FGFR, Amplification, polysomy, gastro-oesophageal junction cancer, lower third oesophageal cancer, gastric cancer, randomised, efficacy MedDRA version: 14.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10
Conditions
Interventions
Product Name: AZD4547 20mg white film-coated tablet
Product Code: AZD4547
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not available
Sponsors
AstraZeneca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Female or male aged 25 or over Histological diagnosis of locally advanced or metastatic gastro adenocarcinoma (including adenocarcinoma of the lower third of the oesophagus or the gastro oesophageal junction ) Radiographically confirmed progression after first line treatment for advanced/metastatic gastric cancer. Suitable for and expected to benefit from paclitaxel monotherapy At least one lesion, not previously irradiated, that at baseline is equal to or larger than 10mm in the longest diameter for non nodal lesions and is assessed by Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) Provision of either an archival tumour sample or a fresh tumour sample for confirmation of FGFR2 polysomy/gene amplification Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: Prior exposure to AZD4547 or history of hypersensitivity other drugs similar in structure or class to AZD4547. Hypersensitivity to paclitaxel or formulated in Cremaphor EL (polyoxyethylated castor oil) Prior taxane treatment for gastric cancer with the exception of adjuvant/neo-adjuvant therapy given > 6 months Major surgery, radiotherapy with wide field of radiation or any cancer treatment within 4 weeks before the first dose of the study treatment With the exception of alopecia, any unresolved toxicities from prior therapy with a Common Terminology Criteria for AE (CTCAE) grade >1 at the time of starting study treatment. Blood and ECG readings that are deemed to be abnormal by falling outside of the reference ranges in the protocol inclusion/exclusion section. Taking other regular medication that are predicted to interact with AZD4547 due to their route of metabolism.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Investigate the efficacy of AZD4547 vs paclitaxel by assessment of Progression-Free Survival (PFS) in: all randomised patients, patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone; Secondary Objective: Overall Survival, Objective Response Rate, % patients without progression & change in tumour size at 8 weeks, duration of response Safety & tolerability AZD4547 PK & exposure/PD endpoint relationship Quality of life, disease symptoms, WHO performance status ;Primary end point(s): Investigate the efficacy of AZD4547 vs paclitaxel by assessment of Progression-Free Survival in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone;Timepoint(s) of evaluation of this end point: RECIST assessments will be performed at baseline and every 8 weeks until progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Investigate the efficacy of AZD4547 vs paclitaxel by comparison of Overall Survival in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone. Investigate the efficacy of AZD4547 vs. paclitaxel by comparison of the change in tumour size at 8 weeks in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone. Efficacy of AZD4547 vs paclitaxel by comparison of objective response rate and duration of response in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone. Efficacy of AZD4547 vs paclitaxel by comparison of % of patients without progression disease at 8 weeks in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone. Safety and tolerability of AZD4547 vs paclitaxel by assessing changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis), vital signs & adverse events. Investigate pharmacokinetics of AZD4547 in patients receiving AZD4547. Investigate possible relationships between plasma AZD4547 and levels of bFGF, FGF23 & phosphate. Disease-related symptom changes & time to symptom progression in patients receiving AZD4547/paclitaxel in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone. Changes in and time to deterioration of Health Related Quality of Life in patients receiving AZD4547/paclitaxel in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone. Changes in, and time to det | — |
Countries
Belgium, Brazil, Bulgaria, Canada, Czech Republic, France, Germany, Hungary, India, Italy, Japan, Korea, Republic of, Romania, Russian Federation, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed