Dose-finding study comparing efficacy and safety of a PARP inhibitor against Doxil in BRCA+ve advanced ovarian cancer - ICEBERG 3

Study identifier:D0810C00012

ClinicalTrials.gov identifier:NCT00628251

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase II, Open-Label, Randomised, Comparative, International Multicentre Study to Assess the Safety and Efficacy of Different Doses of AZD2281 Given Orally Twice Daily versus Intravenous Liposomal Doxorubicin Given Monthly in Patients With Advanced BRCA1- or BRCA2-Associated Ovarian Cancer who have failed previous platinum-based chemotherapy

Medical condition

ovarian neoplasms

Phase

Phase 2

Healthy volunteers

Study drug

AZD2281, Liposomal Doxorubicin

Sex

Female

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 30 Jul 2008

Primary Completion Date: 15 Sept 2009

Study Completion Date: 19 Sept 2018

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2019 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Randwick, Australia, 2031

Location

Research Site

East Melbourne, Australia, 3002

Location

Research Site

Melbourne, Parkville, Australia, VIC 3050

Location

Research Site

Leuven, Belgium, 3000

Location

Research Site

Köln, Germany, 50937

Location

Research Site

München, Germany, 81377

Location

Research Site

Hospitalet deLlobregat, Spain, 08907

Location

Research Site

Barcelona, Spain, 08035

Arms	Assigned Interventions
Experimental: 1 AZD2281 Oral 200 mg BID	Drug: AZD2281 200mg oral twice daily
Active Comparator: 2 Liposomal Doxorubicin	Drug: Liposomal Doxorubicin 50mg/m2 Monthly Intravenous Other Name: Doxil®
Experimental: 3 AZD2281 Oral 400 mg BID	Drug: AZD2281 400mg Oral twice daily Other Name: Olaparib

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient enrolled on 30 July 2008 and last patient on 3 March 2009 at 25 centres in 9 countries

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
97 of 125 screened women with advanced BRCA 1/2 ovarian cancer who had chemotherapy were randomized

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Participant Flow for 2 periods

Period 1: Randomised part

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
STARTED	32^[1]	32^[2]	33^[3]
COMPLETED	32^[4]	32^[5]	32^[6]
NOT COMPLETED	0	0	1
Withdrawal by Subject	0	0	1

[1]	Patients randomised
[2]	Patients randomised
[3]	Patients randomised
[4]	Patients who received olaparib treatment
[5]	Patients who received olaparib treatment
[6]	1 of 33 patients did not receive Liposomal Doxorubicin. Patient voluntarily discontinued

Period 2: Ongoing Initial Study Treatment at DCO

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
STARTED	32^[1]	32^[2]	32^[3]
Discontinued initial study treatment	22	20	25
Crossover to Olaparib	0	0	14^[4]
Ongoing crossover at DCO	0	0	5
Discontinued crossover	0	0	9
COMPLETED	10^[5]	12^[6]	7^[7]
NOT COMPLETED	22	20	25
Adverse Event	1	2	3
Condition under investigation worsened	19	15	13
Withdrawal by Subject	1	2	1
Other reason	0	1	6
Unknown	1	0	2

[1]	Patients who received treatment
[2]	Patients who received treatment
[3]	Patients who received Liposomal doxorubicin 50 mg/m2
[4]	Crossover dosage was 400 mg bd Olaparib
[5]	Ongoing initial study treatment at primary data cut-off
[6]	Ongoing initial study treatment at primary data cut-off
[7]	Patients ongoing initial study treatment (Liposomal doxorubicin)

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Baseline Measures

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin	Total
Number of Participants [units: Participants]	32	32	33	97
Age Continuous [units: Years] Mean ± Standard Deviation	57.2 ± 8.53	53.8 ± 8.77	54.3 ± 9.32	55.5 ± 8.92
Sex: Female, Male [units: Participants]
Female	32	32	33	97
Male	0	0	0	0
BRCA status [units: Participants]
Deleterious BRCA1 mutation	26	28	27	81
Deleterious BRCA2 mutation	6	4	6	16
Race/Ethnicity, Customized ^[1] [units: Participants]
African-Caribbean	0	0	1	1
Ashkenazi Jewish	8	10	11	29
Sephardic Jewish	0	0	2	2
Not applicable	20	21	19	60
Other	4	1	0	5

Outcome Measures

1. Primary Outcome Measure: Progression free survival (PFS) [ Time Frame: Tumour assessment was to be assessed at screening, every 8 weeks during the study and at the withdrawal visit, up to 56 weeks. (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Primary
Measure Name	Progression free survival (PFS)
Measure Description	PFS was defined as the time to progression from the date of randomisation until the date of radiological assessment of progression per RECIST criteria or death (by any cause in the absence of progression)
Time Frame	Tumour assessment was to be assessed at screening, every 8 weeks during the study and at the withdrawal visit, up to 56 weeks. (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Progression free survival (PFS) [units: Participants]	19	20	20

Statistical Analysis 1 for Progression free survival (PFS)

Groups^[1]	All groups
Method^[3]	Regression, Cox
P-Value^[4]	0.6604
Hazard Ratio (HR)^[5]	0.88
95% Confidence Interval	( 0.51 to 1.56 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 200 or 400 mg bd (n=64) versus liposomal doxorubicin (n=33). A hazard ratio < 1 favours olaparib.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Cox proportional hazards model with factors for treatment, BRCA (1 or 2) and platinum sensitivity (sensitive=1 or resistant/refractory=0).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	If the observed p-value for the combined olaparib groups is <0.02 (1-sided) then the result will be regarded as statistically significant.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Progression free survival (PFS)

Groups^[1]	Olaparib 200 mg bd, Liposomal doxorubicin
Method^[3]	Regression, Cox
P-Value^[4]	0.7794
Hazard Ratio (HR)^[5]	0.91
95% Confidence Interval	( 0.48 to 1.74 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 200 (n=32) versus liposomal doxorubicin (n=33). A hazard ratio < 1 favours olaparib.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Cox proportional hazards model with factors for treatment, BRCA (1 or 2) and platinum sensitivity (sensitive=1 or resistant/refractory=0).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	An observed p-value of <0.005 (1-sided) will be regarded as statistically significant for a given pairwise comparison.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Progression free survival (PFS)

Groups^[1]	Olaparib 400 mg bd, Liposomal doxorubicin
Method^[3]	Regression, Cox
P-Value^[4]	0.6604
Hazard Ratio (HR)^[5]	0.86
95% Confidence Interval	( 0.45 to 1.62 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 400 (n=32) versus liposomal doxorubicin (n=33). A hazard ratio < 1 favours olaparib.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Cox proportional hazards model with factors for treatment, BRCA (1 or 2) and platinum sensitivity (sensitive=1 or resistant/refractory=0).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	An observed p-value of <0.005 (1-sided) will be regarded as statistically significant for a given pairwise comparison.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Progression free survival (PFS) [ Time Frame: Tumour assessment was to be assessed at screening, every 8 weeks during the study and at the withdrawal visit, up to 56 weeks. (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Primary
Measure Name	Progression free survival (PFS)
Measure Description	PFS was defined as the time to progression from the date of randomisation until the date of radiological assessment of progression per RECIST criteria or death (by any cause in the absence of progression)
Time Frame	Tumour assessment was to be assessed at screening, every 8 weeks during the study and at the withdrawal visit, up to 56 weeks. (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Progression free survival (PFS) [units: Months] Median (95% Confidence Interval)	6.5 (5.5 to 10.1)	8.8 (5.4 to 9.2)	7.1 (3.7 to 10.7)

No statistical analysis provided for Progression free survival (PFS)

3. Secondary Outcome Measure: Objective response rate (ORR) [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Objective response rate (ORR)
Measure Description	ORR was defined according to RECIST. Complete response (CR) or partial response - (PR)- 30% decrease Patients with a best RECIST response of CR or PR had to have a confirmed response at least 28 days later.
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Objective response rate (ORR) [units: Participants]
Complete response	0	0	0
Number of Partial responders	8	10	6

Statistical Analysis 1 for Objective response rate (ORR)

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.1291
Odds Ratio (OR)^[5]	2.27
95% Confidence Interval	( 0.79 to 7.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 200 or 400 (n=64) versus liposomal doxorubicin (n=33).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis was performed using logistic regression with factors for treatment, BRCA status and platinum sensitivity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	2-sided p-value
[5]	Other relevant estimation information:
	An odds ratio >1 favoured olaparib

Statistical Analysis 2 for Objective response rate (ORR)

Groups^[1]	Olaparib 200 mg bd, Liposomal doxorubicin
Method^[3]	Regression, Logistic
P-Value^[4]	0.3131
Odds Ratio (OR)^[5]	1.90
95% Confidence Interval	( 0.55 to 7.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 200 (n=32) versus liposomal doxorubicin (n=33).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis was performed using logistic regression with factors for treatment, BRCA status and platinum sensitivity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	2-sided p-value
[5]	Other relevant estimation information:
	An odds ratio >1 favoured olaparib.

Statistical Analysis 3 for Objective response rate (ORR)

Groups^[1]	Olaparib 400 mg bd, Liposomal doxorubicin
Method^[3]	Regression, Logistic
P-Value^[4]	0.1079
Odds Ratio (OR)^[5]	2.69
95% Confidence Interval	( 0.81 to 9.76 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 400 (n=32) versus liposomal doxorubicin (n=33).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The analysis was performed using logistic regression with factors for treatment, BRCA status and platinum sensitivity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	An odds ratio >1 favoured olaparib

4. Secondary Outcome Measure: Disease control rate [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Disease control rate
Measure Description	The number of patients with confirmed CR (disappearance of all target lesions) or PR (30% decrease in the sum of the longest diameter of target lesions ) or SD ( small changes ) >4 months, divided by the number of randomised patients
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Disease control rate [units: Participants]	21	21	19

No statistical analysis provided for Disease control rate

5. Secondary Outcome Measure: Overall duration of response [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Overall duration of response
Measure Description	The duration of response was defined as time (months) from initial assessment of PR/CR until earliest date of objective progression or death. (Values may be underestimated as some patients had not progressed at final analysis so true duration is likely to be greater than that in database.)
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Duration of response is analysed for patients experiencing a response.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Olaparib 200 mg bd + Olaparib 400 mg bd,	Olaparib (AZD2281) 200 or 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Olaparib 200 mg bd + Olaparib 400 mg bd,	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	8	10	18	6
Overall duration of response [units: Months] Median (95% Confidence Interval)	5.95 (3.71 to NA) ^[1]	6.80 (5.52 to 7.39)	6.24 (5.52 to 7.39)	5.49 (4.67 to 9.13)

No statistical analysis provided for Overall duration of response

6. Secondary Outcome Measure: Best percentage change in tumour size [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Best percentage change in tumour size
Measure Description	The percentage change (reduction) from baseline in the sum of the lengths of the longest diameter (LD) of the RECIST target lesions were objectively documented, regardless of whether the patient was still taking study medication
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Best percentage change in tumour size [units: Percent change] Median (Full Range)	-15.90 (-75.30 to 31.48)	-24.60 (-100.00 to 51.10)	-14.3 (-87.5 to 32.4)

No statistical analysis provided for Best percentage change in tumour size

7. Secondary Outcome Measure: Best percentage change from baseline in CA-125 levels [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Best percentage change from baseline in CA-125 levels
Measure Description	Best percentage change in cancer antigen 125 (CA-125) levels
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	30	31	33
Best percentage change from baseline in CA-125 levels [units: Percent change] Median (Full Range)	-37.42 (-98.77 to 327.76)	-71.19 (-96.88 to 70.56)	-55.8 (-99.5 to 192.1)

No statistical analysis provided for Best percentage change from baseline in CA-125 levels

8. Secondary Outcome Measure: Confirmed RECIST response and/or CA-125 response [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Confirmed RECIST response and/or CA-125 response
Measure Description	The percentage of patients reporting a RECIST confirmed response and/or a CA-125 response (in the absence of progression). A CA-125 response was defined as a confirmed greater or equal to 50% reduction in CA-125.
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Confirmed RECIST response and/or CA-125 response [units: Percentage of participants]	37.5	59.4	39.4

No statistical analysis provided for Confirmed RECIST response and/or CA-125 response

9. Secondary Outcome Measure: Overall survival (OS) [ Time Frame: At the time of the cut-off for the final analysis of overall survival (30 April 2010) ]

Measure Type	Secondary
Measure Name	Overall survival (OS)
Measure Description	OS was defined as time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date they were known to be alive. Median OS was not calculable for olaparib groups due to an insufficient number of deaths so the percentage of participants who died are shown along with 95% confidence intervals
Time Frame	At the time of the cut-off for the final analysis of overall survival (30 April 2010)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Overall survival (OS) [units: Participants]	9	11	13

Statistical Analysis 1 for Overall survival (OS)

Groups^[1]	All groups
Method^[3]	Regression, Cox
P-Value^[4]	0.5781
Hazard Ratio (HR)^[5]	0.82
95% Confidence Interval	( 0.41 to 1.70 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 200 or 400 (n=64) versus liposomal doxorubicin (n=33).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis was performed using a Cox proportional hazards model with factors for treatment, BRCA status and platinum sensitivity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	2-sided p-value
[5]	Other relevant estimation information:
	A hazard ratio of <1 favoured olaparib.

Statistical Analysis 2 for Overall survival (OS)

Groups^[1]	Olaparib 200 mg bd, Liposomal doxorubicin
Method^[3]	Regression, Cox
P-Value^[4]	0.3417
Hazard Ratio (HR)^[5]	0.66
95% Confidence Interval	( 0.27 to 1.55 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 200 (n=32) versus liposomal doxorubicin (n=33).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis was performed using a Cox proportional hazards model with factors for treatment, BRCA status and platinum sensitivity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	2-sided p-value
[5]	Other relevant estimation information:
	A hazard ratio of <1 favoured olaparib.

Statistical Analysis 3 for Overall survival (OS)

Groups^[1]	Olaparib 400 mg bd, Liposomal doxorubicin
Method^[3]	Regression, Cox
P-Value^[4]	0.9877
Hazard Ratio (HR)^[5]	1.01
95% Confidence Interval	( 0.44 to 2.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of olaparib 400 (n=32) versus liposomal doxorubicin (n=33).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis was performed using a Cox proportional hazards model with factors for treatment, BRCA status and platinum sensitivity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	2-sided p-value
[5]	Other relevant estimation information:
	A hazard ratio of <1 favoured olaparib.

10. Secondary Outcome Measure: Best quality of life (QoL) response for Trial Outcome Index (TOI) [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Best quality of life (QoL) response for Trial Outcome Index (TOI)
Measure Description	Best HRQoL response using the TOI endpoint. Improvement was defined as a change from baseline of greater than or equal to +7. The TOI score ranges from 0-100.
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Evaluable for TOI at baseline

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Best quality of life (QoL) response for Trial Outcome Index (TOI) [units: Participants]
Improved	7	5	3
No change	10	10	11
Worsened	3	7	6
Non-evaluable	5	7	7

No statistical analysis provided for Best quality of life (QoL) response for Trial Outcome Index (TOI)

11. Secondary Outcome Measure: Best QoL response for total Functional Analysis of Cancer Therapy - Ovarian (FACT-O) [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Best QoL response for total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)
Measure Description	Best HRQoL response using the total FACT-O endpoint. Improvement was defined as a change from baseline of greater than or equal to +9.
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Evaluable for FACT-O at baseline

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Best QoL response for total Functional Analysis of Cancer Therapy - Ovarian (FACT-O) [units: Participants]
Improved	3	6	1
No Change	14	11	11
Worsened	3	5	7
Non-evaluable	5	7	8

No statistical analysis provided for Best QoL response for total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)

12. Secondary Outcome Measure: Best QoL response for FACT-O symptom index (FOSI) [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

Measure Type	Secondary
Measure Name	Best QoL response for FACT-O symptom index (FOSI)
Measure Description	Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.
Time Frame	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Evaluable for FOSI at baseline

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Measured Values

	Olaparib 200 mg bd	Olaparib 400 mg bd	Liposomal doxorubicin
Number of Participants Analyzed [units:participants]	32	32	33
Best QoL response for FACT-O symptom index (FOSI) [units: Participants]
Improved	5	4	3
No change	14	9	10
Worsened	1	9	7
Non-evaluable	5	7	7

No statistical analysis provided for Best QoL response for FACT-O symptom index (FOSI)

Serious Adverse Events

Time Frame	No text entered.
Additional Description	AEs reported = all events up to OS data cut-off. After PFS data cut-off, AEs only collected for olaparib and cross-over groups. The safety profile of these 2 groups at OS was consistent with that at time of PFS. One patient was recorded as crossing over to olaparib but not receiving cross-over treatment.

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Serious Adverse Events

Olaparib 200 mg bd

Olaparib 400 mg bd

Liposomal doxorubicin

Total, serious adverse events

# participants affected / at risk

5/32 (15.63%)

6/32 (18.75%)

5/32 (15.63%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

Gastrointestinal disorders

Abdominal Pain Lower¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

Gastrointestinal disorders

Intestinal Obstruction¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

Gastrointestinal disorders

Small Intestinal Obstruction¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

0/32 (0.00%)

Gastrointestinal disorders

Subileus¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

0/32 (0.00%)

General disorders

Fatigue¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

1/32 (3.13%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

0/32 (0.00%)

Hepatobiliary disorders

Cholelithiasis¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

Infections and infestations

Bacteraemia¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

0/32 (0.00%)

Injury, poisoning and procedural complications

Overdose¹,^†

# participants affected / at risk

0/32 (0.00%)

Injury, poisoning and procedural complications

Haemoglobin Decreased¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

0/32 (0.00%)

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

0/32 (0.00%)

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

0/32 (0.00%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

0/32 (0.00%)

Musculoskeletal and connective tissue disorders

Intervertebral Disc Degeneration¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

0/32 (0.00%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Chest Pain¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myelodysplastic Syndrome¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

Nervous system disorders

Cerebrovascular Accident¹,^†

# participants affected / at risk

2/32 (6.25%)

0/32 (0.00%)

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

1/32 (3.13%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

Vascular disorders

Deep Vein Thrombosis¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	AEs reported = all events up to OS data cut-off. After PFS data cut-off, AEs only collected for olaparib and cross-over groups. The safety profile of these 2 groups at OS was consistent with that at time of PFS. One patient was recorded as crossing over to olaparib but not receiving cross-over treatment.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Olaparib 200 mg bd	Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd	Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal doxorubicin	Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Other Adverse Events

Olaparib 200 mg bd

Olaparib 400 mg bd

Liposomal doxorubicin

Total, other (not including serious) adverse events

# participants affected / at risk

32/32 (100.00%)

31/32 (96.88%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

4/32 (12.50%)

11/32 (34.38%)

2/32 (6.25%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

2/32 (6.25%)

3/32 (9.38%)

6/32 (18.75%)

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

5/32 (15.63%)

2/32 (6.25%)

1/32 (3.13%)

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

2/32 (6.25%)

0/32 (0.00%)

1/32 (3.13%)

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

1/32 (3.13%)

Eye disorders

Dry Eye¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

19/32 (59.38%)

25/32 (78.13%)

18/32 (56.25%)

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

19/32 (59.38%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

11/32 (34.38%)

16/32 (50.00%)

10/32 (31.25%)

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

12/32 (37.50%)

8/32 (25.00%)

12/32 (37.50%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

9/32 (28.13%)

6/32 (18.75%)

12/32 (37.50%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

8/32 (25.00%)

12/32 (37.50%)

10/32 (31.25%)

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

5/32 (15.63%)

7/32 (21.88%)

Gastrointestinal disorders

Abdominal Distension¹,^†

# participants affected / at risk

3/32 (9.38%)

5/32 (15.63%)

Gastrointestinal disorders

Dry Mouth¹,^†

# participants affected / at risk

0/32 (0.00%)

4/32 (12.50%)

3/32 (9.38%)

Gastrointestinal disorders

Flatulence¹,^†

# participants affected / at risk

2/32 (6.25%)

4/32 (12.50%)

2/32 (6.25%)

Gastrointestinal disorders

Gastrooesophageal Reflux Disease¹,^†

# participants affected / at risk

1/32 (3.13%)

3/32 (9.38%)

2/32 (6.25%)

Gastrointestinal disorders

Haemorrhoids¹,^†

# participants affected / at risk

1/32 (3.13%)

3/32 (9.38%)

Gastrointestinal disorders

Abdominal Discomfort¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

0/32 (0.00%)

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

1/32 (3.13%)

2/32 (6.25%)

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

2/32 (6.25%)

0/32 (0.00%)

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

2/32 (6.25%)

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

0/32 (0.00%)

Gastrointestinal disorders

Intestinal Obstruction¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

Gastrointestinal disorders

Mouth Ulceration¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

Gastrointestinal disorders

Oral Pain¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

2/32 (6.25%)

Gastrointestinal disorders

Salivary Hypersecretion¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

0/32 (0.00%)

General disorders

Fatigue¹,^†

# participants affected / at risk

12/32 (37.50%)

21/32 (65.63%)

14/32 (43.75%)

General disorders

Asthenia¹,^†

# participants affected / at risk

6/32 (18.75%)

11/32 (34.38%)

4/32 (12.50%)

General disorders

Mucosal Inflammation¹,^†

# participants affected / at risk

0/32 (0.00%)

7/32 (21.88%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

1/32 (3.13%)

4/32 (12.50%)

General disorders

Chills¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

3/32 (9.38%)

General disorders

Oedema Peripheral¹,^†

# participants affected / at risk

2/32 (6.25%)

3/32 (9.38%)

2/32 (6.25%)

General disorders

Pain¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

2/32 (6.25%)

Immune system disorders

Drug Hypersensitivity¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

5/32 (15.63%)

11/32 (34.38%)

4/32 (12.50%)

Infections and infestations

Upper Respiratory Tract Infection¹,^†

# participants affected / at risk

5/32 (15.63%)

2/32 (6.25%)

Infections and infestations

Influenza¹,^†

# participants affected / at risk

3/32 (9.38%)

2/32 (6.25%)

1/32 (3.13%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

2/32 (6.25%)

3/32 (9.38%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/32 (3.13%)

2/32 (6.25%)

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

Infections and infestations

Intertrigo Candida¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

Infections and infestations

Rhinitis¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

0/32 (0.00%)

Infections and infestations

Tinea Pedis¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

Infections and infestations

Tonsillitis¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

0/32 (0.00%)

Infections and infestations

Viral Infection¹,^†

# participants affected / at risk

2/32 (6.25%)

1/32 (3.13%)

Infections and infestations

Body Temperature Increased¹,^†

# participants affected / at risk

1/32 (3.13%)

3/32 (9.38%)

0/32 (0.00%)

Infections and infestations

Weight Decreased¹,^†

# participants affected / at risk

2/32 (6.25%)

Metabolism and nutrition disorders

Decreased Appetite¹,^†

# participants affected / at risk

5/32 (15.63%)

8/32 (25.00%)

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

2/32 (6.25%)

1/32 (3.13%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

3/32 (9.38%)

6/32 (18.75%)

5/32 (15.63%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

3/32 (9.38%)

0/32 (0.00%)

2/32 (6.25%)

Musculoskeletal and connective tissue disorders

Pain In Extremity¹,^†

# participants affected / at risk

1/32 (3.13%)

3/32 (9.38%)

Musculoskeletal and connective tissue disorders

Flank Pain¹,^†

# participants affected / at risk

2/32 (6.25%)

0/32 (0.00%)

Musculoskeletal and connective tissue disorders

Groin Pain¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

2/32 (6.25%)

Musculoskeletal and connective tissue disorders

Muscle Spasms¹,^†

# participants affected / at risk

2/32 (6.25%)

0/32 (0.00%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Chest Pain¹,^†

# participants affected / at risk

0/32 (0.00%)

1/32 (3.13%)

2/32 (6.25%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Pain¹,^†

# participants affected / at risk

2/32 (6.25%)

1/32 (3.13%)

2/32 (6.25%)

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

2/32 (6.25%)

1/32 (3.13%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

8/32 (25.00%)

9/32 (28.13%)

8/32 (25.00%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

2/32 (6.25%)

7/32 (21.88%)

3/32 (9.38%)

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

5/32 (15.63%)

0/32 (0.00%)

Nervous system disorders

Neuropathy Peripheral¹,^†

# participants affected / at risk

2/32 (6.25%)

3/32 (9.38%)

2/32 (6.25%)

Nervous system disorders

Memory Impairment¹,^†

# participants affected / at risk

2/32 (6.25%)

1/32 (3.13%)

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

3/32 (9.38%)

4/32 (12.50%)

2/32 (6.25%)

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

2/32 (6.25%)

1/32 (3.13%)

2/32 (6.25%)

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

1/32 (3.13%)

2/32 (6.25%)

0/32 (0.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

6/32 (18.75%)

5/32 (15.63%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

2/32 (6.25%)

4/32 (12.50%)

Respiratory, thoracic and mediastinal disorders

Oropharyngeal Pain¹,^†

# participants affected / at risk

4/32 (12.50%)

1/32 (3.13%)

2/32 (6.25%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea Exertional¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

0/32 (0.00%)

Respiratory, thoracic and mediastinal disorders

Productive Cough¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

0/32 (0.00%)

Skin and subcutaneous tissue disorders

Palmar-Plantar Erythrodysaesthesia Syndrome¹,^†

# participants affected / at risk

0/32 (0.00%)

20/32 (62.50%)

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

3/32 (9.38%)

14/32 (43.75%)

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

3/32 (9.38%)

4/32 (12.50%)

7/32 (21.88%)

Skin and subcutaneous tissue disorders

Erythema¹,^†

# participants affected / at risk

0/32 (0.00%)

6/32 (18.75%)

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

0/32 (0.00%)

5/32 (15.63%)

Skin and subcutaneous tissue disorders

Blister¹,^†

# participants affected / at risk

0/32 (0.00%)

4/32 (12.50%)

Skin and subcutaneous tissue disorders

Dry Skin¹,^†

# participants affected / at risk

1/32 (3.13%)

0/32 (0.00%)

4/32 (12.50%)

Skin and subcutaneous tissue disorders

Skin Hyperpigmentation¹,^†

# participants affected / at risk

0/32 (0.00%)

3/32 (9.38%)

Skin and subcutaneous tissue disorders

Exfoliative Rash¹,^†

# participants affected / at risk

0/32 (0.00%)

2/32 (6.25%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

0/32 (0.00%)

7/32 (21.88%)

1/32 (3.13%)

Vascular disorders

Hot Flush¹,^†

# participants affected / at risk

4/32 (12.50%)

1/32 (3.13%)

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

2/32 (6.25%)

0/32 (0.00%)

1/32 (3.13%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary,

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	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.
	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 more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No publication of the study results may be made until publication of the results of the multi-centre study or 2 years after study completion, whichever is the sooner

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The AEs reported include all events up to the OS data cut-off. After the PFS data cut-off, AEs were only collected for the olaparib and cross-over groups. The safety profile of these 2 groups at OS was consistent with that at the time of PFS.

Results Point of Contact

Name/Title:	Paula del Rosario
Organization:	AstraZeneca
Phone	+44 7884 735492
E-mail:	[email protected]

Documents available

Cancer Study Locator (US and Canada only)
Download
CSR_Synopsis_D0810C00012.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

AstraZeneca Cancer Study Locator Service

877-400-4656

astrazeneca@emergingmed.com

Investigators

Principal Investigator

Jane Robertson

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Cancer Study Locator (US and Canada only)

CSR_Synopsis_D0810C00012.pdf

Trial Results Summaries