Trial Outcomes & Findings for Efficacy and Safety of AZD4547 Versus Paclitaxel in Patients With Advanced Gastric or Gastro-oesophageal Cancer (NCT NCT01457846)

Last Updated: 2017-03-07

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

960 participants

Primary outcome timeframe

Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)

Results posted on

2017-03-07

Participant Flow

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.

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

Participant milestones

Participant milestones
Measure	AZD4547 80mg BD 2 weeks on/1 week off	Paclitaxel 80mg / m\^2
Overall Study STARTED	41	30
Overall Study Received Treatment	40	27
Overall Study Did Not Receive Treatment	1	3
Overall Study Ongoing Treatment at Data Cut-off	1	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	41	30

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD4547 80mg BD 2 weeks on/1 week off	Paclitaxel 80mg / m\^2
Overall Study Death before treatment	1	2
Overall Study Did not receive treatment	0	1
Overall Study Death	27	16
Overall Study Unclassified reason for not completed	11	10
Overall Study Withdrawal by Subject	1	1
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paclitaxel n=30 Participants 80mg / m\^2	AZD4547 n=41 Participants 80mg BD 2 weeks on/1 week off	Total n=71 Participants Total of all reporting groups
Age, Continuous	61.9 years STANDARD_DEVIATION 10.65 • n=99 Participants	60.6 years STANDARD_DEVIATION 11.38 • n=107 Participants	61.2 years STANDARD_DEVIATION 11.02 • n=206 Participants
Age, Customized <50 years	4 Participants n=99 Participants	7 Participants n=107 Participants	11 Participants n=206 Participants
Age, Customized >=50 - < 65 years	13 Participants n=99 Participants	20 Participants n=107 Participants	33 Participants n=206 Participants
Age, Customized >= 65 years	13 Participants n=99 Participants	14 Participants n=107 Participants	27 Participants n=206 Participants
Gender Female	8 Participants n=99 Participants	12 Participants n=107 Participants	20 Participants n=206 Participants
Gender Male	22 Participants n=99 Participants	29 Participants n=107 Participants	51 Participants n=206 Participants

PRIMARY outcome

Timeframe: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)

Population: Full analysis set

Outcome measures

Outcome measures
Measure	AZD4547 n=41 Participants 80mg BD 2 weeks on/1 week off	Paclitaxel n=30 Participants 80mg / m\^2
Median Progression Free Survival	1.8 months	3.5 months

SECONDARY outcome

Timeframe: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week)

Population: 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).

Outcome measures

Outcome measures
Measure	AZD4547 n=38 Participants 80mg BD 2 weeks on/1 week off	Paclitaxel n=30 Participants 80mg / m\^2
Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off)	27 Patients	18 Patients

SECONDARY outcome

Timeframe: Week 8 (±1 week) and then every 8 weeks (±1 week)

Population: 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).

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.

Outcome measures

Outcome measures
Measure	AZD4547 n=38 Participants 80mg BD 2 weeks on/1 week off	Paclitaxel n=30 Participants 80mg / m\^2
Objective Response Rate	2.6 Patients (%)	23.3 Patients (%)

SECONDARY outcome

Timeframe: Baseline, Week 8 (±1 week)

Population: Full analysis set - all treated patients with at least one post baseline RECIST target lesion assessment scan

A negative change denotes a reduction in target lesion size. Percentage change from baseline in tumour size at 8 weeks in target lesion size.

Outcome measures

Outcome measures
Measure	AZD4547 n=36 Participants 80mg BD 2 weeks on/1 week off	Paclitaxel n=26 Participants 80mg / m\^2
Percentage Change From Baseline at Week 8 in Target Lesion Size	28.4 Percentage change Standard Deviation 44.4	-1.1 Percentage change Standard Deviation 36.18

SECONDARY outcome

Timeframe: Week 8 (±1 week)

Population: Full analysis set - all treated patients

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

Outcome measures

Outcome measures
Measure	AZD4547 n=41 Participants 80mg BD 2 weeks on/1 week off	Paclitaxel n=30 Participants 80mg / m\^2
Percentage of Patients Without Progressive Disease at 8 Weeks	24.4 Percentage of patients	53.3 Percentage of patients

Adverse Events

AZD4547

Serious events: 8 serious events

Other events: 39 other events

Deaths: 0 deaths

Paclitaxel

Serious events: 6 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Donal Landers

Astrazeneca

Phone: +44 1625 231890

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	AZD4547 n=40 participants at risk 80mg BD 2 weeks on/1 week off	Paclitaxel n=27 participants at risk 80mg / m\^2
Infections and infestations Biliary tract infection	0.00% 0/40 • 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.	3.7% 1/27 • Number of events 1 • 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.
Blood and lymphatic system disorders Anaemia	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Vascular disorders Arterial disorder	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/40 • 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.	3.7% 1/27 • Number of events 1 • 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.
Gastrointestinal disorders Dyspepsia	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Hepatobiliary disorders Bile duct obstruction	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
General disorders Asthenia	0.00% 0/40 • 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.	3.7% 1/27 • Number of events 1 • 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.
Investigations Blood bilirubin increased	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Gastrointestinal disorders Dysphagia	0.00% 0/40 • 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.	3.7% 1/27 • Number of events 1 • 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.
Gastrointestinal disorders Intestinal haemorrhage	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Gastrointestinal disorders Obstruction gastric	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Gastrointestinal disorders Stomatitis	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Gastrointestinal disorders Vomiting	2.5% 1/40 • Number of events 1 • 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.	7.4% 2/27 • Number of events 2 • 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.
Infections and infestations Lower respiratory tract infection	0.00% 0/40 • 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.	3.7% 1/27 • Number of events 1 • 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.
Infections and infestations Pneumonia	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Infections and infestations Urinary tract infection	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.
Investigations Transaminases increases	2.5% 1/40 • Number of events 1 • 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.	0.00% 0/27 • 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.