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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Olaparib
* Drug: Paclitaxel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olaparib+ paclitaxel<br>olaparib + paclitaxel | Drug: Olaparib<br>* 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.<br>Drug: Paclitaxel<br>* IV infusion over 1 hour at 80 mg/m2 weekly on days 1, 8 and 15 of a 28 days schedule.<br>|
| Placebo Comparator: Placebo+paclitaxel<br>placebo+ paclitaxel | Drug: Paclitaxel<br>* IV infusion over 1 hour at 80 mg/m2 weekly on days 1, 8 and 15 of a 28 days schedule.<br>Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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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 |