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

Royal Marsden NHS Foundation Trust

Status and phase

Unknown

Phase 2

Conditions

Oesophageal Cancer

Breast Cancer

Gastric Cancer

Squamous Cell Carcinoma of the Lung

Treatments

Drug: AZD 4547

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01795768

3689

Details and patient eligibility

About

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

Full 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

Enrollment

48 estimated patients

Sex

All

Ages

25+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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