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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01457846
First received: September 16, 2011
Last updated: March 11, 2014
Last verified: March 2014
  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:


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 ]

Enrollment: 960
Study Start Date: November 2011
Estimated Study Completion Date: May 2014
Primary Completion Date: August 2013 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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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: March 11, 2014
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-oesophageal junction cancer
gastric cancer
lower third oesophageal cancer
polysomy
amplification
FGFR

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014