Clinical Trials /

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

NCT01795768

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Proof-of-Concept Study of AZD4547 in Patients With FGFR1 or FGFR2 Amplified Tumours
  • Official Title: Proof-of-Concept Study of AZD4547 in Patients With FGFR1 or FGFR2 Amplified Tumours

Clinical Trial IDs

  • ORG STUDY ID: 3689
  • NCT ID: NCT01795768

Conditions

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

Interventions

DrugSynonymsArms
AZD 4547Single Treatment Arm

Purpose

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

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
    

Trial Arms

NameTypeDescriptionInterventions
Single Treatment ArmExperimental16-24 patients per tumour group will be treated with AZD4547 administered 80mg twice daily, 2 weeks on, 1 week off in 21 days cycles.
  • AZD 4547

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:25 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description: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

Measure:Response rate
Time Frame:Eight weeks from treatment initiation and then every 6 weeks thereafter
Safety Issue:
Description:Response rate is assessed using RECIST 1.1 radiological response and centrally reviewed.
Measure:Progression free survival
Time Frame:Time measured from baseline to disease progression or death from any cause (approximately 3-9 months)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Safety and tolerability of AZD4547
Time Frame:Toxicity is assessed from consent until 30 days following treatment cessation
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Royal Marsden NHS Foundation Trust

Trial Keywords

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

Last Updated

March 14, 2013