Summary
This open label, randomised, controlled, multi-centre phase III study will assess the efficacy and safety of single agent olaparib vs standard of care based on physician's choice of capecitabine, vinorelbine or eribulin in metastatic breast cancer patients with gBRCA 1/2 mutations.
Objectives
Primary Outcome Measures:
Secondary Outcome Measures:
-
Overall Survival [ Time Frame: Assessed at time of PFS analysis and when approx 60% patients have died by any cause (on average 15 months after randomisation). Survival assessed every 8 weeks following objective disease progression. Data collection will last up to approx 7 years. ] [ Designated as safety issue: No ]
Efficacy of single agent olaparib vs physician's choice chemotherapy (capecitabine, vinorelbine or eribulin) by assessment of overall survival (OS). This assessment is performed until the time of the final OS analysis (when approximately 60% patients have died).
-
Time from randomisation to second progression or death (PFS2). [ Time Frame: Assessed at time of PFS analysis and at final OS analysis. After first objective disease progression by RECIST, patients will then be assessed every 8 weeks for second progression. Data collection will last up to approx 7 years. ] [ Designated as safety issue: No ]
Efficacy of single agent olaparib vs physician's choice chemotherapy (capecitabine, vinorelbine or eribulin) by assessment of time to second progression, defined as objective radiological or symptomatic progression, or death (PFS2). This assessment is performed until the time of the final OS analysis (when approximately 60% patients have died).
-
Objective Response Rate by BICR using RECIST 1.1 [ Time Frame: Assessed at time of PFS analysis. RECIST assessments are performed at baseline, every 6 weeks for the first 6 months, then every 12 weeks until objective disease progression. Data collection will last up to approx 7 years. ] [ Designated as safety issue: No ]
Efficacy of single agent olaparib vs physician's choice chemotherapy (capecitabine, vinorelbine or eribulin) by assessment of objective response rate (ORR) using BICR data assessed by RECIST 1.1.
-
Adjusted mean change from baseline in global QoL score from the EORTC-QLQ-C30 questionnaire. [ Time Frame: EORTC QLQ-C30 questionnaires to be completed at baseline and every 6 weeks until disease progression. Study data collection is expected to last up to approximately 7 years. ] [ Designated as safety issue: No ]
Assessment of the effect of olaparib on the Health-related Quality of Life (HRQoL) as measured by EORTC QLQ-C30 global QoL scale.
-
Safety and tolerability of olaparib by assessment of adverse events. [ Time Frame: Adverse events collected from informed consent until post treatment 30-day follow-up period. Study data collection is expected to last up to approximately 7 years. ] [ Designated as safety issue: Yes ]
Assessment of adverse events (AEs), graded by CTCAE (v4.0).
-
Safety and tolerability of olaparib by assessment of physical examination. [ Time Frame: Physical examinations carried out at baseline and until study treatment discontinued and at the post treatment 30-day follow-up visit. Study data collection is expected to last up to approximately 7 years. ] [ Designated as safety issue: Yes ]
Assessment of physical examination.
-
Safety and tolerability of olaparib by assessment of vital signs. [ Time Frame: Vital signs assessments collected at baseline and until study treatment discontinued and at the post treatment 30-day follow-up visit. Study data collection is expected to last up to approximately 7 years. ] [ Designated as safety issue: Yes ]
Assessment of vital signs including blood pressure (BP), pulse and electrocardiogram (ECG).
-
Safety and tolerability of olaparib by assessment of laboratory parameters. [ Time Frame: Laboratory parameter assessments collected at baseline and until study treatment discontinued and at the post treatment 30-day follow-up visit. Study data collection is expected to last up to approximately 7 years. ] [ Designated as safety issue: Yes ]
Assessment of laboratory parameters including clinical chemistry and haematology.