	Time Frame
Define the maximum tolerated dose (MTD) if possible or biological effective dose.	Up to 3 weeks
To explore the pharmacokinetics (PK) of AZD4547and metabolite in Japanese patients with advanced solid malignancies when given AZD4547 orally.	Schedule of PK assessment 1. AZD4547; blood Cycle0-day1 -day21; 27 point 2. AZD4547 metabolite; blood Cycle1-day21; 1 poin 3. AZD4547; urine Cycle1-day21; 1 point
To obtain a preliminary assessment of the anti-tumour effect of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1.	Schedule of CT/MRI etc-screeing-cycle1 day21-every 6 weeks-the end of treatment

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Paul Stockman, AstraZeneca; Principal Investigator: Hideo Saka, MD, PhD, National Hospital Organisation Nagoya Medical Centre; Principal Investigator: Yasuo Takahashi, MD, National Hospital OrganisationHokkaido Cancer Centre

Publications and helpful links

General Publications

• Saka H, Kitagawa C, Kogure Y, Takahashi Y, Fujikawa K, Sagawa T, Iwasa S, Takahashi N, Fukao T, Tchinou C, Landers D, Yamada Y. Safety, tolerability and pharmacokinetics of the fibroblast growth factor receptor inhibitor AZD4547 in Japanese patients with advanced solid tumours: a Phase I study. Invest New Drugs. 2017 Aug;35(4):451-462. doi: 10.1007/s10637-016-0416-x. Epub 2017 Jan 10.

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: September 30, 2010
• First Posted (Estimate): October 1, 2010

Study Record Updates

• Last Update Posted (Estimate): June 29, 2016
• Last Update Submitted That Met QC Criteria: June 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: cancer; Japanese; Phase I; dose escalation; advanced solid malignancies; solid tumours; FGFR TKI
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: D2610C00002