Proof-of-concept study of AZD 4547 in patients with FGFR1 or FGFR2 amplified tumours - FGFR

Royal Marsden Hospital NHS Foundation Trust0 sites20 target enrollmentNovember 22, 2011

ConditionsAdvanced Breast Cancer Advanced Lung Cancer Advanced Upper gastrointestinal cancer

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Advanced Breast Cancer Advanced Lung Cancer Advanced Upper gastrointestinal cancer
Sponsor: Royal Marsden Hospital NHS Foundation Trust
Enrollment: 20
Status: Active, not recruiting
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

November 22, 2011

End Date

December 21, 2018

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Royal Marsden Hospital NHS Foundation Trust

Eligibility Criteria

Inclusion Criteria

•1\. Provision of signed and dated, written informed consent prior to any study specific procedures. 2\. Female or male aged 25 years or older. 3\. Mandatory provision of archival or fresh tumour biopsy for confirmation of FGFR gene amplification. This must be confirmed by AstraZeneca approved laboratory. 4\. World Health Organisation performance status 0\-2, minimum life expectancy of 12 weeks from proposed first dose date, no deterioration within 2 weeks of screening and first dose. 5\. Patient ability to comply with the collection of tumor biopsies (mandatory at baseline and on days 12\-14 6\. 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) with CT or MRI and which is suitable for accurate repeated measurements. ? 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). 7\. Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child\-bearing potential. 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 as assessed by AZ approved laboratory 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 regimens for advanced disease. ? FGFR1 or FGFR2 amplification as assessed by AZ approved laboratory. Advanced non\-adenocarcinoma lung cancer ? Histologically confirmed metastatic or locally advanced non\-adenocarcinoma cell lung carcinoma. ? Documented progression after 1 or 2 prior courses of chemotherapy for advanced disease ? FGFR1 amplification as assessed by AZ approved laboratory
•Are the trial subjects under 18? no
•Number of subjects for this age range: 0
•F.1\.2 Adults (18\-64 years) yes
•F.1\.2\.1 Number of subjects for this age range 50
•F.1\.3 Elderly (\>\=65 years) yes
•F.1\.3\.1 Number of subjects for this age range 0

Exclusion Criteria

•Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1\. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 2\. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. 3\. Treatment with any of the following: ? Potent inhibitors or inducers of CYP3A4, 2C8 or 2D6 or substrates of CYP3A4 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 5\. With the exception of alopecia, any unresolved toxicities from prior therapy with a Common Terminology Criteria for Adverse Events (CTCAE) grade \>1 at the time of starting study treatment. 6\. Untreated brain metastases (patients with stable brain metastasis, 1 month post treatment are allowed in this study) 7\. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 8\. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: ? Absolute neutrophil count \< 1\.5 x 109/L. ? Platelet count \< 100 x 109/L. ? Haemoglobin \< 90 g/L. ? Alanine aminotransferase \> 2\.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases. ? Aspartate aminotransferase \> 2\.5 times ULN if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases. ? Total bilirubin \> 1\.5 times ULN. ? Creatinine \>1\.5 times ULN concurrent with creatinine clearance \< 50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is \> 1\.5 times ULN. ? Corrected total calcium \> ULN (corrected for albumin using a standard formula that will be specified in the protocol). ? Total phosphate \> ULN. 9\. Refractory nausea and vomiting, chronic gastrointestinal diseases that would preclude adequate oral intake and absorption of AZD4547\. 10\. Any of the following cardiac criteria: ? Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 consecutive electrocardiograms (ECGs). ? Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block. ? Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval. 11\. Pregnant or breast\-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication. 12\. History of hypersensitivity to active or inactive excipients of AZD4547 or other drugs with a similar chemical structure or class to AZD4547\. 13\. Judgment by the investigator that the patient