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

NCT01795768 | Unknown Phase 2 DMC

• 1 other identifier: 3689
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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

Conditions

Gastric Cancer; Oesophageal Cancer; Breast Cancer; Squamous Cell Carcinoma of the Lung

Keywords

Non randomised; Open label; Multicentre; Phase II biomarker study

Outcome Measures

Primary Outcomes (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.

  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 Outcomes (4)

• Response rate

  Eight weeks from treatment initiation and then every 6 weeks thereafter

• Progression free survival

  Time measured from baseline to disease progression or death from any cause (approximately 3-9 months)

• Disease control rate at eight weeks

  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

  Toxicity is assessed from consent until 30 days following treatment cessation

Study Arms (1)

Single Treatment Arm

EXPERIMENTAL

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

Interventions

AZD 4547 DRUG

Single Treatment Arm

Eligibility Criteria

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

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• AstraZeneca: collaborator

Study Sites (1)

Royal Marsden NHS Foundation Trust

London and Surrey, Surrey, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• David Cunningham, MD FRCP

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angela Gillbanks

CONTACT

+44(0)2086613156; angela.gillbanks@rmh.nhs.uk

Elizabeth Smyth, MB MRCP MSc

CONTACT

+44(0)2086613156; elizabeth.smyth@rmh.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 21, 2013
• Study Start: September 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2015
• Last Updated: March 15, 2013

Record last verified: 2013-03

Locations

GB (1)