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

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Olaparib; Drug: Paclitaxel; Drug: Placebo

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
• Enrollment (Actual): 525
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Research Site
  • Beijing, China, 100021
    • Research Site
  • Beijing, China, 100071
    • Research Site
  • Bengbu, China, 233060
    • Research Site
  • Changchun, China, 130000
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Changsha, China, 410011
    • Research Site
  • Changsha, China, 410005
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chengdu, China, 610083
    • Research Site
  • Fuzhou, China, 350014
    • Research Site
  • Guangzhou, China, 510060
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Hangzhou, China, 310016
    • Research Site
  • Harbin, China, 150081
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Nanjing, China, 210002
    • Research Site
  • Nanjing, China, 210009
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 200092
    • Research Site
  • Urumqi, China, 830000
    • Research Site
  • Wanzhou, China, 404000
    • Research Site
  • Wuhan, China, 430030
    • Research Site
  • Yangzhou, China, 225001
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site
• Japan
  • Chiba-shi, Japan, 260-8717
    • Research Site
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Fukuoka-shi, Japan, 811-1395
    • Research Site
  • Kasama-shi, Japan, 309-1793
    • Research Site
  • Kawasaki-shi, Japan, 216-8511
    • Research Site
  • Kitaadachi-gun, Japan, 362-0806
    • Research Site
  • Koto-ku, Japan, 135-8550
    • Research Site
  • Matsuyama-shi, Japan, 791-0280
    • Research Site
  • Nagoya-shi, Japan, 464-8681
    • Research Site
  • Sapporo-shi, Japan, 003-0804
    • Research Site
  • Sapporo-shi, Japan, 060-8648
    • Research Site
  • Takatsuki-shi, Japan, 569-8686
    • Research Site
  • Utsunomiya-shi, Japan, 320-0834
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Research Site
• Korea, Republic of
  • Anyang-si, Korea, Republic of, 431-070
    • Research Site
  • Daegu, Korea, Republic of, 42415
    • Research Site
  • Hwasun-gun, Korea, Republic of, 58128
    • Research Site
  • Jeonju-si, Korea, Republic of, 561-712
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 156-707
    • Research Site
  • Seoul, Korea, Republic of, 02841
    • Research Site
  • Seoul, Korea, Republic of, 06273
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Research Site
  • Seoul, Korea, Republic of, 6351
    • Research Site
• Taiwan
  • Kaohsiung Hsien, Taiwan, 83342
    • Research Site
  • Taichung, Taiwan
    • Research Site
  • Tainan, Taiwan, 704
    • Research Site
  • Taipei, Taiwan, 11217
    • Research Site
  • Taoyuan, Taiwan, 333
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olaparib+ paclitaxel; olaparib + paclitaxel	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.
Placebo Comparator: Placebo+paclitaxel; placebo+ paclitaxel	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from the date of randomization until death due to any cause	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	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.	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.	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.	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 Objective Response	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.	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 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	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	Pre-treatment , Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years
Time to Response	Time from randomization to the first onset of a confirmed objective tumour response	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
Duration of Response	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	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

Collaborators and Investigators

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

Publications and helpful links

General 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.

Helpful Links

• Study protocol-redacted
• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2013
• Primary Completion (Actual): April 4, 2016
• Study Completion (Actual): March 27, 2023

Study Registration Dates

• First Submitted: August 14, 2013
• First Submitted That Met QC Criteria: August 14, 2013
• First Posted (Estimated): August 16, 2013

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Poly(ADP-ribose) Polymerase Inhibitors; Paclitaxel; Olaparib
• Other Study ID Numbers: D081BC00004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing 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
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP