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Efficacy and Safety of AZD4547 Versus Paclitaxel in Patients With Advanced Gastric or Gastro-oesophageal Cancer (SHINE)

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ClinicalTrials.gov Identifier: NCT01457846
Recruitment Status : Terminated
First Posted : October 24, 2011
Results First Posted : March 7, 2017
Last Update Posted : March 7, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Gastro-oesophageal Junction Cancer
Gastric Cancer
Interventions Drug: AZD4547
Drug: paclitaxel
Enrollment 960
Recruitment Details 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.
Pre-assignment Details 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
Arm/Group Title AZD4547 Paclitaxel
Hide Arm/Group Description 80mg BD 2 weeks on/1 week off 80mg / m^2
Period Title: Overall Study
Started 41 30
Received Treatment 40 27
Did Not Receive Treatment 1 3
Ongoing Treatment at Data Cut-off 1 1
Completed 0 0
Not Completed 41 30
Reason Not Completed
Death before treatment             1             2
Did not receive treatment             0             1
Death             27             16
Unclassified reason for not completed             11             10
Withdrawal by Subject             1             1
Lost to Follow-up             1             0
Arm/Group Title Paclitaxel AZD4547 Total
Hide Arm/Group Description 80mg / m^2 80mg BD 2 weeks on/1 week off Total of all reporting groups
Overall Number of Baseline Participants 30 41 71
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 41 participants 71 participants
61.9  (10.65) 60.6  (11.38) 61.2  (11.02)
[1]
Measure Description: Age at time of screening
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 30 participants 41 participants 71 participants
<50 years 4 7 11
>=50 - < 65 years 13 20 33
>= 65 years 13 14 27
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 41 participants 71 participants
Female
8
  26.7%
12
  29.3%
20
  28.2%
Male
22
  73.3%
29
  70.7%
51
  71.8%
1.Primary Outcome
Title Median Progression Free Survival
Hide Description 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).
Time Frame Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title AZD4547 Paclitaxel
Hide Arm/Group Description:
80mg BD 2 weeks on/1 week off
80mg / m^2
Overall Number of Participants Analyzed 41 30
Measure Type: Number
Unit of Measure: months
1.8 3.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD4547, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9581
Comments 1-sided
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.57
Confidence Interval (2-Sided) 80%
1.12 to 2.21
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off)
Hide Description [Not Specified]
Time Frame Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title AZD4547 Paclitaxel
Hide Arm/Group Description:
80mg BD 2 weeks on/1 week off
80mg / m^2
Overall Number of Participants Analyzed 38 30
Measure Type: Number
Unit of Measure: Patients
27 18
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD4547, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8156
Comments 1-sided
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.31
Confidence Interval (2-Sided) 80%
0.89 to 1.95
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Objective Response Rate
Hide Description 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.
Time Frame Week 8 (±1 week) and then every 8 weeks (±1 week)
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title AZD4547 Paclitaxel
Hide Arm/Group Description:
80mg BD 2 weeks on/1 week off
80mg / m^2
Overall Number of Participants Analyzed 38 30
Measure Type: Number
Unit of Measure: Patients (%)
2.6 23.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD4547, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9970
Comments 1-sided
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.09
Confidence Interval (2-Sided) 80%
0.02 to 0.35
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage Change From Baseline at Week 8 in Target Lesion Size
Hide Description A negative change denotes a reduction in target lesion size. Percentage change from baseline in tumour size at 8 weeks in target lesion size.
Time Frame Baseline, Week 8 (±1 week)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set - all treated patients with at least one post baseline RECIST target lesion assessment scan
Arm/Group Title AZD4547 Paclitaxel
Hide Arm/Group Description:
80mg BD 2 weeks on/1 week off
80mg / m^2
Overall Number of Participants Analyzed 36 26
Mean (Standard Deviation)
Unit of Measure: Percentage change
28.4  (44.4) -1.1  (36.18)
5.Secondary Outcome
Title Percentage of Patients Without Progressive Disease at 8 Weeks
Hide Description 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
Time Frame Week 8 (±1 week)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set - all treated patients
Arm/Group Title AZD4547 Paclitaxel
Hide Arm/Group Description:
80mg BD 2 weeks on/1 week off
80mg / m^2
Overall Number of Participants Analyzed 41 30
Measure Type: Number
Unit of Measure: Percentage of patients
24.4 53.3
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD4547 Paclitaxel
Hide Arm/Group Description 80mg BD 2 weeks on/1 week off 80mg / m^2
All-Cause Mortality
AZD4547 Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
AZD4547 Paclitaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/40 (20.00%)      6/27 (22.22%)    
Blood and lymphatic system disorders     
Anaemia   1/40 (2.50%)  1 0/27 (0.00%)  0
Gastrointestinal disorders     
Dyspepsia   1/40 (2.50%)  1 0/27 (0.00%)  0
Dysphagia   0/40 (0.00%)  0 1/27 (3.70%)  1
Intestinal haemorrhage   1/40 (2.50%)  1 0/27 (0.00%)  0
Obstruction gastric   1/40 (2.50%)  1 0/27 (0.00%)  0
Stomatitis   1/40 (2.50%)  1 0/27 (0.00%)  0
Vomiting   1/40 (2.50%)  1 2/27 (7.41%)  2
General disorders     
Asthenia   0/40 (0.00%)  0 1/27 (3.70%)  1
Hepatobiliary disorders     
Bile duct obstruction   1/40 (2.50%)  1 0/27 (0.00%)  0
Infections and infestations     
Biliary tract infection   0/40 (0.00%)  0 1/27 (3.70%)  1
Lower respiratory tract infection   0/40 (0.00%)  0 1/27 (3.70%)  1
Pneumonia   1/40 (2.50%)  1 0/27 (0.00%)  0
Urinary tract infection   1/40 (2.50%)  1 0/27 (0.00%)  0
Investigations     
Blood bilirubin increased   1/40 (2.50%)  1 0/27 (0.00%)  0
Transaminases increases   1/40 (2.50%)  1 0/27 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism   0/40 (0.00%)  0 1/27 (3.70%)  1
Vascular disorders     
Arterial disorder   1/40 (2.50%)  1 0/27 (0.00%)  0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZD4547 Paclitaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   39/40 (97.50%)      26/27 (96.30%)    
Blood and lymphatic system disorders     
Anaemia   7/40 (17.50%)  7 6/27 (22.22%)  6
Neutropenia   2/40 (5.00%)  2 9/27 (33.33%)  9
Eye disorders     
Detatchment of retinal pigment epithelium   6/40 (15.00%)  6 0/27 (0.00%)  0
Dry eye   4/40 (10.00%)  4 0/27 (0.00%)  0
Macular degeneration   2/40 (5.00%)  2 0/27 (0.00%)  0
Gastrointestinal disorders     
Nausea   10/40 (25.00%)  10 6/27 (22.22%)  6
Vomiting   8/40 (20.00%)  8 5/27 (18.52%)  5
Stomatis   10/40 (25.00%)  10 2/27 (7.41%)  2
Abdominal pain upper   9/40 (22.50%)  9 0/27 (0.00%)  0
Dyspepsia   4/40 (10.00%)  4 1/27 (3.70%)  1
Dysphagia   0/40 (0.00%)  0 2/27 (7.41%)  2
Constipation   10/40 (25.00%)  10 5/27 (18.52%)  5
Abdominal pain   9/40 (22.50%)  9 5/27 (18.52%)  5
General disorders     
Fatigue   6/40 (15.00%)  6 8/27 (29.63%)  8
Oedema peripheral   4/40 (10.00%)  4 2/27 (7.41%)  2
Asthenia   11/40 (27.50%)  11 5/27 (18.52%)  5
Pyrexia   4/40 (10.00%)  4 2/27 (7.41%)  2
Hepatobiliary disorders     
Diarrhoea   6/40 (15.00%)  6 6/27 (22.22%)  6
Infections and infestations     
Lower respiratory tract infection   0/40 (0.00%)  0 3/27 (11.11%)  3
Urinary tract infections   2/40 (5.00%)  2 2/27 (7.41%)  2
Investigations     
Aspartate aminotransferase   7/40 (17.50%)  7 0/27 (0.00%)  0
Blood alkaline phosphatase increased   4/40 (10.00%)  4 1/27 (3.70%)  1
Blood phosphorus increased   3/40 (7.50%)  3 0/27 (0.00%)  0
Blood bilirubin increased   2/40 (5.00%)  2 0/27 (0.00%)  0
Alanine aminotransferase increased   6/40 (15.00%)  6 0/27 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite   16/40 (40.00%)  8/27 (29.63%) 
Dry mouth   9/40 (22.50%)  9 0/27 (0.00%)  0
Hyperkalaemia   2/40 (5.00%)  2 2/27 (7.41%)  2
Hyperphosphataemia   3/40 (7.50%)  3 0/27 (0.00%)  0
Hypokalaemia   1/40 (2.50%)  1 2/27 (7.41%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia   3/40 (7.50%)  3 0/27 (0.00%)  0
Myalgia   0/40 (0.00%)  0 3/27 (11.11%)  3
Back pain   1/40 (2.50%)  1 6/27 (22.22%)  6
Nervous system disorders     
Dizziness   3/40 (7.50%)  3 1/27 (3.70%)  1
Lethargy   1/40 (2.50%)  1 2/27 (7.41%)  2
Dysgeusia   6/40 (15.00%)  6 4/27 (14.81%)  4
Peripheral sensory neuropathy   0/40 (0.00%)  0 3/27 (11.11%)  3
Hypoaesthesia   0/40 (0.00%)  0 2/27 (7.41%)  2
Headache   4/40 (10.00%)  4 1/27 (3.70%)  1
Psychiatric disorders     
Neuropathy peripheral   1/40 (2.50%)  1 4/27 (14.81%)  4
Insomnia   2/40 (5.00%)  2 3/27 (11.11%)  3
Respiratory, thoracic and mediastinal disorders     
Dyspnoea   3/40 (7.50%)  3 1/27 (3.70%)  1
Dysphonia   2/40 (5.00%)  2 1/27 (3.70%)  1
Productive cough   0/40 (0.00%)  0 2/27 (7.41%)  2
Epistaxis   3/40 (7.50%)  3 1/27 (3.70%)  1
Skin and subcutaneous tissue disorders     
Alopecia   2/40 (5.00%)  2 13/27 (48.15%)  13
Dry skin   3/40 (7.50%)  3 1/27 (3.70%)  1
Onychomadesis   3/40 (7.50%)  3 0/27 (0.00%)  0
Nail discolouration   2/40 (5.00%)  2 1/27 (3.70%)  1
Onycholysis   2/40 (5.00%)  2 0/27 (0.00%)  0
Pruritus   2/40 (5.00%)  2 1/27 (3.70%)  1
Indicates events were collected by systematic assessment
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Donal Landers
Organization: Astrazeneca
Phone: +44 1625 231890
EMail: Donal.Landers@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01457846    
Other Study ID Numbers: D2610C00004
First Submitted: September 16, 2011
First Posted: October 24, 2011
Results First Submitted: February 11, 2016
Results First Posted: March 7, 2017
Last Update Posted: March 7, 2017