Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT00753545
• Recruitment Status: Completed
• First Posted: September 16, 2008
• Results First Posted: March 11, 2013
• Last Update Posted: March 21, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Ovarian Cancer
• Interventions: Drug: AZD2281; Drug: matching placebo
• Enrollment: 265

Participant Flow

Recruitment Details	The first patient was enrolled on 28 August 2008 and the last patient was enrolled on 9 February 2010. Patients were enrolled at 82 centres in 16 countries. Of the 326 patients enrolled, 265 were randomized
Pre-assignment Details	It was planned that 250 women with advanced platinum sensitive serous ovarian cancer who had received 2 or more previous platinum-containing regimens and demonstrated an objective stable maintained response in the last platinum regimen prior to enrolment were to receive olaparib 400 mg bd or matching placebo in a 1:1 ratio. 265 randomised.

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Period Title: Overall Study
Started	136 [1]	129 [1]
Completed	28 [2]	11 [2]
Not Completed	108	118
Reason Not Completed
Death	98	112
Lost to Follow-up	2	3
Protocol Violation	1	0
Voluntary Discontinuation of Patient	7	3
[1] Patients randomized; [2] Patients completing the Study

Baseline Characteristics

Arm/Group Title		Olaparib 400 mg bd	Placebo bd	Total
Arm/Group Description		AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily	Total of all reporting groups
Overall Number of Baseline Participants		136	129	265
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	136 participants	129 participants	265 participants
		58.9 (10.95)	58.5 (9.89)	58.7 (10.43)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	129 participants	265 participants
	Female	136 100.0%	129 100.0%	265 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Time to progression [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	136 participants	129 participants	265 participants
>6 to 12 months		53	54	107
>12 months		83	75	158
		[1] Measure Description: The time to disease progression from the completion of the penultimate platinum containing therapy (last dose) prior to enrolment on the study.
Objective response [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	136 participants	129 participants	265 participants
Complete response		57	63	120
Partial response		79	66	145
		[1] Measure Description: Objective response to the last platinum containing regimen prior to enrolment on the study: CR-Complete Response (defined as normal radiological findings and CA-125 within the normal range); PR-Partial Response (defined as a RECIST PR and/or GCIG CA-125 response)

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) (According to Response Evaluation Criteria in Solid Tumours [RECIST])
Description	PFS was defined as the time from randomisation to the earlier date of radiological progression (per RECIST criteria) or death by any cause in the absence of objective progression. [Full analysis set (FAS)]
Time Frame	Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	136	129
Median (95% Confidence Interval); Unit of Measure: Months
	8.4; (7.4 to 11.5)	4.8; (4.0 to 5.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 400 mg bd, Placebo bd
	Comments	HR < 1 favours olaparib
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.00001
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	The model includes factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.49
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS = time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date patient was known to be alive.
Time Frame	Follow up every 12 weeks post progression, assessed maximum up to 90 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	136	129
Median (95% Confidence Interval); Unit of Measure: Months
	29.8; (26.9 to 35.7)	27.8; (24.9 to 33.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 400 mg bd, Placebo bd
	Comments	HR < 1 favours olaparib
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.02
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	The model includes factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.55 to 0.95
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Objective Response Rate (ORR) (According to RECIST)
Description	For each treatment group, the ORR was the number of Complete Response (CR) and Partial Response (PR) divided by the number of patients in the group in the FAS with measurable disease at baseline (displayed as a percentage below). Evaluable for response set
Time Frame	Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

Evaluable for response set - A subset of the full analysis set which includes patients with measurable disease at baseline

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	57	48
Measure Type: Number; Unit of Measure: percentage of participants
	12.3	4.2

4. Secondary Outcome

Title	Disease Control Rate
Description	Disease control rate was defined as the percentage of patients who have at least 1 confirmed visit response of CR or PR or have demonstrated SD or NED for at least 23 weeks (ie, 24 weeks +/- 1 week) prior to any evidence of progression. [FAS]
Time Frame	Assessed at 24 weeks. Radiologic scans performed at baseline, week 12 (+/- 1 week) and week 24 (+/- 1 week).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	136	129
Measure Type: Number; Unit of Measure: percentage of participants
	53.7	25.6

5. Secondary Outcome

Title	Duration of Response
Description	Duration of response = time from assessment prior to timepoint where PR or CR confirmed (i.e. initial assessment of PR/CR), until earliest date of objective progression or death. [Responding patients only]. There were insufficient responses to enable conclusions to be drawn.
Time Frame	Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	136	129
Median (95% Confidence Interval); Unit of Measure: Months
	4.2; (2.8 to 5.6)	2.3; (1.8 to 2.8)

6. Secondary Outcome

Title	Percentage Change From Baseline in Tumour Size at Week 24
Description	Percentage change from baseline to Week 24 in target tumour size.
Time Frame	Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

Evaluable for response set - A subset of the full analysis set which includes patients with measurable disease at baseline.

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	56	47
Least Squares Mean (Full Range); Unit of Measure: Percent change in tumour size
	-0.8; (-100.0 to 45.0)	26.4; (-36.4 to 39.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 400 mg bd, Placebo bd
	Comments	LS mean < 0 favours olaparib
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.03185
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	The model includes factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy.
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	-27.1
	Confidence Interval	(2-Sided) 95%; -51.9 to -2.4
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Best Percentage Change in Cancer Antigen 125 (CA-125) Levels
Description	Best percentage change from baseline in CA-125 level
Time Frame	CA-125 was measured at baseline then every 28 days on treatment, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

A subset of the FAS with baseline and at least 1 follow-up value of CA-125

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	135	128
Median (Full Range); Unit of Measure: percentage of change
	-16.67; (-100.00 to 346.15)	0.00; (-99.50 to 1436.84)

8. Secondary Outcome

Title	Best Objective Response
Description	Best overall response from radiologic assessments. [FAS]
Time Frame	Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	136	129
Measure Type: Number; Unit of Measure: Participants
Complete Response	0	0
Partial Response	7	2
No evidence of disease	49	42
Stable Disease >= 11 weeks	46	25
Disease Progression	24	55
Not Evaluable	10	5

9. Secondary Outcome

Title	RECIST and CA-125 Response Separately and Combined
Description	RECIST and CA-125 response separately and combined [Patients evaluable for either CA-125 response or RECIST response]
Time Frame	Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter and monthly for CA-125 measurements, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	61	53
Measure Type: Number; Unit of Measure: Participants
RECIST Response	16	2
Confirmed RECIST Response	7	2
Unconfirmed RECIST response	9	0
CA-125 Response	1	1
Confirmed RECIST or CA-125 Response	8	3

10. Secondary Outcome

Title	Time to Earlier of CA-125 or RECIST Progression
Description	Time from randomisation to the earlier date of radiological progression (per RECIST criteria) or CA-125 or death by any cause in the absence of objective progression. [FAS]
Time Frame	Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter and monthly for CA-125 measurements, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	136	129
Median (95% Confidence Interval); Unit of Measure: Months
	8.3; (5.5 to 10.3)	3.7; (2.8 to 4.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 400 mg bd, Placebo bd
	Comments	HR < 1 favours olaparib
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.00001
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	The model includes factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.47
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Improvement Rate for FACT-O Symptom Index (FOSI)
Description	The percentage of patients with an improvement in FOSI. Improvement was defined as a change from baseline of greater than or equal to +3. [Evaluable for FOSI set]
Time Frame	Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

Evaluable for FOSI set - A subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	117	115
Measure Type: Number; Unit of Measure: percentage of evaluable participants
	17.1	14.8

12. Secondary Outcome

Title	Improvement Rate for Trial Outcome Index (TOI)
Description	The percentage of patients with an improvement in TOI. Improvement was defined as a change from baseline of greater than or equal to +7. [Evaluable for TOI set]
Time Frame	Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

Evaluable for TOI - a subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	115	111
Measure Type: Number; Unit of Measure: percentage of evaluable participants
	20.0	18.0

13. Secondary Outcome

Title	Improvement Rate for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)
Description	The percentage of patients with an improvement in total FACT-O. Improvement was defined as a change from baseline of greater than or equal to +9. [Evaluable for FACT-O set]
Time Frame	Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

Evaluable for Total Fact-O set - A subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	114	111
Measure Type: Number; Unit of Measure: percentage of evaluable participants
	21.1	18.9

14. Secondary Outcome

Title	FACT-O Symptom Index (FOSI) Time to Worsening
Description	The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for FOSI set]
Time Frame	Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	117	115
Median (95% Confidence Interval); Unit of Measure: Months
	2.8; (1.8 to 3.7)	3.7; (3.3 to 5.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 400 mg bd, Placebo bd
	Comments	HR < 1 favours olaparib
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.22
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	The model includes factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.71
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Trial Outcome Index(TOI)Time to Worsening
Description	The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for TOI set]
Time Frame	Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	115	111
Median (95% Confidence Interval); Unit of Measure: Months
	3.8; (2.8 to 7.4)	4.6; (3.7 to 7.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 400 mg bd, Placebo bd
	Comments	HR < 1 favours olaparib
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.67
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	The model includes factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.56
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Functional Analysis of Cancer Therapy - Ovarian (FACT-O) Time to Worsening
Description	The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for FACT-O set]
Time Frame	Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib 400 mg bd	Placebo bd
Arm/Group Description:	AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily	olaparib matching placebo oral capsules twice daily
Overall Number of Participants Analyzed	114	111
Median (95% Confidence Interval); Unit of Measure: Months
	2.8; (1.9 to 4.7)	4.6; (3.6 to 5.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olaparib 400 mg bd, Placebo bd
	Comments	HR < 1 favours olaparib
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.38
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	The model includes factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.64
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	128 participants in Placebo as 1 participant withdrew consent prior to treatment
Arm/Group Title	Olaparib 400 mg bd		Placebo
Arm/Group Description	[Not Specified]		[Not Specified]
All-Cause Mortality
	Olaparib 400 mg bd		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Olaparib 400 mg bd		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/136 (22.79%)		11/128 (8.59%)
Blood and lymphatic system disorders
ANAEMIA † 1	3/136 (2.21%)	3	0/128 (0.00%)	0
PANCYTOPENIA † 1	2/136 (1.47%)	2	0/128 (0.00%)	0
THROMBOCYTOPENIA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Cardiac disorders
CARDIOVASCULAR INSUFFICIENCY † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Gastrointestinal disorders
ABDOMINAL INCARCERATED HERNIA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
ABDOMINAL PAIN † 1	0/136 (0.00%)	0	1/128 (0.78%)	2
CONSTIPATION † 1	2/136 (1.47%)	2	0/128 (0.00%)	0
DIARRHOEA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
GASTRITIS † 1	0/136 (0.00%)	0	2/128 (1.56%)	2
IMPAIRED GASTRIC EMPTYING † 1	0/136 (0.00%)	0	1/128 (0.78%)	1
INTESTINAL OBSTRUCTION † 1	1/136 (0.74%)	1	1/128 (0.78%)	1
INTRA-ABDOMINAL HAEMORRHAGE † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
MELAENA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
NAUSEA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
SMALL INTESTINAL OBSTRUCTION † 1	2/136 (1.47%)	2	3/128 (2.34%)	4
VOMITING † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
General disorders
HERNIA PAIN † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
NON-CARDIAC CHEST PAIN † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
PYREXIA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Immune system disorders
IODINE ALLERGY † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Infections and infestations
APPENDICITIS † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
ENDOPHTHALMITIS † 1	0/136 (0.00%)	0	1/128 (0.78%)	1
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE † 1	0/136 (0.00%)	0	1/128 (0.78%)	1
INFLUENZA † 1	0/136 (0.00%)	0	1/128 (0.78%)	1
LIVER ABSCESS † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
PNEUMONIA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
UPPER RESPIRATORY TRACT INFECTION † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
URINARY TRACT INFECTION † 1	1/136 (0.74%)	1	1/128 (0.78%)	1
Injury, poisoning and procedural complications
FEMUR FRACTURE † 1	2/136 (1.47%)	2	0/128 (0.00%)	0
HIP FRACTURE † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
POST PROCEDURAL HAEMATOMA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Metabolism and nutrition disorders
DEHYDRATION † 1	0/136 (0.00%)	0	1/128 (0.78%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
BACK PAIN † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
OSTEOPOROSIS † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE LEUKAEMIA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
BLADDER CANCER † 1	0/136 (0.00%)	0	1/128 (0.78%)	1
INTRADUCTAL PROLIFERATIVE BREAST LESION † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
PAPILLARY THYROID CANCER † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
SQUAMOUS CELL CARCINOMA OF THE ORAL CAVITY † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Nervous system disorders
APHASIA † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
HAEMORRHAGIC STROKE † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
SYNCOPE † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Psychiatric disorders
CONFUSIONAL STATE † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
ASTHMA † 1	0/136 (0.00%)	0	1/128 (0.78%)	1
BRONCHIECTASIS † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
COUGH † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
DYSPNOEA † 1	2/136 (1.47%)	2	0/128 (0.00%)	0
PULMONARY EMBOLISM † 1	1/136 (0.74%)	2	0/128 (0.00%)	0
Vascular disorders
DEEP VEIN THROMBOSIS † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
ESSENTIAL HYPERTENSION † 1	0/136 (0.00%)	0	1/128 (0.78%)	1
VENA CAVA THROMBOSIS † 1	1/136 (0.74%)	1	0/128 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 19.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Olaparib 400 mg bd		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	129/136 (94.85%)		111/128 (86.72%)
Blood and lymphatic system disorders
ANAEMIA † 1	26/136 (19.12%)	32	7/128 (5.47%)	8
NEUTROPENIA † 1	7/136 (5.15%)	8	5/128 (3.91%)	7
Gastrointestinal disorders
ABDOMINAL DISCOMFORT † 1	6/136 (4.41%)	7	7/128 (5.47%)	7
ABDOMINAL DISTENSION † 1	21/136 (15.44%)	24	11/128 (8.59%)	13
ABDOMINAL PAIN † 1	35/136 (25.74%)	44	34/128 (26.56%)	51
ABDOMINAL PAIN LOWER † 1	7/136 (5.15%)	7	10/128 (7.81%)	10
ABDOMINAL PAIN UPPER † 1	25/136 (18.38%)	28	11/128 (8.59%)	11
CONSTIPATION † 1	30/136 (22.06%)	41	14/128 (10.94%)	15
DIARRHOEA † 1	36/136 (26.47%)	62	31/128 (24.22%)	39
DYSPEPSIA † 1	27/136 (19.85%)	34	11/128 (8.59%)	11
NAUSEA † 1	96/136 (70.59%)	128	46/128 (35.94%)	58
STOMATITIS † 1	12/136 (8.82%)	15	4/128 (3.13%)	4
VOMITING † 1	47/136 (34.56%)	91	18/128 (14.06%)	20
General disorders
ASTHENIA † 1	19/136 (13.97%)	26	12/128 (9.38%)	15
FATIGUE † 1	73/136 (53.68%)	92	50/128 (39.06%)	57
OEDEMA PERIPHERAL † 1	12/136 (8.82%)	14	6/128 (4.69%)	7
PYREXIA † 1	13/136 (9.56%)	16	4/128 (3.13%)	4
Infections and infestations
NASOPHARYNGITIS † 1	21/136 (15.44%)	26	14/128 (10.94%)	17
UPPER RESPIRATORY TRACT INFECTION † 1	18/136 (13.24%)	24	8/128 (6.25%)	8
URINARY TRACT INFECTION † 1	15/136 (11.03%)	21	6/128 (4.69%)	6
Investigations
BLOOD CREATININE INCREASED † 1	9/136 (6.62%)	10	2/128 (1.56%)	2
Metabolism and nutrition disorders
DECREASED APPETITE † 1	29/136 (21.32%)	34	17/128 (13.28%)	22
HYPOMAGNESAEMIA † 1	8/136 (5.88%)	10	9/128 (7.03%)	10
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	24/136 (17.65%)	36	18/128 (14.06%)	19
BACK PAIN † 1	25/136 (18.38%)	37	14/128 (10.94%)	16
MUSCLE SPASMS † 1	13/136 (9.56%)	20	5/128 (3.91%)	5
MUSCULOSKELETAL PAIN † 1	10/136 (7.35%)	10	8/128 (6.25%)	8
MYALGIA † 1	7/136 (5.15%)	7	8/128 (6.25%)	9
PAIN IN EXTREMITY † 1	12/136 (8.82%)	16	7/128 (5.47%)	8
Nervous system disorders
DIZZINESS † 1	21/136 (15.44%)	28	9/128 (7.03%)	10
DYSGEUSIA † 1	22/136 (16.18%)	26	8/128 (6.25%)	8
HEADACHE † 1	29/136 (21.32%)	47	17/128 (13.28%)	20
NEUROPATHY PERIPHERAL † 1	12/136 (8.82%)	13	3/128 (2.34%)	5
PARAESTHESIA † 1	7/136 (5.15%)	9	3/128 (2.34%)	5
Psychiatric disorders
ANXIETY † 1	8/136 (5.88%)	8	5/128 (3.91%)	6
DEPRESSION † 1	11/136 (8.09%)	11	9/128 (7.03%)	10
INSOMNIA † 1	9/136 (6.62%)	9	9/128 (7.03%)	10
Respiratory, thoracic and mediastinal disorders
COUGH † 1	23/136 (16.91%)	33	13/128 (10.16%)	14
DYSPNOEA † 1	17/136 (12.50%)	20	8/128 (6.25%)	8
Skin and subcutaneous tissue disorders
DRY SKIN † 1	3/136 (2.21%)	3	7/128 (5.47%)	7
PRURITUS † 1	8/136 (5.88%)	10	3/128 (2.34%)	3
RASH † 1	8/136 (5.88%)	8	12/128 (9.38%)	13
Vascular disorders
HOT FLUSH † 1	5/136 (3.68%)	6	16/128 (12.50%)	18
HYPERTENSION † 1	10/136 (7.35%)	10	4/128 (3.13%)	4
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 19.0

Limitations and Caveats

For OM DoR: The subset of patients evaluable for response who responded to study treatment.Values in results table may be under-estimates as some patients had not progressed at final analysis,so true duration is likely to be greater than in database.

More Information

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.

Results Point of Contact

• Name/Title: Global Clinical Lead
• Organization: AstraZeneca
• Phone: 1-877-240-9479
• EMail: information.center@astrazeneca.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.

Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Bennett B, Parry D, Spencer S, Mann H, Matulonis U. Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer. Br J Cancer. 2016 Nov 22;115(11):1313-1320. doi: 10.1038/bjc.2016.348. Epub 2016 Nov 8.

Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. doi: 10.1016/S1470-2045(16)30376-X. Epub 2016 Sep 9.

Matulonis UA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Parry D, Grinsted L, Ledermann JA. Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation: Overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy. Cancer. 2016 Jun 15;122(12):1844-52. doi: 10.1002/cncr.29995. Epub 2016 Apr 8.

Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Dougherty B, Orr M, Hodgson D, Barrett JC, Matulonis U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014 Jul;15(8):852-61. doi: 10.1016/S1470-2045(14)70228-1. Epub 2014 May 31. Erratum In: Lancet Oncol. 2015 Apr;16(4):e158.

Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. doi: 10.1056/NEJMoa1105535. Epub 2012 Mar 27.

Yap TA, Carden CP, Kaye SB. Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer. 2009 Mar;9(3):167-81. doi: 10.1038/nrc2583.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00753545
• Other Study ID Numbers: D0810C00019; 2008-003439-18 ( EudraCT Number )
• First Submitted: September 12, 2008
• First Posted: September 16, 2008
• Results First Submitted: December 7, 2012
• Results First Posted: March 11, 2013
• Last Update Posted: March 21, 2024