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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
British Columbia Cancer Agency
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00679783
First received: May 15, 2008
Last updated: September 2, 2014
Last verified: September 2014
Results First Received: July 19, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: 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  
Number of Participants  
[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  
Gender  
[units: Participants]
               
Female     4     13     3     44     5     5     16     90  
Male     0     0     0     0     0     0     0     0  



  Outcome Measures
  Show All Outcome Measures

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. ]

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

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. ]

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. ]

5.  Secondary:   CA-125 Levels (Ovarian Cancer Patients Only)   [ Time Frame: 24 weeks ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title CA-125 Levels (Ovarian Cancer Patients Only)
Measure Description A response according to CA-125 has occurred if there is at least a 50% reduction in CA-125 levels from a pre-treatment sample.
Time Frame 24 weeks  
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.
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  
Number of Participants Analyzed  
[units: participants]
  4     12     3     35     0     0     0  
CA-125 Levels (Ovarian Cancer Patients Only)  
[units: Percentage¬†of¬†participants]
Number ( 95% Confidence Interval )
  75  
  ( 30.06 to 95.44 )  
  33.33  
  ( 13.81 to 60.94 )  
  0  
  ( 0 to 56.15 )  
  28.57  
  ( 16.33 to 45.05 )  
   
   
   
   
   
   

No statistical analysis provided for CA-125 Levels (Ovarian Cancer Patients Only)



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. ]


  Serious Adverse Events


  Other Adverse Events


  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