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

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ClinicalTrials.gov Identifier: NCT01795768
Recruitment Status : Unknown
Verified March 2013 by Royal Marsden NHS Foundation Trust.
Recruitment status was:  Recruiting
First Posted : February 21, 2013
Last Update Posted : March 15, 2013
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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

Condition or disease Intervention/treatment Phase
Gastric Cancer Oesophageal Cancer Breast Cancer Squamous Cell Carcinoma of the Lung Drug: AZD 4547 Phase 2

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Proof-of-Concept Study of AZD4547 in Patients With FGFR1 or FGFR2 Amplified Tumours
Study Start Date : September 2012
Estimated Primary Completion Date : September 2014
Estimated Study Completion Date : September 2015


Arms and Interventions

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


Outcome Measures

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Progression free survival [ Time Frame: Time measured from baseline to disease progression or death from any cause (approximately 3-9 months) ]
  3. 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 ]
  4. Safety and tolerability of AZD4547 [ Time Frame: Toxicity is assessed from consent until 30 days following treatment cessation ]

Eligibility Criteria

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Ages Eligible for Study:   25 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

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): NCT01795768


Contacts
Contact: Angela Gillbanks +44(0)2086613156 angela.gillbanks@rmh.nhs.uk
Contact: Elizabeth Smyth, MB MRCP MSc +44(0)2086613156 elizabeth.smyth@rmh.nhs.uk

Locations
United Kingdom
Royal Marsden NHS Foundation Trust Recruiting
London and Surrey, Surrey, United Kingdom, SM2 5PT
Contact: Angela Gillbanks    +44(0)2086613156    angela.gillbanks@rmh.nhs.uk   
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         
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
AstraZeneca
Investigators
Principal Investigator: David Cunningham, MD FRCP Royal Marsden NHS Foundation Trust
More Information

Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01795768     History of Changes
Other Study ID Numbers: 3689
First Posted: February 21, 2013    Key Record Dates
Last Update Posted: March 15, 2013
Last Verified: March 2013

Keywords provided by Royal Marsden NHS Foundation Trust:
Non randomised
Open label
Multicentre
Phase II biomarker study

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Stomach Neoplasms
Lung Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases