384TiPEffectiveness of olaparib plus trastuzumab in HER2[+], BRCA –mutated (BRCAm) or homologous recombination deficient (HRD) advanced breast cancer (ABC) patients (pts). The OPHELIA study

This study will evaluate the efficacy and safety of olaparib plus trastuzumab in HER2[+] gBRCAm or wild–type gBRCA/HRD ABC pts.Trial designThis is a multicenter, single –arm, two–cohort, Simon’s two–stage, phase II trial. The cohort A will recruit N = 20 gBRCAm ABC pts. The cohort B will recruit N = 13 wild–type gBRCA/HRD ABC pts based on HRDetect assay. Pts will receive olaparib (300mg p.o. b.i.d. during 21–day cycles) in combination with trast uzumab (IV/SC at standard dose) until progression or unacceptable toxicity. Main selection criteria: (1) Pre– and post–menopausal women with HER2[+] ABC; (2) ≤3 prior regimens of chemotherapy and/or trastuzumab–lapatinib in advanced setting, and at least 1 regimen of chemotherapy including t rastuzumab; (3) Pts treated with carboplatin or platinum compounds in the last 12 months are not eligible; (4) Evaluable or measurable disease. Co–Primary objectives: Overall response rate (ORR) and PFS of olaparib plus trastuzumab in the cohort A. In the cohort A (N = 20), we plan a Simon’s two–stage design (7 pts in the 1st stage and 13 pts in the 2nd stage in case of any responder in 1st stage). Final ORR will be promising with ≥4 responders among 18 evaluable pts (H0: ORR≤5%; HA: ORR≥30%). PFS estimation will be based a one–arm log–rank test (H0: PFS≤3–months; HA: PFS≥6–months). These give us an 80% power at 0.025 one–sided alpha level. In the cohort B (N = 13) ORR will be promisi...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research