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

Gastric Cancer Clinical Trial

— SHINE  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01457846
• Other study ID #: D2610C00004
• Status: Completed
• Phase: Phase 2
• First received: September 16, 2011
• Last updated: April 15, 2015
• Start date: November 2011
• Est. completion date: February 2015

Study information

• Verified date: April 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)South Korea: Korea Food and Drug Administration (KFDA)Taiwan : Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsIndia: Drugs Controller General of IndiaItaly: National Institute of HealthSpain: Agencia Española de Medicamentos y Productos SanitariosCzech Republic: State Institute for Drug ControlUkraine: State Pharmacological Center - Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyRomania: National Medicines AgencyRussia: Ministry of Health of the Russian FederationJapan: Ministry of Health, Labor and WelfareBulgaria: Bulgarian Drug AgencyCanada: Health CanadaBrazil: National Health Surveillance Agency
• Study type: Interventional

Clinical 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 increased number of FGFR2 gene.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 960
• Est. completion date: February 2015
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastric Cancer
• Gastro-oesophageal Junction Cancer
• Stomach Neoplasms

Intervention

Drug:
• AZD4547
Tablets taken, oral, twice daily, commencing with a 2 week on AZD4547, 1 week off AZD4547 schedule.
• paclitaxel
Infusion administered once a week, 3 weeks on and 1 week off

Locations

Country	Name	City	State
Belgium	Research Site	Brussels (Anderlecht)
Belgium	Research Site	Brussels (Woluwé-St-Lambert)
Belgium	Research Site	Leuven
Belgium	Research Site	Liege
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Vratza
Canada	Research Site	Fredericton	New Brunswick
Canada	Research Site	Toronto	Ontario
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Praha 2
France	Research Site	Saint Cloud
France	Research Site	Villejuif Cedex
Germany	Research Site	Hamburg
Germany	Research Site	Mainz
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Nyíregyháza
India	Research Site	Bangalore
India	Research Site	Chennai
India	Research Site	Hyderabad
India	Research Site	Nagpur
India	Research Site	Pune
India	Research Site	Vellore
Italy	Research Site	Ancona
Italy	Research Site	Milano
Italy	Research Site	Pisa
Italy	Research Site	Roma
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Koto-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Takatsuki-shi
Korea, Republic of	Research Site	Anyang-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Hwasun-gun
Korea, Republic of	Research Site	Jeonju-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Romania	Research Site	Brasov
Romania	Research Site	Cluj Napoca
Spain	Research Site	A Coruña
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Oviedo
Spain	Research Site	Santander
Spain	Research Site	Sevilla
Taiwan	Research Site	Keelung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Lviv
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Canada,  Czech Republic,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Romania,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigate the efficacy of AZD4547 vs paclitaxel by assessment of Progression-Free Survival in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone		RECIST assessments will be performed at baseline and every 8 weeks until progression	No
Secondary	Investigate the efficacy of AZD4547 vs paclitaxel by comparison of Overall Survival in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone		Survival contacts, every 3 months after discontinuation of study drug until maturity of the OS endpoint	No
Secondary	Investigate the efficacy of AZD4547 vs. paclitaxel by comparison of the change in tumour size at 8 weeks in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone		RECIST, baseline and at week 8	No
Secondary	Efficacy of AZD4547 vs paclitaxel by comparison of objective response rate and duration of response in: all randomised patients; patients with tumours that have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone		RECIST, baseline and every 8 weeks until progression	No
Secondary	Efficacy of AZD4547 vs paclitaxel by comparison of % of patients without progression disease at 8 weeks in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone		RECIST, baseline and at week 8	No
Secondary	Safety and tolerability of AZD4547 vs paclitaxel by assessing changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis), vital signs & adverse events		Lab data, vital signs & adverse events - screening to 28 days after study drug disc	Yes
Secondary	Investigate pharmacokinetics of AZD4547 in patients receiving AZD4547.	AZD4547 (pre-interim): C1 - D7 pre, D14 (0,0.5-2, 5-6, 8-12 hrs);C2 - D1 pre, D14 (0, 0.5-2, 5-6, 8-12 hrs);(Post interim):C1 - D7 pre, D14 (0, 3hr);C2 - D1 (pre), D14 (pre, 3hr); All, 0-48hr post last dose	(pre-interim): C1 - D7 pre, D14 (0,0.5-2, 5-6, 8-12 hrs);C2 - D1 pre, D14 (0, 0.5-2, 5-6, 8-12 hrs);(Post interim):C1 - D7 pre, D14 (0, 3hr);C2 - D1 (pre), D14 (pre, 3hr); All, 0-48hr post last dose	Yes
Secondary	Investigate possible relationships between plasma AZD4547 and levels of bFGF, FGF23 & phosphate.		screening, Cycle 1 Day 8 Day 15, Cycle 3 Day 1, Day 1 of each subsequent cycle	No
Secondary	Disease-related symptom changes & time to symptom progression in patients receiving AZD4547/paclitaxel in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone		EORTC QLQ-C30, QLQ-STO22 once every 3 weeks until the end of the follow up period	No
Secondary	Changes in and time to deterioration of Health Related Quality of Life in patients receiving AZD4547/paclitaxel in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone		EORTC QLQ-C30, QLQ-STO22 once every 3 weeks until the end of the follow up period	No
Secondary	Changes in, and time to deterioration of, WHO performance status in patients receiving AZD4547/paclitaxel in: all randomised patients; patients with tumours have FGFR2 amplification & patients with tumours have high FGFR2 amplification alone		WHO performance status at all visits	No