Phase II Study of AZD2281 in Patients With Known BRCA Mutation Status or Recurrent High Grade Ovarian Cancer or Patients With Known BRCA Mutation Status/ Triple Neg Breast Cancer

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions:	Ovarian Carcinoma; Breast Cancer
Intervention:	Drug: AZD2281

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first patient was enrolled on July 8, 2008 and efficacy and safety data were collected up to the data cut-off of March 26, 2010. Patients were enrolled at 6 centres in Canada. Of the 112 patients who gave informed consent 21 patients failed eligibility criteria or withdrew their consent and were not allocated to treatment.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study enrolled both known BRCA mutation carriers and patients with unknown BRCA status. Those with unknown status at entry had to provide a DNA sample for BRCA. One participant in arm 4 discontinued before receiving study drug and is excluded from the safety analysis set mutation analysis. Study data are summarised by confirmed mutation status.

Reporting Groups

	Description
BRCA Positive Non-serous Ovarian	Patients with non-serous ovarian cancer who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. (Serous tumors are the most common subtype of ovarian cancer; other subtypes are grouped together as "non-serous" in this study).
BRCA Positive Serous Ovarian	Patients with serous ovarian cancer who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. (Serous tumors are the most common subtype of ovarian cancer).
BRCA Negative Non-serous Ovarian	Patients with non-serous ovarian cancer who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2
BRCA Negative Serous Ovarian	Patients with serous ovarian cancer who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2
BRCA Positive Non-triple Negative Breast	Patients with non-Triple negative breast cancer (non-TNBC) who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. Non-TNBC are cancers that have receptors for oestrogen, progesterone or Her2
BRCA Positive Triple Negative Breast	Patients with Triple negative breast cancer (TNBC) who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. TNBC are cancers that don’t have receptors for oestrogen, progesterone or Her2 (Some commonly used breast cancer treatments don’t work for TNBC)
BRCA Negative Triple Negative Breast	Patients with Triple negative breast cancer (TNBC) who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2.

Participant Flow:   Overall Study

	BRCA Positive Non-serous Ovarian	BRCA Positive Serous Ovarian	BRCA Negative Non-serous Ovarian	BRCA Negative Serous Ovarian	BRCA Positive Non-triple Negative Breast	BRCA Positive Triple Negative Breast	BRCA Negative Triple Negative Breast
STARTED	4 [1]	13 [1]	3 [1]	45 [1]	5 [1]	5 [1]	16 [1]
COMPLETED	2 [2]	10 [2]	2 [2]	25 [2]	4 [2]	5 [2]	15 [2]
NOT COMPLETED	2	3	1	20	1	0	1
Adverse Event	0	0	0	3	0	0	1
Lack of Efficacy	0	1	0	2	0	0	0
Withdrawal by Subject	0	0	1	1	0	0	0
Not Captured	0	0	0	5	0	0	0
Ongoing at data cut-off	2	2	0	9	1	0	0

[1]	Gave Informed consent and passed screening
[2]	Patients who discontinued treatment following disease progression.

  Baseline Characteristics

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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.
No text entered.

Reporting Groups

	Description
BRCA Positive Non-serous Ovarian	Patients with non-serous ovarian cancer who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. (Serous tumors are the most common subtype of ovarian cancer; other subtypes are grouped together as "non-serous" in this study).
BRCA Positive Serous Ovarian	Patients with serous ovarian cancer who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. (Serous tumors are the most common subtype of ovarian cancer).
BRCA Negative Non-serous Ovarian	Patients with non-serous ovarian cancer who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2
BRCA Negative Serous Ovarian	Patients with serous ovarian cancer who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2
BRCA Positive Non-triple Negative Breast	Patients with non-Triple negative breast cancer (non-TNBC) who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. Non-TNBC are cancers that have receptors for oestrogen, progesterone or Her2
BRCA Positive Triple Negative Breast	Patients with Triple negative breast cancer (TNBC) who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. TNBC are cancers that don’t have receptors for oestrogen, progesterone or Her2 (Some commonly used breast cancer treatments don’t work for TNBC)
BRCA Negative Triple Negative Breast	Patients with Triple negative breast cancer (TNBC) who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2.
Total	Total of all reporting groups

Baseline Measures

	BRCA Positive Non-serous Ovarian	BRCA Positive Serous Ovarian	BRCA Negative Non-serous Ovarian	BRCA Negative Serous Ovarian	BRCA Positive Non-triple Negative Breast	BRCA Positive Triple Negative Breast	BRCA Negative Triple Negative Breast	Total
Overall Participants Analyzed; [Units: Participants]	4	13	3	44	5	5	16	90
Age; [Units: Year]; Mean (Standard Deviation)	60 (18.7)	53.7 (7.3)	60.3 (12.9)	61 (9.5)	49.4 (20.5)	44.8 (15.5)	48.8 (5.5)	52.9 (13)
Sex: Female, Male; [Units: Participants]; Count of Participants
Female	4 100.0%	13 100.0%	3 100.0%	44 100.0%	5 100.0%	5 100.0%	16 100.0%	90 100.0%
Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

  Outcome Measures

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1. Primary:

Objective Response Rate (ORR) Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) Guidelines [ Time Frame: Each patient with measurable disease at baseline was assessed for Objective Response from the sequence of RECIST scan data up to data cut-off, 26 March 2010. RECIST scans were performed every 8 weeks (+/- 2 weeks) from randomization. ]

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2. Secondary:

Disease Control Rate (DCR) [ Time Frame: 16 Weeks ]

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3. Secondary:

Duration of Response [ Time Frame: RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010. ]

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4. Secondary:

Best Percentage Change From Baseline in Tumour Size [ Time Frame: Each patient with measurable disease at baseline was assessed for best percentage change in tumour size from the sequence of RECIST scan data up to data cut-off, 26 March 2010. RECIST scans were performed every 8 weeks (+/- 2 weeks) from randomization. ]

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5. Secondary:

CA-125 Levels (Ovarian Cancer Patients Only) [ Time Frame: 24 weeks ]

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6. Secondary:

Progression Free Survival (PFS) [ Time Frame: RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010. ]

  Hide Outcome Measure 6

Measure Type	Secondary
Measure Title	Progression Free Survival (PFS)
Measure Description	PFS is defined as the time from first dose to the earlier date of radiologic progression (as per Response Evaluation Criteria In Solid Tumours (RECIST) criteria or death by any cause in the absence of objective progression.
Time Frame	RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010.

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.
No text entered.

Reporting Groups

	Description
BRCA Positive Non-serous Ovarian	Patients with non-serous ovarian cancer who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. (Serous tumors are the most common subtype of ovarian cancer; other subtypes are grouped together as "non-serous" in this study).
BRCA Positive Serous Ovarian	Patients with serous ovarian cancer who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. (Serous tumors are the most common subtype of ovarian cancer).
BRCA Negative Non-serous Ovarian	Patients with non-serous ovarian cancer who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2
BRCA Negative Serous Ovarian	Patients with serous ovarian cancer who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2
BRCA Positive Non-triple Negative Breast	Patients with non-Triple negative breast cancer (non-TNBC) who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. Non-TNBC are cancers that have receptors for oestrogen, progesterone or Her2
BRCA Positive Triple Negative Breast	Patients with Triple negative breast cancer (TNBC) who have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2. TNBC are cancers that don’t have receptors for oestrogen, progesterone or Her2 (Some commonly used breast cancer treatments don’t work for TNBC)
BRCA Negative Triple Negative Breast	Patients with Triple negative breast cancer (TNBC) who do not have a harmful mutation in the "breast cancer genes" BRCA1 or BRCA2.

Measured Values

	BRCA Positive Non-serous Ovarian	BRCA Positive Serous Ovarian	BRCA Negative Non-serous Ovarian	BRCA Negative Serous Ovarian	BRCA Positive Non-triple Negative Breast	BRCA Positive Triple Negative Breast	BRCA Negative Triple Negative Breast
Participants Analyzed	4	13	3	44	5	5	16
Progression Free Survival (PFS); [Units: Days]; Median (Full Range)	346.5; (51 to 553)	219; (1 to 503)	79.5; (1 to 109)	192; (1 to 559)	165; (53 to 168)	106; (37 to 277)	54; (1 to 111)

No statistical analysis provided for Progression Free Survival (PFS)

  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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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
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  More Information

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Certain Agreements:  

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

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

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Results Point of Contact:  

Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: aztrial_results_posting@astrazeneca.com

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

Matulonis UA, Penson RT, Domchek SM, Kaufman B, Shapira-Frommer R, Audeh MW, Kaye S, Molife LR, Gelmon KA, Robertson JD, Mann H, Ho TW, Coleman RL. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol. 2016 Jun;27(6):1013-9. doi: 10.1093/annonc/mdw133. Epub 2016 Mar 8.

Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, De Greve J, Atkinson T, Yap TA, Sandhu S, Banerjee S, Chen LM, Friedlander ML, Kaufman B, Oza AM, Matulonis U, Barber LJ, Kozarewa I, Fenwick K, Assiotis I, Campbell J, Chen L, de Bono JS, Gore ME, Lord CJ, Ashworth A, Kaye SB. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013 Oct 1;19(19):5485-93. doi: 10.1158/1078-0432.CCR-13-1262. Epub 2013 Aug 6.

Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, Hirte H, Huntsman D, Clemons M, Gilks B, Yerushalmi R, Macpherson E, Carmichael J, Oza A. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011 Sep;12(9):852-61. doi: 10.1016/S1470-2045(11)70214-5. Epub 2011 Aug 19.

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00679783 History of Changes
Other Study ID Numbers:	D0810C00020
First Submitted:	May 15, 2008
First Posted:	May 19, 2008
Results First Submitted:	July 19, 2011
Results First Posted:	August 12, 2011
Last Update Posted:	June 8, 2018