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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD4547 | Experimental | AZD4547 taken orally in tablet formation, 80mg b.d., in a 2 week on, 1 week off schedule |
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| 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) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD4547 | Drug | Tablets taken, oral, twice daily, commencing with a 2 week on AZD4547, 1 week off AZD4547 schedule. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul Stockman, MD PHD | AstraZeneca | Study Director |
| Eric Van Cutsem, MD PHD | University Hospital, Gasthuisberg | Principal Investigator |
| Yung-Jue Bang, MD, PHD | Seoul National University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Brussels (Anderlecht) | Belgium | ||||
| Research Site |
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| Label | URL |
|---|---|
| D2610C00004redacted\_protocol | View source |
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Patients ≥ 25 years with locally advanced or metastatic gastric adenocarcinoma that had FGFR2 polysomy or FGFR2 gene amplification and whose disease had progressed during or after 1st line therapy. Patients whose disease had progressed within 6 months following adjuvant or neo-adjuvant therapy could be included at the discretion of the investigator
This study was conducted in 11 countries. Enrolment started in November 2011 and last patient visit was in August 2013. In total, 960 patients were enrolled out of which 71 were randomised. A total of 67 patients received treatment , 40 of these patients received AZD4547 and 27 received Paclitaxel.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZD4547 | 80mg BD 2 weeks on/1 week off |
| FG001 | Paclitaxel | 80mg / m^2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| paclitaxel | Drug | Infusion administered once a week, 3 weeks on and 1 week off |
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| 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. | 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 | Week 8 (±1 week) |
| Brussels (Woluwé-St-Lambert) |
| Belgium |
| Research Site | Leuven | Belgium |
| Research Site | Liège | Belgium |
| Research Site | Plovdiv | Bulgaria |
| Research Site | Sofia | Bulgaria |
| Research Site | Vratsa | Bulgaria |
| Research Site | Fredericton | New Brunswick | Canada |
| Research Site | Toronto | Ontario | Canada |
| Research Site | Brno | Czechia |
| Research Site | Olomouc | Czechia |
| Research Site | Prague | Czechia |
| Research Site | Saint-Cloud | France |
| Research Site | Villejuif | France |
| Research Site | Hamburg | Germany |
| Research Site | Mainz | Germany |
| Research Site | Budapest | Hungary |
| Research Site | Debrecen | Hungary |
| Research Site | Nyíregyháza | Hungary |
| Research Site | Bangalore | India |
| Research Site | Chennai | India |
| Research Site | Hyderabad | India |
| Research Site | Nagpur | India |
| Research Site | Pune | India |
| Research Site | Vellore | India |
| Research Site | Ancona | Italy |
| Research Site | Milan | Italy |
| Research Site | Pisa | Italy |
| Research Site | Roma | Italy |
| Research Site | Chiba | Japan |
| Research Site | Chūōku | Japan |
| Research Site | Kōtoku | Japan |
| Research Site | Nagoya | Japan |
| Research Site | Sapporo | Japan |
| Research Site | Takatsuki-shi | Japan |
| Research Site | Brasov | Romania |
| Research Site | Cluj-Napoca | Romania |
| Research Site | Anyang-si | South Korea |
| Research Site | Daegu | South Korea |
| Research Site | Hwasun-gun | South Korea |
| Research Site | Jeonju | South Korea |
| Research Site | Seongnam-si | South Korea |
| Research Site | Seoul | South Korea |
| Research Site | A Coruña | Spain |
| Research Site | Barcelona | Spain |
| Research Site | Madrid | Spain |
| Research Site | Oviedo | Spain |
| Research Site | Santander | Spain |
| Research Site | Seville | Spain |
| Research Site | Keelung | Taiwan |
| Research Site | Taichung | Taiwan |
| Research Site | Taipei | Taiwan |
| Research Site | Taoyuan | Taiwan |
| Research Site | Kharkiv | Ukraine |
| Research Site | Lviv | Ukraine |
| Research Site | Aberdeen | United Kingdom |
| Research Site | London | United Kingdom |
| Research Site | Maidstone | United Kingdom |
| Research Site | Manchester | United Kingdom |
| Research Site | Sutton | United Kingdom |
| Research Site | Wolverhampton | United Kingdom |
| Received Treatment |
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| Did Not Receive Treatment |
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| Ongoing Treatment at Data Cut-off |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Paclitaxel | 80mg / m^2 |
| BG001 | AZD4547 | 80mg BD 2 weeks on/1 week off |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at time of screening | Mean | Standard Deviation | years |
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| Age, Customized | Number | Participants |
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| Gender | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Full analysis set | Posted | Number | months | Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week) |
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| Secondary | Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off) | This secondary analysis included factors for treatment and FGFR2 FISH score (4/5 versus 6) and is based on the Full analysis set (all treated patients). | Posted | Number | Patients | Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week) |
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| Secondary | 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. | The analysis included factors for treatment and FGFR2 FISH score (4/5 versus 6) and is based on the Full analysis set (all treated patients). | Posted | Number | Patients (%) | Week 8 (±1 week) and then every 8 weeks (±1 week) |
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| Secondary | 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. | Full analysis set - all treated patients with at least one post baseline RECIST target lesion assessment scan | Posted | Mean | Standard Deviation | Percentage change | Baseline, Week 8 (±1 week) |
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| Secondary | 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 | Full analysis set - all treated patients | Posted | Number | Percentage of patients | Week 8 (±1 week) |
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AEs will be collected throughout the study, from randomisation until the end of the follow-up period. The follow-up period is defined as 28 days after study treatment (AZD4547 or paclitaxel) is discontinued.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZD4547 | 80mg BD 2 weeks on/1 week off | 8 | 40 | 39 | 40 | ||
| EG001 | Paclitaxel | 80mg / m^2 | 6 | 27 | 26 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Biliary tract infection | Infections and infestations | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Arterial disorder | Vascular disorders | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
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| Bile duct obstruction | Hepatobiliary disorders | Systematic Assessment |
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| Asthenia | General disorders | Systematic Assessment |
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| Blood bilirubin increased | Investigations | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
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| Intestinal haemorrhage | Gastrointestinal disorders | Systematic Assessment |
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| Obstruction gastric | Gastrointestinal disorders | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | Systematic Assessment |
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| Pneumonia | Infections and infestations | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | Systematic Assessment |
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| Transaminases increases | Investigations | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Detatchment of retinal pigment epithelium | Eye disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Diarrhoea | Hepatobiliary disorders | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | Systematic Assessment |
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| Aspartate aminotransferase | Investigations | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Urinary tract infections | Infections and infestations | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Dry eye | Eye disorders | Systematic Assessment |
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| Macular degeneration | Eye disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Oedema peripheral | General disorders | Systematic Assessment |
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| Asthenia | General disorders | Systematic Assessment |
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| Stomatis | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | Systematic Assessment |
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| Blood phosphorus increased | Investigations | Systematic Assessment |
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| Blood bilirubin increased | Investigations | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Lethargy | Nervous system disorders | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | Systematic Assessment |
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| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Onychomadesis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Nail discolouration | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Onycholysis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Dry mouth | Metabolism and nutrition disorders | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Pyrexia | General disorders | Systematic Assessment |
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| Neuropathy peripheral | Psychiatric disorders | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyperphosphataemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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Prompted by slow recruitment, AZ and the SRC instigated unscheduled analysis of the efficacy and tolerability. It was concluded that the study was unlikely to meet its primary objective. Enrolment ceased and the study closed.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Donal Landers | Astrazeneca | +44 1625 231890 | Donal.Landers@astrazeneca.com |
| ID | Term |
|---|---|
| D013274 | Stomach Neoplasms |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
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| ID | Term |
|---|---|
| C572463 | AZD4547 |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
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| >=50 - < 65 years |
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| >= 65 years |
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| Male |
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