Gastric Cancer
Conditions
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.
Interventions
DRUGOlaparib
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.
DRUGPaclitaxel
IV infusion over 1 hour at 80 mg/m2 weekly on days 1, 8 and 15 of a 28 days schedule.
DRUGPlacebo
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.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Objective 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 | 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. |
| Time to 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 | Time from randomization to the first onset of a confirmed objective tumour response |
| Progression-Free Survival (PFS) | 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 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 | 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 |
| Duration of 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 | 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 |
| Number of Patients Objective 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 | 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. |
Countries
China, Japan, South Korea, Taiwan
Participant flow
Pre-assignment details
The number of participants in the participant flow (525) includes all participants who were eligible and assigiend to each treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m\^2 | 263 |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 Placebo tablets bd + Paclitaxel 80 mg/m\^2 | 262 |
| Total | 525 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 181 | 200 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other Eligibility criteria | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Total | Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 |
|---|---|---|---|
| Age, Continuous | 60.9 Years STANDARD_DEVIATION 9.9 | 58.9 Years STANDARD_DEVIATION 11.18 | 57.1 Years STANDARD_DEVIATION 11.9 |
| Age, Customized >=18 - <50 | 7 Participants | 19 Participants | 12 Participants |
| Age, Customized >=50 - <65 | 128 Participants | 243 Participants | 22 Participants |
| Age, Customized >=65 | 15 Participants | 150 Participants | 14 Participants |
| ATM Status Negative | 46 Participants | 94 Participants | 48 Participants |
| ATM Status Positive | 196 Participants | 396 Participants | 200 Participants |
| ATM Status Unknown | 20 Participants | 35 Participants | 15 Participants |
| Gastrectomy Status Full | 13 Participants | 26 Participants | 13 Participants |
| Gastrectomy Status None | 21 Participants | 37 Participants | 16 Participants |
| Gastrectomy Status Partial | 72 Participants | 149 Participants | 19 Participants |
| Race/Ethnicity, Customized Asian | 262 Participants | 525 Participants | 263 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 46 Participants | 94 Participants | 48 Participants |
| Race/Ethnicity, Customized Not Hispanic Or Latino | 262 Participants | 525 Participants | 263 Participants |
| Sex: Female, Male Female | 77 Participants | 166 Participants | 89 Participants |
| Sex: Female, Male Male | 185 Participants | 359 Participants | 174 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 181 / 263 | 200 / 262 |
| other Total, other adverse events | 257 / 262 | 253 / 259 |
| serious Total, serious adverse events | 92 / 262 | 65 / 259 |
Outcome results
Primary
Overall Survival
Time from the date of randomization until death due to any cause
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
Population: Full analysis set population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Overall Survival | 82 participants |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Overall Survival | 62 participants |
p-value: 0.026297.5% CI: [0.63, 1]Cox proportional hazards model
Primary
Overall Survival
Time from the date of randomization until death due to any cause
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
Population: Full analysis set - ATM negative population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Overall Survival | 19 participants |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Overall Survival | 11 participants |
p-value: 0.245897.5% CI: [0.4, 1.34]Cox proportional hazards model
Secondary
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
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
Population: Patients with objective response in full analysis set ATM negative population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Duration of Response | 171.0 days |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Duration of Response | 108.0 days |
Secondary
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
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
Population: Patients with objective response in full analysis set population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Duration of Response | 166.0 days |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Duration of Response | 64.0 days |
Secondary
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.
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
Population: Full analysis set - ATM negative population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Number of Patients Objective Response | 12 participants |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Number of Patients Objective Response | 5 participants |
p-value: 0.030997.5% CI: [0.95, 23.23]Regression, Logistic
Secondary
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
Time frame: Pre-treatment , Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years
Population: Patients whose baseline HRQoL score \>=10 in full analysis set population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | 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 | 160 participants |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | 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 | 177 participants |
p-value: 0.071697.5% CI: [0.64, 1.05]Cox proportional hazards model
Secondary
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
Time frame: Pre-treatment , Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years
Population: Patients whose baseline HRQoL score \>=10 in full analysis set ATM negative population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | 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 | 29 participants |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | 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 | 33 participants |
p-value: 0.092797.5% CI: [0.34, 1.16]Cox proportional hazards model
Secondary
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.
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
Population: Full analysis set population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Number of Patients With Objective Response. | 44 participants |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Number of Patients With Objective Response. | 28 participants |
p-value: 0.054897.5% CI: [0.92, 3.17]Regression, Logistic
Secondary
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.
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
Population: FAS analysis set - ATM negative population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Progression-Free Survival (PFS) | 11 participants |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Progression-Free Survival (PFS) | 7 participants |
p-value: 0.219997.5% CI: [0.42, 1.29]Cox proportional hazards model
Secondary
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.
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
Population: FAS analysis set population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Progression-Free Survival (PFS) | 47 participants |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Progression-Free Survival (PFS) | 29 participants |
p-value: 0.064597.5% CI: [0.67, 1.04]Cox proportional hazards model
Secondary
Time to Response
Time from randomization to the first onset of a confirmed objective tumour 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
Population: Patients with objective response in full analysis set population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Time to Response | 57.0 days |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Time to Response | 57.0 days |
Secondary
Time to Response
Time from randomization to the first onset of a confirmed objective tumour 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
Population: Patients with objective response in full analysis set ATM negative population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 100 mg Tablets bd + Paclitaxel 80 mg/m^2 | Time to Response | 57.5 days |
| Placebo Tablets bd + Paclitaxel 80 mg/m^2 | Time to Response | 57.0 days |