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Efficacy Study of Olaparib With Paclitaxel Versus Paclitaxel in Gastric Cancer Patients

Sponsor
AstraZeneca (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01063517
Collaborator
(none)
124
Enrollment
14
Locations
2
Arms
154.9
Anticipated Duration (Months)
8.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To assess the efficacy of olaparib when given in combination with paclitaxel compared with paclitaxel alone as defined by progression-free survival (PFS), in all patients with recurrent and metastatic gastric cancer who progress following first-line therapy.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
124 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomised, Double Blinded, Multicentre Phase II Study to Assess the Efficacy of Olaparib (AZD2281, KU-0059436) in Combination With Paclitaxel Versus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer Who Progress Following First-line Therapy
Actual Study Start Date :
Feb 2, 2010
Actual Primary Completion Date :
May 11, 2012
Anticipated Study Completion Date :
Dec 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Olaparib + paclitaxel

Drug: olaparib
100mg BID oral tablet continuous

Drug: paclitaxel
iv infusion 80mg/m2 on Day 1, 8 and 15 of a 28 day cycle
Other Names:
  • Taxol

    		•
    Active Comparator: 2

    paclitaxel + placebo

    Drug: paclitaxel
    iv infusion 80mg/m2 on Day 1, 8 and 15 of a 28 day cycle
    Other Names:
  • Taxol

    • Drug: Placebo
    100mg BID oral tablet to match olaparib tablet

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) in the Overall Study Population [Tumour assessments were carried out 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 maximum up to 27 months]

      PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.

    2. Progression Free Survival (PFS) in Patients With Tumours Defined as Homologous Recombination Deficient by Loss of Ataxia-Telangiectasia Mutation (ATM) Protein [ATM Negative Patients] [Tumour assessments are carried out 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 maximum up to 27 months]

      PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.

    Secondary Outcome Measures

    1. Overall Survival (OS) in the Overall Study Population [Survival follow up from randomisation till death of the patient or till end of study in absence of death, assessed maximum up to 27 months]

      Overall survival is defined as the duration from randomisation till death. In absence of death, the time is calculated from randomisation till the date subject last known to be alive.

    2. Overall Survival (OS) in ATM Negative Patients [Survival follow up from randomisation till death of the patient or till end of study in absence of death, assessed maximum up to 27 months]

      Overall survival is defined as the duration from randomisation till death. In absence of death, the time is calculated from randomisation till the date subject last known to be alive.

    3. Objective Response Rate (ORR) in the Overall Study Population [Tumour assessments carried out at baseline, 28 days before randomisation then every 8 weeks until week 40, after week 40 assessments will be carried out every 16 weeks until objective disease progression, assessed maximum up to 27 months]

      Objective response rate is the proportion of patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).

    4. Objective Response Rate (ORR) in the ATM Negative Patients [Tumour assessments carried out at baseline, 28 days before randomisation then every 8 weeks until week 40, after week 40 assessments will be carried out every 16 weeks until objective disease progression, assessed maximum up to 27 months]

      Objective response rate is the proportion of ATM negative patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).

    5. Percentage Change in Tumour Size at Week 8 in the Overall Study Population [Tumour scans done at Baseline and week 8]

      Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)

    6. Percentage Change in Tumour Size at Week 8 in the ATM Negative Patients [Tumour scans done at Baseline and week 8]

      Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)

    7. Time to Deterioration in Global Quality of Life (QoL) Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of Global QoL score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    8. Time to Deterioration in QoL Fatigue Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of fatigue score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    9. Time to Deterioration in QoL Nausea & Vomiting Domain Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of nausea & vomiting domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    10. Time to Deterioration in QoL Pain Domain Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    11. Time to Deterioration in QoL Dysphagia Domain Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of dysphagia domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    12. Time to Deterioration in QoL Eating Restriction Domain Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of eating restriction domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    13. Time to Deterioration in QoL Stomach Pain Domain Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of stomach pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    14. Time to Deterioration in QoL Reflux Domain Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of reflux domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    15. Time to Deterioration in QoL Anxiety Domain Score in the Overall Study Population [Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months]

      Time calculated from randomisation till worsening of anxiety domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Recurrent or metastatic gastric cancer that has progressed following first line-therapy

    • Confirmed ATM protein status by IHC archival tumour sample

    • At least one lesion (measurable and/or non-measurable) that can be accurately assessed by imaging (CT/MRI) at baseline and follow up visits

    Exclusion Criteria:

    • More than one prior chemotherapy regimen for the treatment of gastric cancer in the metastatic or recurrent setting

    • Any previous treatment with a 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Anyang Korea, Republic of 431-070
    2 Research Site Goyang-si Korea, Republic of 410-769
    3 Research Site Jeonju Korea, Republic of 561-712
    4 Research Site Jeonnam Korea, Republic of 519-763
    5 Research Site Seongnam Korea, Republic of 463-707
    6 Research Site Seoul Korea, Republic of 03722
    7 Research Site Seoul Korea, Republic of 110-744
    8 Research Site Seoul Korea, Republic of 134-791
    9 Research Site Seoul Korea, Republic of 135-710
    10 Research Site Seoul Korea, Republic of 135-720
    11 Research Site Seoul Korea, Republic of 136-705
    12 Research Site Seoul Korea, Republic of 137-701
    13 Research Site Seoul Korea, Republic of 138-736
    14 Research Site Taegu Korea, Republic of 705-035

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Study Director: Jane Robertson, BSc, MBCHB, MD, AstraZeneca
    • Principal Investigator: Yung-Jue Bang, MD, Seoul National University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT01063517
    Other Study ID Numbers:
    • D0810C00039
    First Posted:
    Feb 5, 2010
    Last Update Posted:
    Jun 29, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by AstraZeneca
    Poly(ADP ribose)
    polymerase (PARP)
    Gastric cancer
    olaparib
    PARP inhibitor
    ATM AZD2281
    Ku0059436
    Homologous Recombination deficiency (HRD)
    Recurrent gastric cancer
    metastatic gastric cancer
    Additional relevant MeSH terms:
    Stomach Neoplasms
    Paclitaxel
    Olaparib

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at 13 sites in South Korea. Enrolment started in February 2010 and was completed in May 2012. In total 124 patients were randomised in the study (62 in the olaparib+paclitaxel arm and 62 in the placebo+paclitaxel arm).
    Pre-assignment Detail Patients of either sex, age more than 17 years with recurrent or metastatic gastric cancer that had progressed following first line therapy, a confirmed Ataxia Telangiectasia Mutation (ATM) status, Eastern Co operative Oncology Group (ECOG) performance status ≤2, normal organ and bone marrow function, and life expectancy ≥16 weeks.
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Period Title: Overall Study
    STARTED 62 62
    Received Randomised Treatment 61 62
    COMPLETED 4 2
    NOT COMPLETED 58 60

    Baseline Characteristics

    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel Total
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy. Total of all reporting groups
    Overall Participants 62 62 124
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.0
    (11.61)
    59.4
    (11.98)
    59.2
    (11.75)
    Age, Customized (Number) [Number]
    < 50 years
    13
    21%
    10
    16.1%
    23
    18.5%
    >=50 to <65 years
    22
    35.5%
    30
    48.4%
    52
    41.9%
    >= 65 years
    27
    43.5%
    22
    35.5%
    49
    39.5%
    Sex: Female, Male (Count of Participants)
    Female
    13
    21%
    18
    29%
    31
    25%
    Male
    49
    79%
    44
    71%
    93
    75%
    Race/Ethnicity, Customized (Number) [Number]
    Asian
    62
    100%
    62
    100%
    124
    100%
    Other
    0
    0%
    0
    0%
    0
    0%
    ATM status (Number) [Number]
    Negative
    31
    50%
    32
    51.6%
    63
    50.8%
    Positive
    31
    50%
    30
    48.4%
    61
    49.2%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival (PFS) in the Overall Study Population
    Description PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.
    Time Frame Tumour assessments were carried out 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 maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Full analysis set including all randomised patients
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 62 62
    Median (Inter-Quartile Range) [months]
    3.91
    3.55
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Olaparib+Paclitaxel, Placebo+Paclitaxel
    Comments The analysis was performed using a Cox proportional hazards model with factors for treatment group, ATM status and gastrectomy (full, partial, none).
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.8
    Confidence Interval (2-Sided) 80%
    0.62 to 1.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments The numerator of the hazard ratio is hazards of progression in olaparib+paclitaxel group and denominator is hazards of progression in placebo+paclitaxel group. Confidence intervals are calculated using the profile-likelihood method.
    2. Primary Outcome
    Title Progression Free Survival (PFS) in Patients With Tumours Defined as Homologous Recombination Deficient by Loss of Ataxia-Telangiectasia Mutation (ATM) Protein [ATM Negative Patients]
    Description PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.
    Time Frame Tumour assessments are carried out 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 maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Full analysis set including randomised ATM negative patients
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 31 32
    Median (Inter-Quartile Range) [months]
    5.29
    3.68
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Olaparib+Paclitaxel, Placebo+Paclitaxel
    Comments The analysis was performed using a Cox proportional hazards model with factors for treatment group and gastrectomy (full, partial, none).
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 80%
    0.51 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments The numerator of the hazard ratio is hazards of progression in olaparib+paclitaxel group and denominator is hazards of progression in placebo+paclitaxel group. Confidence intervals are calculated using the profile-likelihood method.
    3. Secondary Outcome
    Title Overall Survival (OS) in the Overall Study Population
    Description Overall survival is defined as the duration from randomisation till death. In absence of death, the time is calculated from randomisation till the date subject last known to be alive.
    Time Frame Survival follow up from randomisation till death of the patient or till end of study in absence of death, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Full analysis set including all randomised patients
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 62 62
    Median (Inter-Quartile Range) [months]
    13.1
    8.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Olaparib+Paclitaxel, Placebo+Paclitaxel
    Comments The analysis was performed using a Cox proportional hazards model with factors for treatment group, ATM status and gastrectomy (full, partial, none).
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.56
    Confidence Interval (2-Sided) 80%
    0.41 to 0.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments The numerator of the hazard ratio is hazards of death in olaparib+paclitaxel group and denominator is hazards of death in placebo+paclitaxel group. Confidence intervals are calculated using the profile-likelihood method.
    4. Secondary Outcome
    Title Overall Survival (OS) in ATM Negative Patients
    Description Overall survival is defined as the duration from randomisation till death. In absence of death, the time is calculated from randomisation till the date subject last known to be alive.
    Time Frame Survival follow up from randomisation till death of the patient or till end of study in absence of death, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Full analysis set including randomised ATM negative patients
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 31 32
    Median (Inter-Quartile Range) [months]
    NA
    8.20
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Olaparib+Paclitaxel, Placebo+Paclitaxel
    Comments The analysis was performed using a Cox proportional hazards model with factors for treatment group and gastrectomy (full, partial, none).
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.35
    Confidence Interval (2-Sided) 80%
    0.22 to 0.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments The numerator of the hazard ratio is hazards of death in olaparib+paclitaxel group and denominator is hazards of death in placebo+paclitaxel group. Confidence intervals are calculated using the profile-likelihood method.
    5. Secondary Outcome
    Title Objective Response Rate (ORR) in the Overall Study Population
    Description Objective response rate is the proportion of patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).
    Time Frame Tumour assessments carried out at baseline, 28 days before randomisation then every 8 weeks until week 40, after week 40 assessments will be carried out every 16 weeks until objective disease progression, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Evaluable for response population - randomised patients having measurable disease at baseline.
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 53 47
    Number [Participants]
    14
    22.6%
    9
    14.5%
    6. Secondary Outcome
    Title Objective Response Rate (ORR) in the ATM Negative Patients
    Description Objective response rate is the proportion of ATM negative patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).
    Time Frame Tumour assessments carried out at baseline, 28 days before randomisation then every 8 weeks until week 40, after week 40 assessments will be carried out every 16 weeks until objective disease progression, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Evaluable for response population ATM negative patients - randomised ATM negative patients having measurable disease at baseline.
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 26 23
    Number [Participants]
    9
    14.5%
    6
    9.7%
    7. Secondary Outcome
    Title Percentage Change in Tumour Size at Week 8 in the Overall Study Population
    Description Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)
    Time Frame Tumour scans done at Baseline and week 8

    Outcome Measure Data

    Analysis Population Description
    Evaluable for response population - randomised patients having measurable disease at baseline.
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 52 47
    Mean (Standard Deviation) [Percent change]
    -5.8
    (29.09)
    2.2
    (35.6)
    8. Secondary Outcome
    Title Percentage Change in Tumour Size at Week 8 in the ATM Negative Patients
    Description Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)
    Time Frame Tumour scans done at Baseline and week 8

    Outcome Measure Data

    Analysis Population Description
    Evaluable for response population ATM negative patients - randomised ATM negative patients having measurable disease at baseline.
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 26 23
    Mean (Standard Deviation) [Percent change]
    -6.9
    (29.31)
    -5.9
    (26.36)
    9. Secondary Outcome
    Title Time to Deterioration in Global Quality of Life (QoL) Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of Global QoL score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having global score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    3.6
    (29.31)
    2.8
    (26.36)
    10. Secondary Outcome
    Title Time to Deterioration in QoL Fatigue Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of fatigue score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having fatigue score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    1.9
    (29.31)
    1.8
    (26.36)
    11. Secondary Outcome
    Title Time to Deterioration in QoL Nausea & Vomiting Domain Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of nausea & vomiting domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having nausea & vomiting domain score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    3.7
    (29.31)
    3.7
    (26.36)
    12. Secondary Outcome
    Title Time to Deterioration in QoL Pain Domain Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having pain domain score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    3.2
    (29.31)
    3.1
    (26.36)
    13. Secondary Outcome
    Title Time to Deterioration in QoL Dysphagia Domain Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of dysphagia domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having dysphagia domain score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    3.7
    (29.31)
    1.9
    (26.36)
    14. Secondary Outcome
    Title Time to Deterioration in QoL Eating Restriction Domain Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of eating restriction domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having eating restriction domain score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    4.6
    (29.31)
    5.1
    (26.36)
    15. Secondary Outcome
    Title Time to Deterioration in QoL Stomach Pain Domain Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of stomach pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having stomach pain domain score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    6.9
    (29.31)
    5.7
    (26.36)
    16. Secondary Outcome
    Title Time to Deterioration in QoL Reflux Domain Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of reflux domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having reflux domain score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    4.3
    (29.31)
    2.8
    (26.36)
    17. Secondary Outcome
    Title Time to Deterioration in QoL Anxiety Domain Score in the Overall Study Population
    Description Time calculated from randomisation till worsening of anxiety domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
    Time Frame Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Randomised patients having anxiety domain score calculated at baseline and at least one post baseline visit
    Arm/Group Title Olaparib+Paclitaxel Placebo+Paclitaxel
    Arm/Group Description Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy. Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
    Measure Participants 61 60
    Median (Inter-Quartile Range) [months]
    2.8
    (29.31)
    1.9
    (26.36)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title OLAPARIB 100MG BD + PACLITAXEL / OLAPARIB 200MG BD PLACEBO 100MG BD + PACLITAXEL / PLACEBO 200MG BD
    Arm/Group Description
    All Cause Mortality
    OLAPARIB 100MG BD + PACLITAXEL / OLAPARIB 200MG BD PLACEBO 100MG BD + PACLITAXEL / PLACEBO 200MG BD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    OLAPARIB 100MG BD + PACLITAXEL / OLAPARIB 200MG BD PLACEBO 100MG BD + PACLITAXEL / PLACEBO 200MG BD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 17/61 (27.9%) 23/62 (37.1%)
    Blood and lymphatic system disorders
    FEBRILE NEUTROPENIA 1/61 (1.6%) 1 0/62 (0%) 0
    NEUTROPENIA 1/61 (1.6%) 1 1/62 (1.6%) 1
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION 1/61 (1.6%) 1 0/62 (0%) 0
    Gastrointestinal disorders
    COLITIS 0/61 (0%) 0 1/62 (1.6%) 1
    DIARRHOEA 1/61 (1.6%) 1 1/62 (1.6%) 1
    GASTROINTESTINAL HAEMORRHAGE 1/61 (1.6%) 1 0/62 (0%) 0
    HAEMATEMESIS 1/61 (1.6%) 1 0/62 (0%) 0
    HAEMORRHOIDS 1/61 (1.6%) 1 0/62 (0%) 0
    OBSTRUCTION GASTRIC 0/61 (0%) 0 1/62 (1.6%) 1
    UPPER GASTROINTESTINAL HAEMORRHAGE 1/61 (1.6%) 1 0/62 (0%) 0
    VOMITING 1/61 (1.6%) 1 0/62 (0%) 0
    General disorders
    ASTHENIA 1/61 (1.6%) 1 2/62 (3.2%) 2
    FATIGUE 2/61 (3.3%) 2 2/62 (3.2%) 2
    PAIN 0/61 (0%) 0 2/62 (3.2%) 2
    PYREXIA 1/61 (1.6%) 1 2/62 (3.2%) 2
    Hepatobiliary disorders
    CHOLANGITIS 0/61 (0%) 0 1/62 (1.6%) 1
    HYPERBILIRUBINAEMIA 0/61 (0%) 0 1/62 (1.6%) 1
    JAUNDICE 0/61 (0%) 0 1/62 (1.6%) 1
    Infections and infestations
    RESPIRATORY TRACT INFECTION 0/61 (0%) 0 1/62 (1.6%) 1
    APPENDICITIS 1/61 (1.6%) 1 0/62 (0%) 0
    CYSTITIS 1/61 (1.6%) 1 0/62 (0%) 0
    ENTEROCOLITIS INFECTIOUS 0/61 (0%) 0 2/62 (3.2%) 2
    HERPES ZOSTER 0/61 (0%) 0 1/62 (1.6%) 1
    LOWER RESPIRATORY TRACT INFECTION 0/61 (0%) 0 1/62 (1.6%) 1
    PNEUMONIA 3/61 (4.9%) 3 6/62 (9.7%) 6
    URINARY TRACT INFECTION 0/61 (0%) 0 1/62 (1.6%) 1
    Injury, poisoning and procedural complications
    LIGAMENT SPRAIN 0/61 (0%) 0 1/62 (1.6%) 1
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED 0/61 (0%) 0 1/62 (1.6%) 1
    Metabolism and nutrition disorders
    DECREASED APPETITE 1/61 (1.6%) 1 2/62 (3.2%) 2
    Nervous system disorders
    CEREBRAL INFARCTION 0/61 (0%) 0 1/62 (1.6%) 1
    CEREBRAL ISCHAEMIA 0/61 (0%) 0 1/62 (1.6%) 1
    SYNCOPE 0/61 (0%) 0 1/62 (1.6%) 1
    Psychiatric disorders
    DELIRIUM 0/61 (0%) 0 1/62 (1.6%) 1
    ALCOHOLISM 1/61 (1.6%) 1 0/62 (0%) 0
    Renal and urinary disorders
    HYDRONEPHROSIS 0/61 (0%) 0 1/62 (1.6%) 1
    Respiratory, thoracic and mediastinal disorders
    PNEUMONITIS 0/61 (0%) 0 1/62 (1.6%) 1
    PULMONARY EMBOLISM 0/61 (0%) 0 1/62 (1.6%) 1
    Vascular disorders
    HYPOTENSION 1/61 (1.6%) 1 0/62 (0%) 0
    THROMBOSIS 0/61 (0%) 0 1/62 (1.6%) 1
    Other (Not Including Serious) Adverse Events
    OLAPARIB 100MG BD + PACLITAXEL / OLAPARIB 200MG BD PLACEBO 100MG BD + PACLITAXEL / PLACEBO 200MG BD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 61/61 (100%) 62/62 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 11/61 (18%) 17 12/62 (19.4%) 23
    FEBRILE NEUTROPENIA 1/61 (1.6%) 1 0/62 (0%) 0
    IRON DEFICIENCY ANAEMIA 1/61 (1.6%) 1 1/62 (1.6%) 1
    LEUKOPENIA 5/61 (8.2%) 5 3/62 (4.8%) 3
    NEUTROPENIA 46/61 (75.4%) 162 40/62 (64.5%) 127
    THROMBOCYTOPENIA 0/61 (0%) 0 3/62 (4.8%) 3
    Cardiac disorders
    ANGINA PECTORIS 1/61 (1.6%) 1 0/62 (0%) 0
    PALPITATIONS 0/61 (0%) 0 1/62 (1.6%) 1
    Ear and labyrinth disorders
    EAR PAIN 1/61 (1.6%) 1 0/62 (0%) 0
    Eye disorders
    CATARACT 1/61 (1.6%) 1 0/62 (0%) 0
    DRY EYE 0/61 (0%) 0 2/62 (3.2%) 2
    EYE PAIN 1/61 (1.6%) 1 1/62 (1.6%) 1
    PTERYGIUM 1/61 (1.6%) 1 0/62 (0%) 0
    VISION BLURRED 1/61 (1.6%) 1 0/62 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT 4/61 (6.6%) 4 0/62 (0%) 0
    ABDOMINAL DISTENSION 4/61 (6.6%) 4 5/62 (8.1%) 5
    ABDOMINAL PAIN 15/61 (24.6%) 18 16/62 (25.8%) 19
    ABDOMINAL PAIN LOWER 1/61 (1.6%) 1 0/62 (0%) 0
    ABDOMINAL PAIN UPPER 8/61 (13.1%) 9 8/62 (12.9%) 10
    ASCITES 0/61 (0%) 0 1/62 (1.6%) 1
    BREATH ODOUR 0/61 (0%) 0 1/62 (1.6%) 1
    CHEILITIS 0/61 (0%) 0 1/62 (1.6%) 1
    DIARRHOEA 20/61 (32.8%) 34 17/62 (27.4%) 28
    DRY MOUTH 0/61 (0%) 0 1/62 (1.6%) 1
    DYSPEPSIA 11/61 (18%) 16 10/62 (16.1%) 13
    EPIGASTRIC DISCOMFORT 1/61 (1.6%) 1 0/62 (0%) 0
    ERUCTATION 1/61 (1.6%) 1 0/62 (0%) 0
    GASTROINTESTINAL HAEMORRHAGE 1/61 (1.6%) 1 2/62 (3.2%) 2
    GINGIVAL PAIN 1/61 (1.6%) 1 0/62 (0%) 0
    GINGIVITIS 1/61 (1.6%) 1 1/62 (1.6%) 1
    HAEMATEMESIS 0/61 (0%) 0 1/62 (1.6%) 1
    LIP PAIN 1/61 (1.6%) 1 0/62 (0%) 0
    MOUTH ULCERATION 1/61 (1.6%) 1 0/62 (0%) 0
    NAUSEA 21/61 (34.4%) 26 26/62 (41.9%) 32
    ORAL PAIN 1/61 (1.6%) 2 0/62 (0%) 0
    REFLUX GASTRITIS 0/61 (0%) 0 1/62 (1.6%) 1
    STOMATITIS 3/61 (4.9%) 3 3/62 (4.8%) 6
    TOOTHACHE 3/61 (4.9%) 3 1/62 (1.6%) 1
    VOMITING 9/61 (14.8%) 11 14/62 (22.6%) 16
    CONSTIPATION 14/61 (23%) 15 10/62 (16.1%) 11
    MELAENA 1/61 (1.6%) 1 0/62 (0%) 0
    PROCTALGIA 1/61 (1.6%) 1 0/62 (0%) 0
    General disorders
    CHILLS 1/61 (1.6%) 1 1/62 (1.6%) 1
    FACE OEDEMA 0/61 (0%) 0 1/62 (1.6%) 1
    FATIGUE 15/61 (24.6%) 15 19/62 (30.6%) 24
    GENERALISED OEDEMA 0/61 (0%) 0 2/62 (3.2%) 2
    INFLUENZA LIKE ILLNESS 2/61 (3.3%) 5 3/62 (4.8%) 3
    IRRITABILITY 0/61 (0%) 0 2/62 (3.2%) 2
    LOCALISED OEDEMA 0/61 (0%) 0 1/62 (1.6%) 1
    MUCOSAL INFLAMMATION 4/61 (6.6%) 4 1/62 (1.6%) 1
    NON-CARDIAC CHEST PAIN 0/61 (0%) 0 2/62 (3.2%) 2
    OEDEMA 1/61 (1.6%) 1 2/62 (3.2%) 2
    OEDEMA PERIPHERAL 3/61 (4.9%) 3 6/62 (9.7%) 7
    PAIN 3/61 (4.9%) 3 2/62 (3.2%) 2
    PYREXIA 6/61 (9.8%) 7 13/62 (21%) 16
    ASTHENIA 19/61 (31.1%) 29 15/62 (24.2%) 22
    Hepatobiliary disorders
    HEPATOTOXICITY 0/61 (0%) 0 1/62 (1.6%) 1
    JAUNDICE 0/61 (0%) 0 2/62 (3.2%) 2
    LIVER DISORDER 0/61 (0%) 0 1/62 (1.6%) 1
    HYPERBILIRUBINAEMIA 1/61 (1.6%) 1 0/62 (0%) 0
    Infections and infestations
    ANAL ABSCESS 0/61 (0%) 0 1/62 (1.6%) 1
    BRONCHIOLITIS 1/61 (1.6%) 1 0/62 (0%) 0
    BRONCHOPNEUMONIA 2/61 (3.3%) 2 0/62 (0%) 0
    HERPES ZOSTER 2/61 (3.3%) 2 1/62 (1.6%) 1
    NASOPHARYNGITIS 3/61 (4.9%) 5 4/62 (6.5%) 7
    PHARYNGITIS 1/61 (1.6%) 1 2/62 (3.2%) 2
    PNEUMONIA 1/61 (1.6%) 1 1/62 (1.6%) 1
    RASH PUSTULAR 0/61 (0%) 0 1/62 (1.6%) 1
    RHINITIS 1/61 (1.6%) 1 1/62 (1.6%) 1
    TONSILLITIS 1/61 (1.6%) 1 0/62 (0%) 0
    UPPER RESPIRATORY TRACT INFECTION 5/61 (8.2%) 9 5/62 (8.1%) 5
    BRONCHITIS 1/61 (1.6%) 1 2/62 (3.2%) 2
    FURUNCLE 1/61 (1.6%) 1 0/62 (0%) 0
    HERPES VIRUS INFECTION 1/61 (1.6%) 1 0/62 (0%) 0
    PARONYCHIA 0/61 (0%) 0 1/62 (1.6%) 1
    SEPSIS 1/61 (1.6%) 1 1/62 (1.6%) 1
    Injury, poisoning and procedural complications
    EXCORIATION 1/61 (1.6%) 1 0/62 (0%) 0
    PROCEDURAL PAIN 1/61 (1.6%) 1 0/62 (0%) 0
    Investigations
    AMYLASE INCREASED 1/61 (1.6%) 1 0/62 (0%) 0
    ASPARTATE AMINOTRANSFERASE INCREASED 5/61 (8.2%) 6 4/62 (6.5%) 5
    BLOOD ALKALINE PHOSPHATASE INCREASED 0/61 (0%) 0 1/62 (1.6%) 1
    BLOOD BILIRUBIN INCREASED 0/61 (0%) 0 1/62 (1.6%) 1
    BLOOD CREATININE INCREASED 1/61 (1.6%) 4 0/62 (0%) 0
    GAMMA-GLUTAMYLTRANSFERASE INCREASED 3/61 (4.9%) 3 5/62 (8.1%) 5
    HAEMOGLOBIN 0/61 (0%) 0 1/62 (1.6%) 3
    HAEMOGLOBIN DECREASED 2/61 (3.3%) 2 2/62 (3.2%) 2
    NEUTROPHIL COUNT DECREASED 2/61 (3.3%) 11 1/62 (1.6%) 1
    WEIGHT DECREASED 4/61 (6.6%) 4 1/62 (1.6%) 1
    WHITE BLOOD CELL COUNT DECREASED 1/61 (1.6%) 1 1/62 (1.6%) 1
    ALANINE AMINOTRANSFERASE INCREASED 4/61 (6.6%) 5 4/62 (6.5%) 6
    Metabolism and nutrition disorders
    DECREASED APPETITE 23/61 (37.7%) 30 25/62 (40.3%) 34
    HYPERGLYCAEMIA 3/61 (4.9%) 4 2/62 (3.2%) 2
    HYPERKALAEMIA 0/61 (0%) 0 1/62 (1.6%) 1
    HYPERMAGNESAEMIA 0/61 (0%) 0 1/62 (1.6%) 1
    HYPOALBUMINAEMIA 1/61 (1.6%) 2 3/62 (4.8%) 3
    HYPOCALCAEMIA 0/61 (0%) 0 1/62 (1.6%) 1
    HYPOKALAEMIA 0/61 (0%) 0 4/62 (6.5%) 4
    HYPOMAGNESAEMIA 0/61 (0%) 0 2/62 (3.2%) 2
    HYPONATRAEMIA 1/61 (1.6%) 1 1/62 (1.6%) 1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 2/61 (3.3%) 2 4/62 (6.5%) 4
    BACK PAIN 3/61 (4.9%) 3 6/62 (9.7%) 7
    BONE PAIN 0/61 (0%) 0 4/62 (6.5%) 8
    FLANK PAIN 0/61 (0%) 0 1/62 (1.6%) 1
    MUSCULOSKELETAL CHEST PAIN 2/61 (3.3%) 4 2/62 (3.2%) 2
    MUSCULOSKELETAL PAIN 1/61 (1.6%) 1 1/62 (1.6%) 4
    MYALGIA 10/61 (16.4%) 17 22/62 (35.5%) 32
    NECK PAIN 1/61 (1.6%) 1 0/62 (0%) 0
    PAIN IN EXTREMITY 3/61 (4.9%) 3 3/62 (4.8%) 4
    POLYMYALGIA RHEUMATICA 0/61 (0%) 0 1/62 (1.6%) 1
    Nervous system disorders
    DIZZINESS 11/61 (18%) 12 7/62 (11.3%) 14
    HYPOAESTHESIA 0/61 (0%) 0 2/62 (3.2%) 2
    LUMBAR RADICULOPATHY 1/61 (1.6%) 1 0/62 (0%) 0
    NEUROPATHY PERIPHERAL 22/61 (36.1%) 22 13/62 (21%) 15
    PARAESTHESIA 1/61 (1.6%) 1 0/62 (0%) 0
    PERIPHERAL SENSORY NEUROPATHY 8/61 (13.1%) 8 10/62 (16.1%) 11
    SYNCOPE 1/61 (1.6%) 1 0/62 (0%) 0
    DYSGEUSIA 1/61 (1.6%) 1 1/62 (1.6%) 1
    HEADACHE 3/61 (4.9%) 3 4/62 (6.5%) 5
    Psychiatric disorders
    ANXIETY 0/61 (0%) 0 2/62 (3.2%) 2
    DISORIENTATION 1/61 (1.6%) 1 0/62 (0%) 0
    MENTAL DISORDER 1/61 (1.6%) 1 0/62 (0%) 0
    MOOD ALTERED 1/61 (1.6%) 1 0/62 (0%) 0
    DEPRESSION 1/61 (1.6%) 1 3/62 (4.8%) 3
    INSOMNIA 7/61 (11.5%) 8 4/62 (6.5%) 6
    Renal and urinary disorders
    DYSURIA 3/61 (4.9%) 3 5/62 (8.1%) 5
    HAEMOGLOBINURIA 1/61 (1.6%) 1 0/62 (0%) 0
    HYDRONEPHROSIS 0/61 (0%) 0 1/62 (1.6%) 1
    MICTURITION URGENCY 1/61 (1.6%) 1 0/62 (0%) 0
    NOCTURIA 1/61 (1.6%) 1 0/62 (0%) 0
    POLLAKIURIA 1/61 (1.6%) 1 0/62 (0%) 0
    URETHRAL PAIN 1/61 (1.6%) 1 0/62 (0%) 0
    URINARY RETENTION 1/61 (1.6%) 1 0/62 (0%) 0
    Reproductive system and breast disorders
    GENITAL RASH 0/61 (0%) 0 1/62 (1.6%) 1
    PELVIC DISCOMFORT 1/61 (1.6%) 1 0/62 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE 0/61 (0%) 0 1/62 (1.6%) 1
    COUGH 10/61 (16.4%) 10 7/62 (11.3%) 8
    DYSPHONIA 0/61 (0%) 0 3/62 (4.8%) 3
    DYSPNOEA 2/61 (3.3%) 2 10/62 (16.1%) 13
    DYSPNOEA EXERTIONAL 0/61 (0%) 0 2/62 (3.2%) 2
    EPISTAXIS 1/61 (1.6%) 1 0/62 (0%) 0
    HAEMOPTYSIS 1/61 (1.6%) 1 0/62 (0%) 0
    HICCUPS 2/61 (3.3%) 2 4/62 (6.5%) 5
    NASAL CONGESTION 1/61 (1.6%) 1 0/62 (0%) 0
    NASAL DISCOMFORT 1/61 (1.6%) 1 0/62 (0%) 0
    ORGANISING PNEUMONIA 0/61 (0%) 0 1/62 (1.6%) 1
    OROPHARYNGEAL PAIN 4/61 (6.6%) 4 3/62 (4.8%) 3
    PRODUCTIVE COUGH 0/61 (0%) 0 7/62 (11.3%) 8
    PULMONARY EMBOLISM 0/61 (0%) 0 1/62 (1.6%) 1
    SPUTUM INCREASED 2/61 (3.3%) 2 2/62 (3.2%) 2
    TONSILLAR INFLAMMATION 0/61 (0%) 0 1/62 (1.6%) 1
    RHINORRHOEA 7/61 (11.5%) 11 0/62 (0%) 0
    Skin and subcutaneous tissue disorders
    ALOPECIA 30/61 (49.2%) 30 29/62 (46.8%) 29
    BLISTER 1/61 (1.6%) 1 0/62 (0%) 0
    DERMATITIS ACNEIFORM 1/61 (1.6%) 1 1/62 (1.6%) 1
    HYPERHIDROSIS 0/61 (0%) 0 1/62 (1.6%) 1
    NAIL DISORDER 1/61 (1.6%) 1 1/62 (1.6%) 1
    ONYCHOLYSIS 0/61 (0%) 0 1/62 (1.6%) 1
    PRURITUS 8/61 (13.1%) 11 3/62 (4.8%) 4
    RASH 8/61 (13.1%) 10 8/62 (12.9%) 11
    SKIN DISORDER 1/61 (1.6%) 1 0/62 (0%) 0
    SKIN HYPERPIGMENTATION 1/61 (1.6%) 1 0/62 (0%) 0
    URTICARIA 1/61 (1.6%) 1 0/62 (0%) 0
    Vascular disorders
    HOT FLUSH 0/61 (0%) 0 1/62 (1.6%) 1
    HYPOTENSION 1/61 (1.6%) 1 1/62 (1.6%) 1
    PERIPHERAL COLDNESS 0/61 (0%) 0 1/62 (1.6%) 1
    PHLEBITIS 1/61 (1.6%) 1 1/62 (1.6%) 1
    THROMBOSIS 0/61 (0%) 0 1/62 (1.6%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Anitra Fielding
    Organization AstraZeneca
    Phone +44 1625 517178
    Email aztrial_results_posting@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT01063517
    Other Study ID Numbers:
    • D0810C00039
    First Posted:
    Feb 5, 2010
    Last Update Posted:
    Jun 29, 2022
    Last Verified:
    Jun 1, 2022