Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Breast Cancer

Study Overview
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Brief Summary
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The purpose of the study is to see if the drug KU 0059436 (olaparib) is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists

Official Title
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A Phase II Open-label, Non-comparative, International, Multicentre Study to Assess the Efficacy and Safety of KU 0059436 (Olaparib) Given Orally Twice Daily in Patients With Advanced BRCA1 or BRCA2 Associated Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: KU-0059436 (AZD2281) (PARP inhibitor)
* Drug: KU-0059436 (AZD2281) (PARP inhibitor)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced breast cancer with positive BRCA1 or BRCA2 status Failed at least one prior chemotherapy In investigators opinion, no curative standard therapy exists Measurable disease Exclusion Criteria: Brain metastases Less than 28 days since last treatment used to treat the disease Considered a poor medical risk due to a serious uncontrolled disorder

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

Sexes Eligible for Study
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Female

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KU-0059436 (AZD2281) 100 mg BID<br> | Drug: KU-0059436 (AZD2281) (PARP inhibitor)<br>* oral<br>* Other names: Olaparib;|
| Experimental: KU-0059436 (AZD2281) 400 mg BID<br> | Drug: KU-0059436 (AZD2281) (PARP inhibitor)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Objective Tumour Response (According to RECIST Criteria) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy. Up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response to Olaparib |  | Time from response (CR or PR) to progression per RECIST criteria | 
| The Clinical Benefit Rate (CBR) | The Clinical Benefit Rate (CBR) is defined as the percentage of patients with a RECIST tumour response of confirmed CR, PR or stable disease (SD) for ≥8 weeks +/- 1 week visit window. | End of study | 
| Best Percent Change in Tumour Size | The tumour size is defined as the sum of the longest diameters as measured among all target lesions. | End of study | 
| Progression-Free Survival (PFS) | PFS is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression. Those patients who were withdrawn from the study without disease progression were regarded as censored at their last evaluable RECIST assessment. Where patients had not progressed at the termination of the study, they were also regarded as censored at their last evaluable RECIST assessment. | End of study | 
| Change From Baseline in ECOG Performance Status: Improvement Rate | The change in ECOG performance status was defined as improved (meaning the ECOG score is less than the baseline value), no change (ECOG is same as at baseline), worsened (ECOG score is greater than the baseline value) or missing (the ECOG score is missing or was not recorded at baseline). If no measurement was recorded at Cycle 1 Day 1, the change was calculated in relation to the last recorded ECOG value prior to Day 1. | At cycle 7 day 1 (ie, after completing 6 cycles of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced breast cancer, Poly(ADP ribose) polymerases, AZD2281,KU-0059436 (olaparib), BRCA1 protein, BRCA2 protein