Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer

Study Overview
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Brief Summary
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The purpose of the study is to compare the efficacy and safety of 2 doses of drug AZD2281 against liposomal doxorubicin to see which is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and who have failed previous platinum therapy.

Official Title
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A Phase II, Open-Label, Randomised, Comparative, International Multicentre Study to Assess the Safety and Efficacy of Different Doses of AZD2281 Given Orally Twice Daily Versus Intravenous Liposomal Doxorubicin Given Monthly in Patients With Advanced BRCA1- or BRCA2-Associated Ovarian Cancer Who Have Failed Previous Platinum-based Chemotherapy

Conditions
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Ovarian Neoplasms

Intervention / Treatment
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* Drug: AZD2281
* Drug: Liposomal Doxorubicin
* Drug: AZD2281


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced ovarian cancer with positive BRCA1 or BRCA2 status Progressive or recurrent disease after platinum-based chemotherapy Measurable disease by RECIST Exclusion Criteria: Previous anthracycline treatment 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD2281 Oral 200 mg BID | Drug: AZD2281<br>* 200mg oral twice daily<br>|
| Active Comparator: 2<br>Liposomal Doxorubicin | Drug: Liposomal Doxorubicin<br>* 50mg/m2 Monthly Intravenous<br>* Other names: Doxil®;|
| Experimental: 3<br>AZD2281 Oral 400 mg BID | Drug: AZD2281<br>* 400mg Oral twice daily<br>* Other names: Olaparib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS was defined as the time to progression from the date of randomisation until the date of radiological assessment of progression per RECIST criteria or death (by any cause in the absence of progression) | Tumour assessment was to be assessed at screening, every 8 weeks during the study and at the withdrawal visit, up to 56 weeks. (Data cut-off for primary analysis of PFS: 15 September 2009) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR was defined according to RECIST. Complete response (CR) or partial response - (PR)- 30% decrease Patients with a best RECIST response of CR or PR had to have a confirmed response at least 28 days later. | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 
| Disease Control Rate | The number of patients with confirmed CR (disappearance of all target lesions) or PR (30% decrease in the sum of the longest diameter of target lesions ) or SD ( small changes ) >4 months, divided by the number of randomised patients | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 
| Overall Duration of Response | The duration of response was defined as time (months) from initial assessment of PR/CR until earliest date of objective progression or death. (Values may be underestimated as some patients had not progressed at final analysis so true duration is likely to be greater than that in database.) | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 
| Best Percentage Change in Tumour Size | The percentage change (reduction) from baseline in the sum of the lengths of the longest diameter (LD) of the RECIST target lesions were objectively documented, regardless of whether the patient was still taking study medication | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 
| Best Percentage Change From Baseline in CA-125 Levels | Best percentage change in cancer antigen 125 (CA-125) levels | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 
| Confirmed RECIST Response and/or CA-125 Response | The percentage of patients reporting a RECIST confirmed response and/or a CA-125 response (in the absence of progression). A CA-125 response was defined as a confirmed greater or equal to 50% reduction in CA-125. | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 
| Overall Survival (OS) | OS was defined as time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date they were known to be alive. Median OS was not calculable for olaparib groups due to an insufficient number of deaths so the percentage of participants who died are shown along with 95% confidence intervals | At the time of the cut-off for the final analysis of overall survival (30 April 2010) | 
| Best Quality of Life (QoL) Response for Trial Outcome Index (TOI) | Best HRQoL response using the TOI endpoint. Improvement was defined as a change from baseline of greater than or equal to +7. The TOI score ranges from 0-100. | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 
| Best QoL Response for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O) | Best HRQoL response using the total FACT-O endpoint. Improvement was defined as a change from baseline of greater than or equal to +9. | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 
| Best QoL Response for FACT-O Symptom Index (FOSI) | Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3. | At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced ovarian cancer, BRCA1 protein, BRCA2 protein, Poly(ADP ribose) polymerases