Gastro-oesophageal Junction CancerPhase 2SHINENCT01457846
Efficacy and Safety of AZD4547 Versus Paclitaxel in Patients With Advanced Gastric or Gastro-oesophageal Cancer
A Phase 2 study testing AZD4547 and paclitaxel in people with Gastro-oesophageal Junction Cancer and Gastric Cancer, run by AstraZeneca at 61 sites in 16 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 130 years
- Conditions the study is for
- Gastro-oesophageal Junction Cancer, Gastric Cancer
- What is being tested?
- AZD4547 and paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 960 participants
- Where
- 61 sitesin 16 countries
- Study dates
- Nov 2011to Feb 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
61 sites in 16 countries.
61 sites in 16 countries
India6 sites
Research Site
Bangalore
Research Site
Chennai
Research Site
Hyderabad
Research Site
Nagpur
Research Site
Pune
Research Site
Vellore
Japan6 sites
Research Site
Chiba
Research Site
Chūōku
Research Site
Kōtoku
Research Site
Nagoya
Research Site
Sapporo
Research Site
Takatsuki-shi
South Korea6 sites
Research Site
Anyang-si
Research Site
Daegu
Research Site
Hwasun-gun
Research Site
Jeonju
Research Site
Seongnam-si
Research Site
Seoul
Spain6 sites
Research Site
A Coruña
Research Site
Barcelona
Research Site
Madrid
Research Site
Oviedo
Research Site
Santander
Research Site
Seville
United Kingdom6 sites
Research Site
Aberdeen
Research Site
London
Research Site
Maidstone
Research Site
Manchester
Research Site
Sutton
Research Site
Wolverhampton
Belgium4 sites
Research Site
Brussels (Anderlecht)
Research Site
Brussels (Woluwé-St-Lambert)
Research Site
Leuven
Research Site
Liège
Italy4 sites
Research Site
Ancona
Research Site
Milan
Research Site
Pisa
Research Site
Roma
Taiwan4 sites
Research Site
Keelung
Research Site
Taichung
Research Site
Taipei
Research Site
Taoyuan
Hungary3 sites
Research Site
Budapest
Research Site
Debrecen
Research Site
Nyíregyháza
Canada2 sites
Research Site
Fredericton, New Brunswick
Research Site
Toronto, Ontario
About this study
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.
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.
Read the 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.
- Conditions
- Gastro-oesophageal Junction Cancer, Gastric Cancer
- Being tested
- AZD4547, paclitaxel
- Keywords
- gastro-oesophageal junction cancer, gastric cancer, lower third oesophageal cancer, polysomy, amplification, FGFR
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4547Drug
Tablets taken, oral, twice daily, commencing with a 2 week on AZD4547, 1 week off AZD4547 schedule.
paclitaxelDrug
Infusion administered once a week, 3 weeks on and 1 week off
| Study group | Role | What they receive |
|---|---|---|
| AZD4547 | Experimental | AZD4547 taken orally in tablet formation, 80mg b.d., in a 2 week on, 1 week off schedule Receives: Drug: AZD4547 |
| Paclitaxel | Active comparator | Paclitaxel - 80mg/m² as a 1 hour infusion given weekly on days 1, 8 and 15 of a 28 day cycle (up to the maximum number of cycles per local practice) Receives: Drug: paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression Free Survival
PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression).
Measured: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)
Secondary outcomes (4)
Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off)
Measured: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)
Objective Response Rate
ORR=Percentage of patients with at least one visit response of CR (complete response) or PR (partial response) that is confirmed at least 4 weeks later; CR:disappearance of target lesions and no new lesions; PR is at least 30% decrease in sum of diameters of lesions taking as a reference the smallest sum since treatment started.
Measured: Week 8 (±1 week) and then every 8 weeks (±1 week)
Percentage Change From Baseline at Week 8 in Target Lesion Size
A negative change denotes a reduction in target lesion size. Percentage change from baseline in tumour size at 8 weeks in target lesion size.
Measured: Baseline, Week 8 (±1 week)
Percentage of Patients Without Progressive Disease at 8 Weeks
PD = A ≥ 20% increase in the sum of diameters of target lesions and an absolute increase of ≥ 5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diamters
Measured: Week 8 (±1 week)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionAug 2013
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastro-oesophageal Junction CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 960 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Stockman, MD PHD, Study director, AstraZenecaEric Van Cutsem, MD PHD, Principal investigator, University Hospital, GasthuisbergYung-Jue Bang, MD, PHD, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01457846
- Sponsor's protocol ID
- D2610C00004
- Acronym
- SHINE
- Status last verified
- Jan 2017
- First submitted
- 16 Sep 2011
- Last updated
- 7 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01457846
- Acronym / sponsor ID
- SHINE / D2610C00004
- Conditions
- Gastro-oesophageal Junction Cancer, Gastric Cancer
- Keywords
- gastro-oesophageal junction cancer, gastric cancer, lower third oesophageal cancer, polysomy, amplification, FGFR
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 960 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 24 Oct 2011 (estimated)
- Results
- Posted 7 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD4547 | Experimental | Drug: AZD4547AZD4547 taken orally in tablet formation, 80mg b.d., in a 2 week on, 1 week off schedule |
| Paclitaxel | Active comparator | Drug: paclitaxelPaclitaxel - 80mg/m² as a 1 hour infusion given weekly on days 1, 8 and 15 of a 28 day cycle (up to the maximum number of cycles per local practice) |
Who may qualify
- Ages
- 25 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4547Tablets taken, oral, twice daily, commencing with a 2 week on AZD4547, 1 week off AZD4547 schedule. | Drug | AZD4547 |
| paclitaxelInfusion administered once a week, 3 weeks on and 1 week off | Drug | Paclitaxel |
Primary outcome
Median Progression Free Survival
Time frame: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)
PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression).
4 secondary outcomes
Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off)
Time frame: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)
Objective Response Rate
Time frame: Week 8 (±1 week) and then every 8 weeks (±1 week)
Percentage Change From Baseline at Week 8 in Target Lesion Size
Time frame: Baseline, Week 8 (±1 week)
Percentage of Patients Without Progressive Disease at 8 Weeks
Time frame: Week 8 (±1 week)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- D2610C00004redacted\_protocolLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Stockman, MD PHD study director
AstraZeneca
Eric Van Cutsem, MD PHD principal investigator
University Hospital, Gasthuisberg
Yung-Jue Bang, MD, PHD principal investigator
Seoul National University Hospital
61 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD4547 and paclitaxel in people with Gastro-oesophageal Junction Cancer and Gastric Cancer, run by AstraZeneca at 61 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in India, Japan, South Korea, Spain, United Kingdom and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Progression Free Survival (time frame: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2017; AzTrials last refreshed its copy on 8 Nov 2026.