MITO 31 A phase II trial of Olaparib in patients with recurrent ovarian cancer wild type for germline and somatic BRCA mutations: a MITO translational study S. Pignata

Background PARP Inibitori sono attivi anche in pazienti senza mutazione Olaparib in indicazione solo per pazienti mutate germline e somatiche 14 % delle pazienti trattate in studio 19 in trattamento dopo 5 anni (mutate e non) 20-30 % delle pazienti trattate con Niraparib, HRD negative restano in trattamento per oltre 18 mesi

Ipotesi di studio Studio di fase 2 con olaparib 300 mg bid (nuova fomulazione) in 200 pazienti BRCA germline wt e senza mutazione BRCA somatico (piattaforma disponibile) Studio traslazionale con raccolta di paraffinato (Napoli) e sangue (Aviano) per identificare le long responders

Disegno statistico The study has an exploratory nature therefore no a-priori hypothesis has been made on the primary endpoint (PFS). With 164 patients the trial will be able to find a potential biomarker (including a profile of biomarkers), that we estimate being present in 15 % of the cases (Progression-free for > 12 months, long-responders), associated with a HR of PFS=0.5, with alpha (one-tailed) of 0.1 and power of 90 %, with the final analysis performed after 140 events. (Schoenfeld, Biometrics 1983; 39, 499-503) Considering the possibility that a proportion of the samples collected would not be eligible for the molecular analysis, we plan to enroll 200 patients in this trial.

Disegno statistico new The study has an exploratory nature therefore no a-priori hypothesis has been made on the primary endpoint (PFS). Sample size was estimated according to suggestions of Schoenfeld 1. With 90% power, two-tailed alpha=0.1 and 140 events, the study is able to detect, a 0.50 Hazard Ratio (HR) of progression/death events associated with a biomarker expressed in 15% of the patients. For prevalence rates higher than 15%, the statistical power is actually higher. Therefore, a sample of 200 patients enrolled in 24 months should be sufficient. Such sample size estimation deliberately does not take into account the issue of multiplicity that will not be addressed given the exploratory nature of the study. Considering the possibility that a proportion of the samples collected would not be eligible for the molecular analysis, we plan to enroll 200 patients in this trial. 1. Schoenfeld, Biometrics 1983; 39, 499-503