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Efficacy and Safety Study of Olaparib in Combination With Paclitaxel to Treat Advanced Gastric Cancer.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01924533
Recruitment Status : Active, not recruiting
First Posted : August 16, 2013
Results First Posted : November 7, 2018
Last Update Posted : June 30, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE August 14, 2013
First Posted Date  ICMJE August 16, 2013
Results First Submitted Date  ICMJE February 27, 2017
Results First Posted Date  ICMJE November 7, 2018
Last Update Posted Date June 30, 2021
Actual Study Start Date  ICMJE September 3, 2013
Actual Primary Completion Date April 4, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 5, 2018)
Overall Survival [ Time Frame: Survival contact from the date of randomization and then every 8 weeks following objective disease progression and in the 7 days following OS Data Cut off (DCO); Time point(s) at which outcome measure is assessed up to 4 years ]
Time from the date of randomization until death due to any cause
Original Primary Outcome Measures  ICMJE
 (submitted: August 14, 2013)
Overall surivival [ Time Frame: Survival contact from the date of randomization and then every 8 weeks following objective disease progression and in the 7 days following OS Data Cut off (DCO); Time point(s) at which outcome measure is assessed up to 4 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2018)
  • Progression-Free Survival (PFS) [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]
    Time from randomization until the date of objective radiological disease progression according to RECIST (v1.1) or death by any cause in the absence of progression. Objective progression is defined as at least a 20% increase in the sum of the diameters of the target lesions (compared to previous minimum sum) or an overall non-target lesion assessment of progression or a new lesion.
  • Number of Patients With Objective Response. [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]
    Number of patients with objective response. Per RECIST 1.1, complete response (CR) is disappearance of all target lesions since baseline; partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Overall Response = CR + PR.
  • Number of Patients Objective Response [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]
    Number of patients with objective response. Per RECIST 1.1, complete response (CR) is disappearance of all target lesions since baseline; partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Overall Response = CR + PR.
  • Number of Patients With Deterioration of Health Related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 Item Module (QLQ-C30) Global HRQoL Scale [ Time Frame: Pre-treatment , Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years ]
    Number of patients with a clinically important deterioration in the global HRQoL score or death by any cause in the absence of a clincially meaningful symptom deterioration
  • Time to Response [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]
    Time from randomization to the first onset of a confirmed objective tumour response
  • Duration of Response [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]
    Time from the first documentation of CR/PR until the date of progression, or the last evaluable RECIST assessment for patients taht do not progress or progress after two or more missed visits
Original Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2013)
  • Progression-Free Survival (PFS) including the time to response and the duration of response assessed by RECIST 1.1 [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]
  • Objective Response Rate (ORR) including the time to response and the duration of the response assessed by RECIST 1.1 [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]
  • To investigate plasma exposure to olaparib in a subset of olaparib dosed patients in the presence of paclitaxel and assess the impact of previous gastric surgery on that exposure [ Time Frame: Blood samples (2 mL) for determination of olaparib in plasma will be taken at the times on pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours after first dose of study ]
  • Ataxia-Telangiectasia Mutation (ATM) and Meiotic recombination 11 homolog (MRE-11) tumour status [ Time Frame: Samples will be taken on Day 1 ]
    A recent study showing low concordance between the ATM status of metastases and primary tumours has been reported, therefore in order to further understand the variability of ATM status in the primary tumour versus metastatic tumour, it is highly recommended that in addition to the mandatory archival tumour samples, fixed tumour samples are also submitted from both primary and metastatic lesions. prior to start of dosing
  • Time to deterioration of HRQoL as assessed by the EORTC QLQ-C30 global HRQoL scale [ Time Frame: Day 1, Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years ]
  • Assessment of Adverse events (AEs) [ Time Frame: Assessed up to 3 years ]
  • Assessments of physical examination, vital signs (including blood pressure (BP) and pulse) [ Time Frame: Assessed up to 3 years ]
  • Assessment of electrocardiogram (ECG)(if clinically indicated) [ Time Frame: Assessed up to 3 years ]
  • Assessment of aboratory findings including clinical chemistry, haematology and urinalysis (if clinically indicated) [ Time Frame: Assessed up to 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of Olaparib in Combination With Paclitaxel to Treat Advanced Gastric Cancer.
Official Title  ICMJE A Randomized, Double-blinded, Placebo Controlled, Multicentre Phase III Study to Assess the Efficacy and Safety of Olaparib (AZD2281) in Combination With Paclitaxel, Compared to Placebo in Combination With Paclitaxel, in Asian Patients With Advanced Gastric Cancer (Including the Gastro-oesophageal Junction) Who Have Progressed Following First Line Therapy
Brief Summary This study is a phase III, multi-centre study of olaparib in combination with paclitaxel, compared with placebo in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy. Patients will be from China, Japan , Korea and Taiwan.
Detailed Description A randomized, double-blinded, multicentre phase III study to access the efficacy and safety of olaparib in combination with paclitaxel, compared with placebo in combination with paclitaxel in Asian patients with advanced gastric cancer (including gastro-oesophageal junction) who have progressed following first line therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Gastric Cancer
Intervention  ICMJE
  • Drug: Olaparib
    Tablets-at a dose of 100mg orally twice daily, throughout each cycle (28 days); Once paclitaxel dosing is stopped, the planned monotherapy olaparib dose will be 300mg twice daily.
  • Drug: Paclitaxel
    IV infusion over 1 hour at 80 mg/m2 weekly on days 1, 8 and 15 of a 28 days schedule.
  • Drug: Placebo
    Tablets-at a dose of 100mg orally twice daily, throughout each cycle (28 days); Once paclitaxel dosing is stopped, the planned monotherapy placebo dose will be 300mg twice daily.
Study Arms  ICMJE
  • Experimental: Olaparib+ paclitaxel
    olaparib + paclitaxel
    Interventions:
    • Drug: Olaparib
    • Drug: Paclitaxel
  • Placebo Comparator: Placebo+paclitaxel
    placebo+ paclitaxel
    Interventions:
    • Drug: Paclitaxel
    • Drug: Placebo
Publications * Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. doi: 10.1016/S1470-2045(17)30682-4. Epub 2017 Nov 2.

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 5, 2018)
525
Original Estimated Enrollment  ICMJE
 (submitted: August 14, 2013)
500
Estimated Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date April 4, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Advanced gastric cancer (including GEJ) that has progressed following first-line therapy.
  • Patients must be ≥18 years of age. Age ≥20 if Japanese
  • Provision of tumour sample (from either a resection or biopsy).
  • At least one lesion (measurable and/or non-measurable) that can be accurately assessed by imaging (CT/MRI) at baseline and following up visits.

Exclusion Criteria:

  • More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
  • Any previous treatment with a Polyadenosine 5'-diphosphoribose [poly-(ADP-ribose)] polymerisation (PARP) inhibitor, including olaparib.
  • Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥5 years.
  • Human Epidermalgrowth Factor Receptor-2 (HER2) positive patients.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 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 China,   Japan,   Korea, Republic of,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01924533
Other Study ID Numbers  ICMJE D081BC00004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yung-Jue Bang, MD Seoul National University, College of Medicine and Cancer Research Institute, Republic of Korea
PRS Account AstraZeneca
Verification Date June 2021

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