Clinical trial NCT01457846: Efficacy and Safety of AZD4547 Versus Paclitaxel in Patients With Advanced Gastric or Gastro-oesophageal Cancer
Official title: A Randomised Open-Label Phase II Study to Assess the Efficacy & Safety of AZD4547 Monotherapy Versus Paclitaxel in Patients With Advanced Gastric Adenocarcinoma (Inc. Adenocarcinoma of the Lower Third of the Oesophagus or the Gastro-Oesophageal Junction)With FGFR2 Polysomy or Gene Amplification.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastro-oesophageal Junction Cancer
Gastric Cancer
Keywords: gastro-oesophageal junction cancer
gastric cancer
lower third oesophageal cancer
polysomy
amplification
FGFR
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-10-24
Enrollment: 960
Sex: ALL
Minimum age (years): 25
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy, safety and tolerability of AZD4547 compared with paclitaxel in patients with advanced gastric or lower-oesophageal cancer whose tumours are found to have FGFR2 polysomy or gene amplification.

Detailed description: A Randomised Open-Label Phase IIa Study to Assess the Efficacy and Safety of AZD4547 monotherapy versus paclitaxel in Patients with Advanced Gastric or Gastro-oesophageal Junction Cancer with FGFR2 Polysomy or Gene Amplification (SHINE study). Patients were to be assigned to strata by FGFR2 status of: polysomy, low or high gene amplification.

Eligibility 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 1 prior chemotherapy or chemoradiotherapy for gastric cancer. Suitable for and expected to benefit from paclitaxel monotherapy.
* At least one lesion, not previously irradiated, that has baseline at least 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

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 cremophor 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 Echocardiogram (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.

Primary outcomes:
measure: Median Progression Free Survival
timeFrame: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)
Secondary outcomes:
measure: Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off)
timeFrame: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)
measure: Objective Response Rate
timeFrame: Week 8 (±1 week) and then every 8 weeks (±1 week)
measure: Percentage Change From Baseline at Week 8 in Target Lesion Size
timeFrame: Baseline, Week 8 (±1 week)
measure: Percentage of Patients Without Progressive Disease at 8 Weeks
timeFrame: Week 8 (±1 week)
Other outcomes:
Locations:
city: Brussels (Anderlecht)
country: Belgium
facility: Research Site
city: Brussels (Woluwé-St-Lambert)
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Vratza
country: Bulgaria
facility: Research Site
city: Fredericton
country: Canada
facility: Research Site
state: New Brunswick
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Brno
country: Czech Republic
facility: Research Site
city: Olomouc
country: Czech Republic
facility: Research Site
city: Praha 2
country: Czech Republic
facility: Research Site
city: Saint Cloud
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Chennai
country: India
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
city: Nagpur
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Vellore
country: India
facility: Research Site
city: Ancona
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Anyang-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Hwasun-gun
country: Korea, Republic of
facility: Research Site
city: Jeonju-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Keelung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Aberdeen
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Maidstone
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Paul Stockman, MD PHD
role: STUDY_DIRECTOR
affiliation: University Hospital, Gasthuisberg
name: Eric Van Cutsem, MD PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Hospital
name: Yung-Jue Bang, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: