Proof-of-Concept Study of AZD4547 in Patients With FGFR1 or FGFR2 Amplified Tumours (FGFR)

March 14, 2013 updated by: Royal Marsden NHS Foundation Trust
To assess the activity of the FGFR inhibitor AZD4547 in patients with FGFR1 or FGFR2 amplified breast, squamous lung and stomach cancer whose cancers have progressed following previous chemotherapy

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Primary endpoint

- To assess anti-tumour activity as change in tumour size at 8 weeks and the correlation with change in tumour ERK1/2 phosphorylation at day 10-14.

Secondary endpoints

  • Objective response rate to AZD4547 in all patients and in each tumour group
  • Safety and tolerability of AZD4547 in all patients
  • Disease control rate at 8 weeks
  • Progression free survival in all patients and in each tumour group

Study Type

Interventional

Enrollment (Anticipated)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Surrey
      • London and Surrey, Surrey, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • David Cunningham, MD FRCP
        • Sub-Investigator:
          • Nicholas Turner, MA MRCP PhD
        • Sub-Investigator:
          • Sanjay Popat, BSc MBBS MRCP PhD
        • Sub-Investigator:
          • Elizabeth Smyth, MB MRCP MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  • Female or male aged 25 years or older.
  • Mandatory provision of archival or fresh tumour biopsy for confirmation of FGFR gene amplification.
  • World Health Organisation performance status 0-2, minimum life expectancy of 12 weeks from proposed first dose date
  • Patient ability to comply with the collection of tumor biopsies which is mandatory at baseline and on days 10-14
  • Calcium and phosphate within normal limits.
  • At least one lesion, not previously irradiated, that can be accurately measured at baseline as >=10 mm in the longest diameter - except lymph nodes which must have short axis >=15 mm.
  • Local disease confined to the stomach or oesophagus is not considered measurable (patients with locally advanced gastro-oesophageal adenocarcinoma must have at least one measurable nodal lesion >=15mm in the short axis).

Tumour specific inclusion criteria

Advanced gastro-oesophageal adenocarcinoma

  • Histologically proven metastatic or locally advanced inoperable adenocarcinoma of the stomach, lower oesophagus or oesophago-gastric junction.
  • Documented progression after 1 or 2 prior courses of chemotherapy for advanced disease,
  • FGFR2 amplification

Advanced breast carcinoma

  • Histologically confirmed metastatic or locally advanced breast cancer, negative for HER2 as determined by local laboratory.
  • Patients with locally advanced disease must have recurrent, or progressive, disease that is not suitable for treatment with curative intent
  • Patients with ER positive disease must have been treated with at least one line of hormonal therapy for recurrent/progressive disease or have been on hormonal therapy at the time of recurrence/progression
  • Documented progression after at least one and no more than three prior courses of chemotherapy for advanced disease.
  • FGFR1 amplification

Advanced squamous cell lung cancer

  • Histologically confirmed metastatic or locally advanced squamous cell carcinoma of lung
  • Documented progression after 1 or 2 prior courses of chemotherapy for advanced disease
  • FGFR1 amplification

Exclusion criteria

  • Treatment potent inhibitors or inducers of CYP3A4, 2C8 or 2D6 or substrates of CYP3A4 within specified durations prior to the first dose of study treatment
  • Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment
  • Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks before the first dose of study treatment
  • Prior exposure to AZD4547 or any other drug with FGFR inhibition as its primary mode of action
  • Untreated brain metastases
  • Inadequate bone marrow reserve or organ function
  • Corrected total calcium > ULN
  • Total phosphate > ULN
  • Mean resting corrected QT interval > 470 msec obtained from 3 consecutive electrocardiograms (ECGs)
  • Any of the following ophthalmological criteria: 1)Current evidence or previous history of retinal pigmented epithelium detachment (RPED). 2)Previous laser treatment or intra-ocular injection for treatment of macular degeneration. 3) Current evidence or previous history of dry or wet age-related macular degeneration. 4) Current evidence or previous history of retinal vein occlusion (RVO). 5) Current evidence or previous history of retinal degenerative diseases (e.g. hereditary). 6) Current evidence or previous history of any other clinically relevant chorioretinal defect

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Treatment Arm
16-24 patients per tumour group will be treated with AZD4547 administered 80mg twice daily, 2 weeks on, 1 week off in 21 days cycles.
Drug: AZD 4547

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess anti-tumour activity as change in tumour size at 8 weeks and the correlation with change in tumour ERK1/2 phosphorylation at day 10-14.
Time Frame: Baseline (tumour size, pERK), day 14(pERK), and week 8(tumour size)
A primary objective of the study is to collect serial research biopsies at baseline and on treatment with AZD4547, to assess the molecular changes that occur in the tumour in response to AZD4547 treatment and correlate with change in tumour size assessed at 8 weeks.
Baseline (tumour size, pERK), day 14(pERK), and week 8(tumour size)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: Eight weeks from treatment initiation and then every 6 weeks thereafter
Response rate is assessed using RECIST 1.1 radiological response and centrally reviewed.
Eight weeks from treatment initiation and then every 6 weeks thereafter
Progression free survival
Time Frame: Time measured from baseline to disease progression or death from any cause (approximately 3-9 months)
Time measured from baseline to disease progression or death from any cause (approximately 3-9 months)
Disease control rate at eight weeks
Time Frame: Disease control rate will be calculated as the proportion of patients with CR/PR/SD at eight weeks from baseline
Disease control rate will be calculated as the proportion of patients with CR/PR/SD at eight weeks from baseline
Safety and tolerability of AZD4547
Time Frame: Toxicity is assessed from consent until 30 days following treatment cessation
Toxicity is assessed from consent until 30 days following treatment cessation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Royal Marsden NHS Foundation Trust

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: David Cunningham, MD FRCP, Royal Marsden NHS Foundation Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Anticipated)

September 1, 2014

Study Completion (Anticipated)

September 1, 2015

Study Registration Dates

First Submitted

January 31, 2013

First Submitted That Met QC Criteria

February 18, 2013

First Posted (Estimate)

February 21, 2013

Study Record Updates

Last Update Posted (Estimate)

March 15, 2013

Last Update Submitted That Met QC Criteria

March 14, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3689

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on AZD 4547

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bahamas

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe