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Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments (SOLO3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02282020
Recruitment Status : Active, not recruiting
First Posted : November 4, 2014
Results First Posted : December 2, 2019
Last Update Posted : October 28, 2020
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
Interventions Drug: OLAPARIB
Drug: Single agent chemotherapy
Enrollment 266
Recruitment Details A wash-out period of up to 5 weeks was required for participants who have previously taken potent inhibitors or CYP3A4/5 inducers.
Pre-assignment Details Participants were randomized in a 2:1 ratio between olaparib and selected chemotherapy.
Arm/Group Title Olaparib 300mg BID Selected Chemotherapy
Hide Arm/Group Description Participants received olaparib twice daily as a 300 mg tablet. Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Period Title: Overall Study
Started 178 88
Received Treatment 178 76
Completed 43 1
Not Completed 135 87
Reason Not Completed
Objective Disease Progression             111             30
Adverse Event             13             15
Withdrawal by Subject             5             10
Miscellaneous             4             17
Severe Non-compliance to Protocol             1             0
Developed Discontinuation Criteria             1             3
Withdrew Consent Prior to Dosing             0             12
Arm/Group Title Olaparib 300mg BID Selected Chemotherapy Total
Hide Arm/Group Description Participants received olaparib twice daily as a 300 mg tablet. Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine. Total of all reporting groups
Overall Number of Baseline Participants 178 88 266
Hide Baseline Analysis Population Description
Baseline characteristics are displayed for all participants who started the study. This includes the 12 participants who did not receive treatment in the 'Selected Chemotherapy' arm.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 178 participants 88 participants 266 participants
58.5  (9.27) 60.4  (9.9) 59.2  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 178 participants 88 participants 266 participants
Female
178
 100.0%
88
 100.0%
266
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 178 participants 88 participants 266 participants
Hispanic or Latino
31
  17.4%
16
  18.2%
47
  17.7%
Not Hispanic or Latino
146
  82.0%
72
  81.8%
218
  82.0%
Unknown or Not Reported
1
   0.6%
0
   0.0%
1
   0.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 178 participants 88 participants 266 participants
White 148 75 223
Black Or African American 1 1 2
Asian 24 10 34
American Indian Or Alaska Native 4 2 6
Other 1 0 1
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description

Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used by a Blinded Independent Central Review (BICR) to assess participant response to treatment

Objective Response Rate (ORR) is the number of participants with Complete Response (CR) or Partial Response (PR) in the Measurable Disease Analysis Set (MDAS). Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each. Partial response is declared when there is a decrease in sum of diameters of target lesions ≥ 30%.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 151 72
Measure Type: Number
Unit of Measure: Count of Participants
109 37
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.53
Confidence Interval (2-Sided) 95%
1.40 to 4.58
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description RECIST 1.1 criteria was used to assess participant response to treatment. PFS was defined as the time from randomization until the date of objective radiological disease progression according to RECIST 1.1 or death (by any cause in the absence of disease progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to disease progression (i.e., date of RECIST progression/death or censoring - date of randomization +1).
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 178 88
Median (95% Confidence Interval)
Unit of Measure: Months
13.4
(10.9 to 14.1)
9.2
(7.6 to 11.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.43 to 0.91
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time From Randomisation to Second Progression (PFS2)
Hide Description Time from randomization to PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to first progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could involve objective radiological, clinical, cancer antigen-125 (CA-125) progression or death. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG) criteria.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 178 88
Median (95% Confidence Interval)
Unit of Measure: Months
23.6
(19.2 to 28.4)
19.6
(17.0 to 22.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.354
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.52 to 1.26
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description [Not Specified]
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 178 88
Median (95% Confidence Interval)
Unit of Measure: Months
37.8 [1] 
(29.9 to NA)
39.4 [1] 
(24.2 to NA)
[1]
Upper limit not reached
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.780
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.65 to 1.76
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death
Hide Description Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG).
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 178 88
Median (95% Confidence Interval)
Unit of Measure: Months
11.1
(9.7 to 13.8)
7.9
(6.9 to 9.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.41 to 0.85
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time From Randomization To First Subsequent Therapy Or Death (TFST)
Hide Description TFST was defined as the time from the date of randomization to the earlier of first subsequent therapy start date or death.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 178 88
Median (95% Confidence Interval)
Unit of Measure: Months
15.1
(13.2 to 17.6)
10.2
(8.3 to 13.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.33 to 0.71
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Time From Randomization To Second Subsequent Therapy Or Death (TSST)
Hide Description TSST was defined as the time from the date of randomization to the earlier of second subsequent chemotherapy start date following study treatment discontinuation, or death.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 178 88
Median (95% Confidence Interval)
Unit of Measure: Months
25.2
(19.4 to 26.3)
17.1
(15.5 to 20.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.31 to 0.77
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Time From Randomization To Study Treatment Discontinuation Or Death (TDT)
Hide Description TDT was defined as the time from randomization to the earlier of the date of study treatment discontinuation or death.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 178 88
Median (95% Confidence Interval)
Unit of Measure: Months
13.3
(10.2 to 15.0)
5.1
(4.7 to 6.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.11 to 0.25
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Duration of Response (DoR)
Hide Description Duration of response is the time from the first documentation of complete response (CR) or partial response (PR) until the date of progression or death, or the last evaluable RECIST assessment for participants that do not progress or progress after 2 missed assessments. Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 109 37
Median (Inter-Quartile Range)
Unit of Measure: Months
9.4
(5.6 to 25.7)
10.2
(5.5 to 15.3)
10.Secondary Outcome
Title Time to Response (TTR)
Hide Description TTR was defined as the time from randomization until the date of first documented response by Blinded independent central review (BICR) assessment.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 109 37
Median (Inter-Quartile Range)
Unit of Measure: Months
2.0
(1.8 to 3.9)
3.5
(1.8 to 3.7)
11.Secondary Outcome
Title Mean Change From Baseline In Trial Outcome Index (TOI) Score
Hide Description The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. A negative change in score from baseline indicated a worsening in symptoms.
Time Frame Baseline (Day 1) to Week 48 (±1 week)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 167 62
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-2.4  (11.1) -3.6  (9.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.108
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
-0.5 to 5.5
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Number of Participants Who Show an Improvement in TOI Score
Hide Description The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher health-related quality of life (HRQoL). A change in at least 10 points was considered clinically relevant.
Time Frame Baseline (Day 1) to Week 48 (±1 week)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 168 69
Measure Type: Number
Unit of Measure: Count of Participants
25 5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.092
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.24
Confidence Interval (2-Sided) 95%
0.88 to 6.86
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)
Hide Description

BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).

The number of participants with complete or partial response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Partial response is declared when there is a decrease in sum of target disease ≥ 30%. Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 144 70
Measure Type: Number
Unit of Measure: Count of Participants
103 36
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.40
Confidence Interval (2-Sided) 95%
1.32 to 4.39
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)
Hide Description

BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).

Progressive disease was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 170 88
Measure Type: Number
Unit of Measure: Count of Participants
105 48
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.42 to 0.91
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population
Hide Description BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 170 84
Measure Type: Number
Unit of Measure: Count of Participants
77 31
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.393
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.53 to 1.28
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Overall Survival (OS) in BRCA Gene Population
Hide Description

BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).

OS in BRCA gene population was measured by the number of participants who died due to any cause.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 170 84
Measure Type: Number
Unit of Measure: Count of Participants
55 20
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.690
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.67 to 1.83
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population
Hide Description BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 170 84
Measure Type: Number
Unit of Measure: Count of Participants
128 73
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.10 to 0.22
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population
Hide Description BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 170 84
Measure Type: Number
Unit of Measure: Count of Participants
106 51
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.30 to 0.66
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population
Hide Description BRCA gene population includes participants identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (eg, gene sequencing and large rearrangement analysis).
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received. Participants who were randomized but did not subsequently go on to receive study treatment were included in the FAS.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 170 84
Measure Type: Number
Unit of Measure: Count of Participants
81 38
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg BID, Selected Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.30 to 0.76
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Geometric Mean Plasma Concentration of Olaparib
Hide Description [Not Specified]
Time Frame Day 1, 1 hour post-dose and Day 29 pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) analysis set includes all participants who received an olaparib dose and provided evaluable plasma concentration data.
Arm/Group Title Olaparib 300 mg BID
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Overall Number of Participants Analyzed 66
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
Day 1, 1 hour post-dose Number Analyzed 66 participants
4.76
(112.93%)
Day 29, pre-dose Number Analyzed 42 participants
1.78
(100.54%)
21.Secondary Outcome
Title Number of Participants Who Experience at Least One Adverse Event (AE)
Hide Description An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Time Frame Maximum of 45 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set includes all participants who received at least 1 dose of randomized study treatment, olaparib or chemotherapy.
Arm/Group Title Olaparib 300 mg BID Selected Chemotherapy
Hide Arm/Group Description:
Participants received olaparib twice daily as a 300 mg tablet.
Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
Overall Number of Participants Analyzed 178 76
Measure Type: Number
Unit of Measure: Count of Participants
174 73
Time Frame Maximum of 45 Months
Adverse Event Reporting Description

All-Cause Mortality was collected for the Full Analysis Set (FAS), which includes all randomized participants and compares the treatment groups on the basis of randomized treatment, regardless of the treatment actually received.

Serious and Other Adverse Events were collected for the Safety Analysis Set, which includes all participants who received at least 1 dose of randomized study treatment, olaparib or chemotherapy.
 
Arm/Group Title Olaparib 300mg BID Selected Chemotherapy
Hide Arm/Group Description Participants received olaparib twice daily as a 300 mg tablet. Participants received physician's choice of chemotherapy, out of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.
All-Cause Mortality
Olaparib 300mg BID Selected Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   56/178 (31.46%)      21/88 (23.86%)    
Hide Serious Adverse Events
Olaparib 300mg BID Selected Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   42/178 (23.60%)      14/76 (18.42%)    
Blood and lymphatic system disorders     
Anaemia † 1  5/178 (2.81%)  6 0/76 (0.00%)  0
Pancytopenia † 1  2/178 (1.12%)  2 0/76 (0.00%)  0
Cardiac disorders     
Cardiopulmonary failure † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Ear and labyrinth disorders     
Tinnitus † 1  1/178 (0.56%)  2 0/76 (0.00%)  0
Vertigo † 1  1/178 (0.56%)  2 0/76 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Abdominal pain upper † 1  0/178 (0.00%)  0 1/76 (1.32%)  1
Anal inflammation † 1  0/178 (0.00%)  0 1/76 (1.32%)  1
Ascites † 1  1/178 (0.56%)  6 0/76 (0.00%)  0
Ileus † 1  2/178 (1.12%)  2 0/76 (0.00%)  0
Intestinal obstruction † 1  2/178 (1.12%)  3 1/76 (1.32%)  1
Mesenteric vein thrombosis † 1  0/178 (0.00%)  0 1/76 (1.32%)  1
Nausea † 1  2/178 (1.12%)  2 2/76 (2.63%)  2
Oesophagitis † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Small intestinal obstruction † 1  2/178 (1.12%)  2 0/76 (0.00%)  0
Vomiting † 1  3/178 (1.69%)  3 3/76 (3.95%)  3
General disorders     
Asthenia † 1  2/178 (1.12%)  2 1/76 (1.32%)  2
Chest pain † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Malaise † 1  0/178 (0.00%)  0 1/76 (1.32%)  1
Oedema peripheral † 1  0/178 (0.00%)  0 1/76 (1.32%)  1
Pyrexia † 1  2/178 (1.12%)  2 2/76 (2.63%)  2
Hepatobiliary disorders     
Cholecystitis † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Immune system disorders     
Anaphylactic reaction † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Infections and infestations     
Corneal abscess † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Device related infection † 1  0/178 (0.00%)  0 1/76 (1.32%)  1
Gastroenteritis † 1  2/178 (1.12%)  2 0/76 (0.00%)  0
Herpes zoster † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Pneumonia † 1  2/178 (1.12%)  2 1/76 (1.32%)  1
Sepsis † 1  2/178 (1.12%)  2 0/76 (0.00%)  0
Injury, poisoning and procedural complications     
Procedural pain † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Radius fracture † 1  1/178 (0.56%)  1 1/76 (1.32%)  1
Spinal compression fracture † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Subarachnoid haemorrhage † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Investigations     
Blood creatinine increased † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Metabolism and nutrition disorders     
Electrolyte imbalance † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Pain in extremity † 1  0/178 (0.00%)  0 1/76 (1.32%)  1
Rotator cuff syndrome † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia † 1  1/178 (0.56%)  1 1/76 (1.32%)  1
Breast cancer † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Gastric cancer † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Lung neoplasm malignant † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Metastases to lymph nodes † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Myelodysplastic syndrome † 1  2/178 (1.12%)  3 0/76 (0.00%)  0
Nervous system disorders     
Ischaemic stroke † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Syncope † 1  2/178 (1.12%)  2 0/76 (0.00%)  0
Renal and urinary disorders     
Renal failure † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pleural effusion † 1  3/178 (1.69%)  3 2/76 (2.63%)  3
Pulmonary embolism † 1  2/178 (1.12%)  2 0/76 (0.00%)  0
Vascular disorders     
Deep vein thrombosis † 1  3/178 (1.69%)  3 0/76 (0.00%)  0
Embolism † 1  1/178 (0.56%)  1 0/76 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Olaparib 300mg BID Selected Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   172/178 (96.63%)      73/76 (96.05%)    
Blood and lymphatic system disorders     
Anaemia † 1  84/178 (47.19%)  19/76 (25.00%) 
Leukopenia † 1  12/178 (6.74%)  6/76 (7.89%) 
Neutropenia † 1  26/178 (14.61%)  22/76 (28.95%) 
Thrombocytopenia † 1  13/178 (7.30%)  5/76 (6.58%) 
Gastrointestinal disorders     
Abdominal distension † 1  11/178 (6.18%)  1/76 (1.32%) 
Abdominal pain † 1  38/178 (21.35%)  11/76 (14.47%) 
Abdominal pain upper † 1  20/178 (11.24%)  4/76 (5.26%) 
Constipation † 1  22/178 (12.36%)  17/76 (22.37%) 
Diarrhoea † 1  50/178 (28.09%)  13/76 (17.11%) 
Dyspepsia † 1  18/178 (10.11%)  7/76 (9.21%) 
Flatulence † 1  1/178 (0.56%)  4/76 (5.26%) 
Gastrooesophageal reflux disease † 1  10/178 (5.62%)  2/76 (2.63%) 
Nausea † 1  115/178 (64.61%)  24/76 (31.58%) 
Stomatitis † 1  7/178 (3.93%)  14/76 (18.42%) 
Vomiting † 1  68/178 (38.20%)  14/76 (18.42%) 
General disorders     
Asthenia † 1  35/178 (19.66%)  12/76 (15.79%) 
Fatigue † 1  65/178 (36.52%)  20/76 (26.32%) 
Influenza like illness † 1  6/178 (3.37%)  4/76 (5.26%) 
Mucosal inflammation † 1  5/178 (2.81%)  10/76 (13.16%) 
Oedema peripheral † 1  16/178 (8.99%)  10/76 (13.16%) 
Pyrexia † 1  19/178 (10.67%)  8/76 (10.53%) 
Infections and infestations     
Bronchitis † 1  10/178 (5.62%)  2/76 (2.63%) 
Upper respiratory tract infection † 1  15/178 (8.43%)  8/76 (10.53%) 
Urinary tract infection † 1  19/178 (10.67%)  4/76 (5.26%) 
Investigations     
Alanine aminotransferase increased † 1  5/178 (2.81%)  4/76 (5.26%) 
Blood creatinine increased † 1  13/178 (7.30%)  1/76 (1.32%) 
Neutrophil count decreased † 1  16/178 (8.99%)  10/76 (13.16%) 
White blood cell count decreased † 1  18/178 (10.11%)  9/76 (11.84%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  25/178 (14.04%)  9/76 (11.84%) 
Hypoalbuminaemia † 1  9/178 (5.06%)  4/76 (5.26%) 
Hypokalaemia † 1  11/178 (6.18%)  3/76 (3.95%) 
Hypomagnesaemia † 1  10/178 (5.62%)  1/76 (1.32%) 
Hyponatraemia † 1  9/178 (5.06%)  2/76 (2.63%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  12/178 (6.74%)  5/76 (6.58%) 
Back pain † 1  16/178 (8.99%)  3/76 (3.95%) 
Muscle spasms † 1  11/178 (6.18%)  0/76 (0.00%) 
Muscular weakness † 1  2/178 (1.12%)  4/76 (5.26%) 
Myalgia † 1  9/178 (5.06%)  2/76 (2.63%) 
Pain in extremity † 1  8/178 (4.49%)  6/76 (7.89%) 
Nervous system disorders     
Dizziness † 1  23/178 (12.92%)  6/76 (7.89%) 
Dysgeusia † 1  21/178 (11.80%)  6/76 (7.89%) 
Headache † 1  28/178 (15.73%)  9/76 (11.84%) 
Neuropathy peripheral † 1  5/178 (2.81%)  8/76 (10.53%) 
Paraesthesia † 1  6/178 (3.37%)  5/76 (6.58%) 
Psychiatric disorders     
Anxiety † 1  4/178 (2.25%)  6/76 (7.89%) 
Insomnia † 1  17/178 (9.55%)  5/76 (6.58%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  15/178 (8.43%)  10/76 (13.16%) 
Dyspnoea † 1  22/178 (12.36%)  8/76 (10.53%) 
Epistaxis † 1  0/178 (0.00%)  5/76 (6.58%) 
Skin and subcutaneous tissue disorders     
Alopecia † 1  11/178 (6.18%)  12/76 (15.79%) 
Dry skin † 1  0/178 (0.00%)  4/76 (5.26%) 
Erythema † 1  1/178 (0.56%)  4/76 (5.26%) 
Nail discolouration † 1  0/178 (0.00%)  4/76 (5.26%) 
Nail disorder † 1  1/178 (0.56%)  7/76 (9.21%) 
Palmar-plantar erythrodysaesthesia syndrome † 1  1/178 (0.56%)  27/76 (35.53%) 
Pruritus † 1  5/178 (2.81%)  5/76 (6.58%) 
Rash † 1  13/178 (7.30%)  9/76 (11.84%) 
Rash maculo-papular † 1  1/178 (0.56%)  4/76 (5.26%) 
Skin hyperpigmentation † 1  1/178 (0.56%)  4/76 (5.26%) 
1
Term from vocabulary, MedDRA 21.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Leader
Organization: AstraZeneca AB
Phone: 1-877-240-9479
EMail: ClinicalTrialTransparency@astrazeneca.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02282020    
Other Study ID Numbers: D0816C00010
First Submitted: October 20, 2014
First Posted: November 4, 2014
Results First Submitted: October 3, 2019
Results First Posted: December 2, 2019
Last Update Posted: October 28, 2020