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

Purpose

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.

Condition	Intervention	Phase
Gastro-oesophageal Junction Cancer Gastric Cancer	Drug: AZD4547 Drug: paclitaxel	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Stomach Cancer

Drug Information available for: Paclitaxel

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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 [ Time Frame: RECIST assessments will be performed at baseline and every 8 weeks until progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Time Frame: Survival contacts, every 3 months after discontinuation of study drug until maturity of the OS endpoint ] [ Designated as safety issue: No ]
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 [ Time Frame: RECIST, baseline and at week 8 ] [ Designated as safety issue: No ]
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 [ Time Frame: RECIST, baseline and every 8 weeks until progression ] [ Designated as safety issue: No ]
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 [ Time Frame: RECIST, baseline and at week 8 ] [ Designated as safety issue: No ]
Safety and tolerability of AZD4547 vs paclitaxel by assessing changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis), vital signs & adverse events [ Time Frame: Lab data, vital signs & adverse events - screening to 28 days after study drug disc ] [ Designated as safety issue: Yes ]
Investigate pharmacokinetics of AZD4547 in patients receiving AZD4547. [ Time Frame: (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 ] [ Designated as safety issue: Yes ]
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
Investigate possible relationships between plasma AZD4547 and levels of bFGF, FGF23 & phosphate. [ Time Frame: screening, Cycle 1 Day 8 Day 15, Cycle 3 Day 1, Day 1 of each subsequent cycle ] [ Designated as safety issue: No ]
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 [ Time Frame: EORTC QLQ-C30, QLQ-STO22 once every 3 weeks until the end of the follow up period ] [ Designated as safety issue: No ]
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 [ Time Frame: EORTC QLQ-C30, QLQ-STO22 once every 3 weeks until the end of the follow up period ] [ Designated as safety issue: No ]
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 [ Time Frame: WHO performance status at all visits ] [ Designated as safety issue: No ]

Estimated Enrollment:	240
Study Start Date:	November 2011
Estimated Study Completion Date:	May 2016
Estimated Primary Completion Date:	May 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AZD4547 AZD4547 taken orally in tablet formation, 80mg b.d., in a 2 week on, 1 week off schedule	Drug: AZD4547 Tablets taken, oral, twice daily, commencing with a 2 week on AZD4547, 1 week off AZD4547 schedule.
Active Comparator: Paclitaxel 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)	Drug: paclitaxel Infusion administered once a week, 3 weeks on and 1 week off

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)

Eligibility

Ages Eligible for Study:	25 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01457846

Contacts

Contact: AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Show 85 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Paul Stockman, MD PHD	AstraZeneca
Principal Investigator:	Eric Van Cutsem, MD PHD	University Hospital, Gasthuisberg
Principal Investigator:	Yung-Jue Bang, MD, PHD	Seoul National University Hospital

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01457846 History of Changes
Other Study ID Numbers:	D2610C00004
Study First Received:	September 16, 2011
Last Updated:	June 12, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) South Korea: Korea Food and Drug Administration (KFDA) Taiwan : Food and Drug Administration Belgium: Federal Agency for Medicinal Products and Health Products India: Drugs Controller General of India Italy: National Institute of Health Spain: Agencia Española de Medicamentos y Productos Sanitarios Czech Republic: State Institute for Drug Control Ukraine: State Pharmacological Center - Ministry of Health Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy Romania: National Medicines Agency Russia: Ministry of Health of the Russian Federation Japan: Ministry of Health, Labor and Welfare Bulgaria: Bulgarian Drug Agency Canada: Health Canada Brazil: National Health Surveillance Agency

Keywords provided by AstraZeneca:

gastro-oesphageal junction cancer
gastric cancer
lower third oesophageal cancer

polysomy
amplification
FGFR

Additional relevant MeSH terms:

Adenocarcinoma
Esophageal Diseases
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms

Neoplasms by Site
Stomach Diseases
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013

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