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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

Tracking Information
First Submitted Date  ICMJE September 16, 2011
First Posted Date  ICMJE October 24, 2011
Results First Submitted Date  ICMJE February 11, 2016
Results First Posted Date  ICMJE March 7, 2017
Last Update Posted Date March 7, 2017
Study Start Date  ICMJE November 2011
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2017)
Median Progression Free Survival [ Time Frame: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week) ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: October 20, 2011)
Assessment of relative efficacy of AZD4547 compared with paclitaxel by comparison of the change in tumour size at 8 weeks (as measured by RECIST) in all patients and also in patients with FGFR2 amplified tumours (FISH 6) alone [ Time Frame: Based on RECIST measurements taken at baseline and at week 8. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2017)
  • Overall Survival : Number of Patients Who Had Died at DCO (Data Cut Off) [ Time Frame: Tumour size assessed at week 8 (±1 week) and then every 8 weeks (±1 week) ]
  • Objective Response Rate [ Time Frame: Week 8 (±1 week) and then every 8 weeks (±1 week) ]
    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.
  • Percentage Change From Baseline at Week 8 in Target Lesion Size [ Time Frame: Baseline, Week 8 (±1 week) ]
    A negative change denotes a reduction in target lesion size. Percentage change from baseline in tumour size at 8 weeks in target lesion size.
  • Percentage of Patients Without Progressive Disease at 8 Weeks [ Time Frame: Week 8 (±1 week) ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2011)
  • Relative efficacy of AZD4547 compared with paclitaxel by assessment of progression free survival (measured by RECIST 1.1 or death), in all randomized patients and also in patients with FGFR2 amplified tumours (FISH 6) alone [ Time Frame: RECIST assessments will be performed at baseline and every 8 weeks until progression. ]
  • Efficacy of AZD4547 vs paclitaxel by assessment of objective response rate (% of Patients with Complete or Partial Response prior to progression as measured by RECIST 1.1) in randomized patients and patients with FGFR2 amplified tumours (FISH 6) alone [ Time Frame: RECIST assessments will be performed at baseline and every 8 weeks until progression. ]
  • Assess the efficacy of AZD4547 and paclitaxel by assessment of the percentage of patients without progressive disease (as measured by RECIST 1.1) at 8 weeks [ Time Frame: RECIST assessment to be performed at baseline and at week 8. ]
  • Investigate pharmacokinetics of AZD4547 in advanced gastric cancer patient population. [ Time Frame: Plasma AZD4547 measured as follows -Cycle 1 - Day 8 (pre), Day 15 (pre, 0.5-2, 5-6, 8-12 hrs) Cycle 2 - Day 1 (pre), Day 15 (pre, 0.5-2, 5-6, 8-12 hrs) ]
  • Investigate possible relationships between plasma AZD4547 and levels of phosphate [ Time Frame: Biomarker samples taken during screening, Cycle 1 Day 8 and Day 15, Cycle 3 Day 1 and Day 1 of each subsequent cycle. ]
  • Investigate possible relationships between plasma AZD4547 and levels of bFGF [ Time Frame: Biomarker samples taken during screening, Cycle 1 Day 8 and Day 15, Cycle 3 Day 1 and Day 1 of each subsequent cycle. ]
  • Investigate possible relationships between plasma AZD4547 and levels of FGF23 [ Time Frame: Biomarker samples taken during screening, Cycle 1 Day 8 and Day 15, Cycle 3 Day 1 and Day 1 of each subsequent cycle. ]
  • Safety and tolerability of AZD4547 versus paclitaxel in terms of adverse events [ Time Frame: Base line up to 28 days after study drug discontinuation. ]
    Adverse events
  • Safety and tolerability of AZD4547 versus paclitaxel by assessing changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis) [ Time Frame: Base line up tu 28 days after study drug discontinuation. ]
    Laboratory data
  • Safety and tolerability of AZD4547 versus paclitaxel in terms of changes from baseline in vital signs [ Time Frame: Base line up to 28 days after study drug discontinuation. ]
    Vital signs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of AZD4547 Versus Paclitaxel in Patients With Advanced Gastric or Gastro-oesophageal Cancer
Official Title  ICMJE 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.
Brief 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 FGFR2 polysomy or gene amplification.
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). Patients were to be assigned to strata by FGFR2 status of: polysomy, low or high gene amplification.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Gastro-oesophageal Junction Cancer
  • Gastric Cancer
Intervention  ICMJE
  • Drug: AZD4547
    Tablets taken, oral, twice daily, commencing with a 2 week on AZD4547, 1 week off AZD4547 schedule.
  • Drug: paclitaxel
    Infusion administered once a week, 3 weeks on and 1 week off
Study Arms  ICMJE
  • Experimental: AZD4547
    AZD4547 taken orally in tablet formation, 80mg b.d., in a 2 week on, 1 week off schedule
    Intervention: Drug: AZD4547
  • 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)
    Intervention: Drug: paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 11, 2014)
960
Original Estimated Enrollment  ICMJE
 (submitted: October 20, 2011)
55
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Bulgaria,   Canada,   Czech Republic,   France,   Germany,   Hungary,   India,   Italy,   Japan,   Korea, Republic of,   Romania,   Spain,   Taiwan,   Ukraine,   United Kingdom
Removed Location Countries Brazil,   Russian Federation
 
Administrative Information
NCT Number  ICMJE NCT01457846
Other Study ID Numbers  ICMJE D2610C00004
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account AstraZeneca
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP