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 Overview
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Brief Summary
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This is a Phase II, open label, non randomized correlative study of AZD2281 in patients with recurrent breast and ovarian cancer in both BRCA inherited mutation carriers and non-carriers to identify objective response rate and to assess for early markers of activity and to assess correlative markers that may provide helpful information for subsequent clinical trials. Approximately 110 patients from 7 centers in Canada will be enrolled into this study

Official Title
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Phase II, Open Label, Non-Randomized Study of AZD2281 in the Treatment of Patients With Known BRCA or Recurrent High Grade Serous/ Undifferentiated Tubo-Ovarian Carcinoma and in Known BRCA or Triple Negative Breast Cancer to Determine Response Rate and Correlative Markers of Response

Conditions
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Ovarian Carcinoma, Breast Cancer

Intervention / Treatment
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* Drug: AZD2281


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed high grade serous and/or undifferentiated carcinoma of ovary, fallopian tube or peritoneum Oestrogen, progesterone and HER2 negative advanced adenocarcinoma of the breast Known BRCA positive breast cancer or ovarian cancer, that is not high grade serous or undifferentiated tubo-ovarian carcinoma. Performance status of no more than 2. Exclusion Criteria: Any chemotherapy, radiotherapy ( except palliative), endocrine or immunotherapy within 4 weeks prior to entry Major surgery with 4 weeks of entering the study and must have recovered from effects of any major surgery .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 4 parallel arms for the 2 tumour types and the BRCA mutation groups: Triple negative breast Cancer with unknown BRCA mutation status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally Known BRCA mutation positive breast cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) to be administered orally High grade serous/undifferentiated tubo-ovarian carcinoma with unknown BRCA status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally Known BRCA mutation positive ovarian cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Triple negative breast Cancer with unknown BRCA mutation status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally AZD2281, PARP inhibitor Olaparib tablets, oral | Drug: AZD2281<br>* PARP inhibitor Olaparib tablets, oral<br>* Other names: Olaparib;|
| Experimental: 2<br>Known BRCA mutation positive breast cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) to be administered orally AZD2281, PARP inhibitor Olaparib tablets, oral | Drug: AZD2281<br>* PARP inhibitor Olaparib tablets, oral<br>* Other names: Olaparib;|
| Experimental: 3<br>High grade serous/undifferentiated tubo-ovarian carcinoma with unknown BRCA status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally AZD2281, PARP inhibitor Olaparib tablets, oral | Drug: AZD2281<br>* PARP inhibitor Olaparib tablets, oral<br>* Other names: Olaparib;|
| Experimental: 4<br>Known BRCA mutation positive ovarian cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally AZD2281, PARP inhibitor Olaparib tablets, oral | Drug: AZD2281<br>* PARP inhibitor Olaparib tablets, oral<br>* Other names: Olaparib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) Guidelines | Percentage of participants with confirmed best RECIST response of complete response (CR) or partial response (PR). Patients with a best RECIST response of CR or PR had to have a confirmed response at least 28 days later. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Percentage of participants with confirmed best Response Evaluation Criteria In Solid Tumours (RECIST) response of complete response (CR), partial response (PR) orStable Disease (SD) | 16 Weeks | 
| Duration of Response | Duration of response is measured from the time the measurement criteria for CR or PR are met (whichever is first recorded) until the patient progresses (per RECIST criteria). If patient did not progress, they are censored at their last objective tumour assessment date. | RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010. | 
| Best Percentage Change From Baseline in Tumour Size | The best percentage change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions). | 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. | 
| CA-125 Levels (Ovarian Cancer Patients Only) | 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. | 24 weeks | 
| Progression Free Survival (PFS) | 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. | RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Ovarian cancer, BRCA, Triple negative, Poly(ADP ribose) polymerases, Known BRCA or Recurrent High Grade Serious/ Undifferentiated Tubo- Ovarian Carcinoma, Known BRCA or Triple Negative Breast Cancer