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

• ClinicalTrials.gov Identifier: NCT01924533
• Recruitment Status: Completed
• First Posted: August 16, 2013
• Results First Posted: November 7, 2018
• Last Update Posted: March 22, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: August 14, 2013
• First Posted Date: August 16, 2013
• Results First Submitted Date: February 27, 2017
• Results First Posted Date: November 7, 2018
• Last Update Posted Date: March 22, 2024
• Actual Study Start Date: September 3, 2013
• Actual Primary Completion Date: April 4, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: Efficacy and Safety Study of Olaparib in Combination With Paclitaxel to Treat Advanced Gastric Cancer.
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Gastric Cancer

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 5, 2018): 525
• Original Estimated Enrollment (submitted: August 14, 2013): 500
• Actual Study Completion Date: March 27, 2023
• Actual Primary Completion Date: April 4, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Japan, Korea, Republic of, Taiwan

Administrative Information

• NCT Number: NCT01924533
• Other Study ID Numbers: D081BC00004
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• 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

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Yung-Jue Bang, MD; Seoul National University, College of Medicine and Cancer Research Institute, Republic of Korea

• PRS Account: AstraZeneca
• Verification Date: March 2024