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

Phase 2

Completed

• Conditions: Ovarian Neoplasms
• Interventions: Drug: AZD2281; Drug: Liposomal Doxorubicin

• Registration Number: NCT00628251
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-02-26
• Study First Submitted QC: 2008-03-04
• Study First Posted: 2008-03-05
• Study Start: 2008-07-30
• Primary Completion: 2009-09-15
• Disposition First Submitted: 2013-07-22
• Disposition First Submitted QC: 2013-07-22
• Disposition First Posted: 2013-07-24
• Results First Submitted: 2015-01-14
• Results First Submitted QC: 2016-04-27
• Results First Posted: 2016-06-03
• Study Completion: 2018-09-19
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-12
• Last Update Posted: 2019-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 97

Inclusion Criteria

• Advanced ovarian cancer with positive BRCA1 or BRCA2 status
• Progressive or recurrent disease after platinum-based chemotherapy
• Measurable disease by RECIST

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	AZD2281	AZD2281 Oral 200 mg BID
2	Liposomal Doxorubicin	Liposomal Doxorubicin
3	AZD2281	AZD2281 Oral 400 mg BID

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	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)	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)

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	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.
Confirmed RECIST Response and/or CA-125 Response	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	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.
Overall Survival (OS)	At the time of the cut-off for the final analysis of overall survival (30 April 2010)	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
Overall Duration of Response	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	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.)
Disease Control Rate	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	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
Best Percentage Change in Tumour Size	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	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
Best Percentage Change From Baseline in CA-125 Levels	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	Best percentage change in cancer antigen 125 (CA-125) levels
Best Quality of Life (QoL) Response for Trial Outcome Index (TOI)	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	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.
Best QoL Response for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	Best HRQoL response using the total FACT-O endpoint. Improvement was defined as a change from baseline of greater than or equal to +9.
Best QoL Response for FACT-O Symptom Index (FOSI)	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)	Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sutton, United Kingdom