Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men with Metastatic Castration-Resistant Prostate Cancer (PROfound Study)

Study identifier:D081DC00007

ClinicalTrials.gov identifier:NCT02987543

EudraCT identifier:2016-000300-28

CTIS identifier:N/A

Study Complete

Official Title

A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men with Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment with a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations (PROfound)

Medical condition

metastatic castration-resistant prostate cancer

Phase

Phase 3

Healthy volunteers

Study drug

olaparib, enzalutamide, abiraterone acetate

Sex

Male

Actual Enrollment

387

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 06 Feb 2017

Primary Completion Date: 04 Jun 2019

Study Completion Date: 15 Feb 2023

Study design

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

Verification:

Verified 01 Sept 2023 by AstraZeneca

Collaborators

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc, Foundation Medicine, Inc., Myriad Genetics, Inc.

Inclusion and exclusion criteria

Location

Research Site

Atlanta, GA, United States, 30318

Location

Research Site

Wheeling, WV, United States, 26003

Location

Research Site

Tucson, AZ, United States, 85741

Location

Research Site

New Orleans, LA, United States, 70112

Location

Research Site

Salt Lake City, UT, United States, 84112

Location

Research Site

Jeffersonville, IN, United States, 47130

Location

Research Site

Brooklyn, NY, United States, 11201

Location

Research Site

Columbus, OH, United States, 43230

Arms	Assigned Interventions
Experimental: Olaparib Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose of 300 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions	Drug: olaparib 300 mg (2x 150 mg tablets) twice daily Other Name: Lynparza
Active Comparator: Enzalutamide OR abiraterone acetate Enzalutamide: Enzalutamide is available as capsules or tablets containing 40 mg of enzalutamide. Subjects will be administered study treatment orally at a dose of 160 mg once daily. Abiraterone acetate with prednisone: Abiraterone acetate is available as tablets containing 250 mg or 500 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg administered twice daily orally. Prednisolone is permitted for use instead of prednisone if necessary.	Drug: enzalutamide 160 mg (4 x 40 mg capsules) once daily Other Name: XTANDI Drug: abiraterone acetate 1,000 mg (4 x 250 mg tablets) once daily Other Name: ZYTIGA Drug: abiraterone acetate 1,000 mg (2 x 500 mg tablets) once daily Other Name: ZYTIGA Drug: enzalutamide 160 mg (4 x 40 mg tablets) once daily Other Name: XTANDI

Arms

Assigned Interventions

Experimental: Olaparib
Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose of 300 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions

Drug: olaparib
300 mg (2x 150 mg tablets) twice daily

Other Name: Lynparza

Active Comparator: Enzalutamide OR abiraterone acetate
Enzalutamide: Enzalutamide is available as capsules or tablets containing 40 mg of enzalutamide. Subjects will be administered study treatment orally at a dose of 160 mg once daily. Abiraterone acetate with prednisone: Abiraterone acetate is available as tablets containing 250 mg or 500 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg administered twice daily orally. Prednisolone is permitted for use instead of prednisone if necessary.

Drug: enzalutamide
160 mg (4 x 40 mg capsules) once daily

Other Name: XTANDI

Drug: abiraterone acetate
1,000 mg (4 x 250 mg tablets) once daily

Other Name: ZYTIGA

Drug: abiraterone acetate
1,000 mg (2 x 500 mg tablets) once daily

Other Name: ZYTIGA

Drug: enzalutamide
160 mg (4 x 40 mg tablets) once daily

Other Name: XTANDI

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were divided into two cohorts based on HRR gene mutation status. Subjects with mutations in either BRCA1, BRCA2, or ATM are in Cohort A whereas subjects with mutations among 12 other genes involved in the HRR pathway (BARD1, BRIP1, CDK12, CHEK1,CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L) are in Cohort B.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Cohort A Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
Cohort B Olaparib 300mg bd	2x150mg film-coated tablets
Cohort B Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Participant Flow: Overall Study

	Cohort A Olaparib 300mg bd	Cohort A Investigators choice of NHA	Cohort B Olaparib 300mg bd	Cohort B Investigators choice of NHA
STARTED	162	83	94	48
COMPLETED	0	0	0	0
NOT COMPLETED	162	83	94	48
Ongoing study at data cut off	49	21	19	12
Death	88	54	67	28
Lost to Follow-up	3	0	1	0
Screen failure	0	0	0	1
Withdrawal by Subject	21	7	7	6
Study terminated by sponsor	1	0	0	0
Investigator decision	0	1	0	0
Disease progression	0	0	0	1

Baseline Characteristics

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

Reporting Groups

	Description
Cohort A Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
Cohort B Olaparib 300mg bd	2x150mg film-coated tablets
Cohort B Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Baseline Measures

	Cohort A Olaparib 300mg bd	Cohort A Investigators choice of NHA	Cohort B Olaparib 300mg bd	Cohort B Investigators choice of NHA	Total
Number of Participants [units: Participants]	162	83	94	48	387
Age Continuous [units: Years] Mean ± Standard Deviation	68.0 ± 8.23	68.1 ± 7.36	69.2 ± 8.79	70.3 ± 7.83	68.6 ± 8.15
Race/Ethnicity, Customized [units: Participants]
White	109	55	54	30	248
Black or African American	2	1	5	0	8
Asian	43	19	26	17	105
Other	1	1	1	0	3
Missing	7	7	8	1	23
Sex: Female, Male [units: Participants]
Female	0	0	0	0	0
Male	162	83	94	48	387

Outcome Measures

1. Primary Outcome Measure: Radiological Progression Free Survival (rPFS) by blinded independent central review (BICR) - Cohort A only [ Time Frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively). ]

Measure Type	Primary
Measure Name	Radiological Progression Free Survival (rPFS) by blinded independent central review (BICR) - Cohort A only
Measure Description	The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as >= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, >=6 weeks later, must show >=2 more new bone lesions (for a total of >=4 new bone lesions since baseline).
Time Frame	Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
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.
Full Analysis Set

Reporting Groups

	Description
Cohort A Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Measured Values

	Cohort A Olaparib 300mg bd	Cohort A Investigators choice of NHA
Number of Participants Analyzed [units:participants]	162	83
Radiological Progression Free Survival (rPFS) by blinded independent central review (BICR) - Cohort A only [units: Months] Median (95% Confidence Interval)	7.39 (6.24 to 9.33)	3.55 (1.91 to 3.71)

Statistical Analysis 1 for Radiological Progression Free Survival (rPFS) by blinded independent central review (BICR) - Cohort A only

Groups^[1]	All groups
Method^[3]	Regression, Cox
P-Value^[4]	<0.0001
Hazard Ratio (HR)^[5]	0.34
95% Confidence Interval	( 0.25 to 0.47 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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:
	No text entered.

2. Secondary Outcome Measure: Confirmed Objective Response Rate (ORR) by blinded independent central review (BICR) - Cohort A only [ Time Frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively). ]

Measure Type	Secondary
Measure Name	Confirmed Objective Response Rate (ORR) by blinded independent central review (BICR) - Cohort A only
Measure Description	ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = >=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.
Time Frame	Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
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 response

Reporting Groups

	Description
Cohort A Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Measured Values

	Cohort A Olaparib 300mg bd	Cohort A Investigators choice of NHA
Number of Participants Analyzed [units:participants]	84	43
Confirmed Objective Response Rate (ORR) by blinded independent central review (BICR) - Cohort A only [units: Participants]
Response	28	1
No response	56	42

Statistical Analysis 1 for Confirmed Objective Response Rate (ORR) by blinded independent central review (BICR) - Cohort A only

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	<0.0001
Odds Ratio (OR)^[5]	20.86
95% Confidence Interval	( 4.18 to 379.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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:
	No text entered.

3. Secondary Outcome Measure: Radiological Progression Free Survival (rPFS) by blinded independent central review (BICR) - Cohort A+B [ Time Frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively). ]

Measure Type	Secondary
Measure Name	Radiological Progression Free Survival (rPFS) by blinded independent central review (BICR) - Cohort A+B
Measure Description	The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
Time Frame	Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
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.
Full Analysis Set

Reporting Groups

	Description
Cohort A Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Measured Values

	Cohort A Olaparib 300mg bd	Cohort A Investigators choice of NHA
Number of Participants Analyzed [units:participants]	256	131
Radiological Progression Free Survival (rPFS) by blinded independent central review (BICR) - Cohort A+B [units: Months] Median (95% Confidence Interval)	5.82 (5.52 to 7.36)	3.52 (2.2 to 3.65)

Statistical Analysis 1 for Radiological Progression Free Survival (rPFS) by blinded independent central review (BICR) - Cohort A+B

Groups^[1]	All groups
Method^[3]	Regression, Cox
P-Value^[4]	<0.0001
Hazard Ratio (HR)^[5]	0.49
95% Confidence Interval	( 0.38 to 0.63 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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:
	No text entered.

4. Secondary Outcome Measure: Time to pain progression - Cohort A only [ Time Frame: Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively). ]

Measure Type	Secondary
Measure Name	Time to pain progression - Cohort A only
Measure Description	Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.
Time Frame	Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
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.
Full Analysis Set

Reporting Groups

	Description
Cohort A Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Measured Values

	Cohort A Olaparib 300mg bd	Cohort A Investigators choice of NHA
Number of Participants Analyzed [units:participants]	162	83
Time to pain progression - Cohort A only [units: Months] Median (95% Confidence Interval)	NA (NA to NA) ^[1]	9.92 (5.39 to NA) ^[1]

Statistical Analysis 1 for Time to pain progression - Cohort A only

Groups^[1]	All groups
Method^[3]	Regression, Cox
P-Value^[4]	0.0192
Hazard Ratio (HR)^[5]	0.44
95% Confidence Interval	( 0.22 to 0.91 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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:
	No text entered.

5. Secondary Outcome Measure: Overall Survival (OS) - Cohort A only [ Time Frame: Approximately 35 months after the first patient was randomised. ]

Measure Type	Secondary
Measure Name	Overall Survival (OS) - Cohort A only
Measure Description	Number of Participants with Overall Survival (OS) - Cohort A only.
Time Frame	Approximately 35 months after the first patient was randomised.
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.
Full analysis set

Reporting Groups

	Description
Cohort A Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Measured Values

	Cohort A Olaparib 300mg bd	Cohort A Investigators choice of NHA
Number of Participants Analyzed [units:participants]	162	83
Overall Survival (OS) - Cohort A only [units: Participants]
Died	91	57
Alive at data cut-off	49	21
Terminated prior to death (withdrawn consent)	22	5

Statistical Analysis 1 for Overall Survival (OS) - Cohort A only

Groups^[1]	All groups
Method^[3]	Regression, Cox
P-Value^[4]	0.0175
Hazard Ratio (HR)^[5]	0.69
95% Confidence Interval	( 0.50 to 0.97 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[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:
	No text entered.

Serious Adverse Events

Time Frame	From the time of signature of informed consent throughout the treatment period (median duration of treatment of 7.5 and 3.9 months for Olaparib and Investigators Choice of NHA respectively) up to and including the 30-day follow-up period
Additional Description	There were 131 subjects randomised to the Investigators Choice of NHA treatment group (Full Analysis Set), however 1 of these subjects did not receive treatment (resulting in 130 in the Safety Analysis Set). Hence, for the Investigators Choice of NHA, the Total number at risk for all-cause mortality = 131 while the Total # at Risk by any Serious Adverse Event = 130 and the Total # at Risk by any Other Adverse Event = 130.

Time Frame

From the time of signature of informed consent throughout the treatment period (median duration of treatment of 7.5 and 3.9 months for Olaparib and Investigators Choice of NHA respectively) up to and including the 30-day follow-up period

Additional Description

There were 131 subjects randomised to the Investigators Choice of NHA treatment group (Full Analysis Set), however 1 of these subjects did not receive treatment (resulting in 130 in the Safety Analysis Set). Hence, for the Investigators Choice of NHA, the Total number at risk for all-cause mortality = 131 while the Total # at Risk by any Serious Adverse Event = 130 and the Total # at Risk by any Other Adverse Event = 130.

Reporting Groups

	Description
Cohort A+B Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A+B Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Serious Adverse Events

Cohort A+B Olaparib 300mg bd

Cohort A+B Investigators choice of NHA

Total, serious adverse events

# participants affected / at risk

94/256 (36.72%)

39/130 (30.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

23/256 (8.98%)

0/130 (0.00%)

# events

Blood and lymphatic system disorders

Febrile neutropenia¹,^†

# participants affected / at risk

1/256 (0.39%)

1/130 (0.77%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

3/256 (1.17%)

0/130 (0.00%)

# events

Blood and lymphatic system disorders

Pancytopenia¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

4/256 (1.56%)

0/130 (0.00%)

# events

Cardiac disorders

Acute coronary syndrome¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

1/256 (0.39%)

2/130 (1.54%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Cardiac disorders

Cardiac failure acute¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Cardiac disorders

Cardiomyopathy¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Cardiac disorders

Cardiopulmonary failure¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

Cardiac disorders

Coronary ostial stenosis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Cardiac disorders

Right ventricular failure¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Endocrine disorders

Adrenal insufficiency¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Eye disorders

Diplopia¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Gastrointestinal disorders

Diverticulum intestinal¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Gastrointestinal disorders

Gastric perforation¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Gastrointestinal disorders

Gastric ulcer¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Gastrointestinal disorders

Gastric ulcer haemorrhage¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Gastrointestinal disorders

Inguinal hernia¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/256 (0.78%)

2/130 (1.54%)

# events

Gastrointestinal disorders

Obstruction gastric¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Gastrointestinal disorders

Obstructive pancreatitis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Gastrointestinal disorders

Small intestinal obstruction¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Gastrointestinal disorders

Stress ulcer¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

4/256 (1.56%)

1/130 (0.77%)

# events

General disorders

Asthenia¹,^†

# participants affected / at risk

4/256 (1.56%)

1/130 (0.77%)

# events

General disorders

Death¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

General disorders

General physical health deterioration¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

General disorders

Pain¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

General disorders

Pyrexia¹,^†

# participants affected / at risk

3/256 (1.17%)

2/130 (1.54%)

# events

General disorders

Sudden death¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Hepatobiliary disorders

Budd-Chiari syndrome¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Hepatobiliary disorders

Cholangitis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Hepatobiliary disorders

Cholecystitis acute¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Infections and infestations

Anal abscess¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Infections and infestations

Cellulitis of male external genital organ¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Infections and infestations

Cystitis¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Infections and infestations

Infection¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Infections and infestations

Neutropenic sepsis¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

11/256 (4.30%)

4/130 (3.08%)

# events

Infections and infestations

Pyelonephritis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

3/256 (1.17%)

3/130 (2.31%)

# events

Infections and infestations

Septic shock¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

5/256 (1.95%)

4/130 (3.08%)

# events

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Injury, poisoning and procedural complications

Ankle fracture¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Concussion¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Cystitis radiation¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

1/256 (0.39%)

2/130 (1.54%)

# events

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

3/256 (1.17%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Fracture¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Gastroenteritis radiation¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Post-traumatic pain¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Spinal compression fracture¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Spinal fracture¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

Injury, poisoning and procedural complications

Subdural haematoma¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/256 (0.00%)

3/130 (2.31%)

# events

Metabolism and nutrition disorders

Hypocalcaemia¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Metabolism and nutrition disorders

Hypoglycaemia¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

1/256 (0.39%)

1/130 (0.77%)

# events

Musculoskeletal and connective tissue disorders

Bone pain¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

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

Gastric cancer¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

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

Glioma¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

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

Transitional cell carcinoma¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Nervous system disorders

Ballismus¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Nervous system disorders

Cerebral infarction¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

3/256 (1.17%)

0/130 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Nervous system disorders

Ischaemic stroke¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Nervous system disorders

Neuralgia¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Nervous system disorders

Spinal cord compression¹,^†

# participants affected / at risk

1/256 (0.39%)

1/130 (0.77%)

# events

Psychiatric disorders

Confusional state¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Psychiatric disorders

Delirium¹,^†

# participants affected / at risk

1/256 (0.39%)

2/130 (1.54%)

# events

Musculoskeletal and connective tissue disorders

Spinal stenosis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

1/256 (0.39%)

2/130 (1.54%)

# events

Renal and urinary disorders

Calculus bladder¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Renal and urinary disorders

Chronic kidney disease¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

3/256 (1.17%)

1/130 (0.77%)

# events

Renal and urinary disorders

Hydronephrosis¹,^†

# participants affected / at risk

1/256 (0.39%)

1/130 (0.77%)

# events

Renal and urinary disorders

Nephrolithiasis¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Renal and urinary disorders

Renal failure¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Renal and urinary disorders

Renal impairment¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Renal and urinary disorders

Urinary retention¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

Renal and urinary disorders

Urinary tract obstruction¹,^†

# participants affected / at risk

0/256 (0.00%)

2/130 (1.54%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

4/256 (1.56%)

1/130 (0.77%)

# events

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration¹,^†

# participants affected / at risk

3/256 (1.17%)

0/130 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

2/256 (0.78%)

0/130 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

5/256 (1.95%)

1/130 (0.77%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Skin and subcutaneous tissue disorders

Drug eruption¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Vascular disorders

Arterial thrombosis¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Vascular disorders

Embolism¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Vascular disorders

Orthostatic hypotension¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Vascular disorders

Phlebitis¹,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Cardiac disorders

Coronary artery stenosis²,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Gastrointestinal disorders

Duodenal ulcer perforation²,^†

# participants affected / at risk

0/256 (0.00%)

1/130 (0.77%)

# events

Infections and infestations

Pneumocystis jirovecii pneumoni²,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Nervous system disorders

Syncope²,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

Skin and subcutaneous tissue disorders

Skin ulcer²,^†

# participants affected / at risk

1/256 (0.39%)

0/130 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 22.0
2	Term from vocabulary, MedDRA 22.1

Other Adverse Events

Time Frame	From the time of signature of informed consent throughout the treatment period (median duration of treatment of 7.5 and 3.9 months for Olaparib and Investigators Choice of NHA respectively) up to and including the 30-day follow-up period
Additional Description	There were 131 subjects randomised to the Investigators Choice of NHA treatment group (Full Analysis Set), however 1 of these subjects did not receive treatment (resulting in 130 in the Safety Analysis Set). Hence, for the Investigators Choice of NHA, the Total number at risk for all-cause mortality = 131 while the Total # at Risk by any Serious Adverse Event = 130 and the Total # at Risk by any Other Adverse Event = 130.

Time Frame

Additional Description

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Cohort A+B Olaparib 300mg bd	2x150mg film-coated tablets
Cohort A+B Investigators choice of NHA	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)

Other Adverse Events

Cohort A+B Olaparib 300mg bd

Cohort A+B Investigators choice of NHA

Total, other (not including serious) adverse events

# participants affected / at risk

241/256 (94.14%)

112/130 (86.15%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

110/256 (42.97%)

20/130 (15.38%)

# events

154

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

49/256 (19.14%)

19/130 (14.62%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

54/256 (21.09%)

9/130 (6.92%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

20/256 (7.81%)

3/130 (2.31%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

109/256 (42.58%)

26/130 (20.00%)

# events

136

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

49/256 (19.14%)

17/130 (13.08%)

# events

General disorders

Asthenia¹,^†

# participants affected / at risk

37/256 (14.45%)

18/130 (13.85%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

68/256 (26.56%)

28/130 (21.54%)

# events

General disorders

Oedema peripheral¹,^†

# participants affected / at risk

34/256 (13.28%)

10/130 (7.69%)

# events

General disorders

Pyrexia¹,^†

# participants affected / at risk

15/256 (5.86%)

4/130 (3.08%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

18/256 (7.03%)

12/130 (9.23%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

21/256 (8.20%)

7/130 (5.38%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

78/256 (30.47%)

24/130 (18.46%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

25/256 (9.77%)

14/130 (10.77%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

36/256 (14.06%)

17/130 (13.08%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

14/256 (5.47%)

6/130 (4.62%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

17/256 (6.64%)

6/130 (4.62%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

17/256 (6.64%)

5/130 (3.85%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

18/256 (7.03%)

2/130 (1.54%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

16/256 (6.25%)

3/130 (2.31%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

14/256 (5.47%)

4/130 (3.08%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

6/256 (2.34%)

10/130 (7.69%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

29/256 (11.33%)

3/130 (2.31%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

24/256 (9.38%)

4/130 (3.08%)

# events

Blood and lymphatic system disorders

Lymphopenia¹,^†

# participants affected / at risk

13/256 (5.08%)

1/130 (0.77%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

13/256 (5.08%)

0/130 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

18/256 (7.03%)

2/130 (1.54%)

# events

Gastrointestinal disorders

Stomatitis²,^†

# participants affected / at risk

13/256 (5.08%)

2/130 (1.54%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity²,^†

# participants affected / at risk

14/256 (5.47%)

6/130 (4.62%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 22.0
2	Term from vocabulary, MedDRA 22.1

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.

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
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca Clinical Study Information Center
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

CSP redacted
Download
redacted SAP
Download
Redacted CSR synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Johann de Bono

The Institute of Cancer Research, United Kingdom

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSP redacted

redacted SAP

Redacted CSR synopsis

Trial Results Summaries