Background: The role and the duration of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (AOC) are still debated. A phase III randomized trial showed that 3 courses of NACT followed by surgery were not inferior to primary debulking surgery followed by chemotherapy (CHT) for patients (pts) with AOC. Moreover, the absence of residual tumor after surgery was found to be the single most important independent prognostic factor. In our preliminary experience pts with bulky stage IIIC or IV AOC were treated with 6 courses of NACT followed by surgery and we observed a complete cytoreduction rate up to 63% ; the survival data did not suggest a detrimental effect of such strategy. Considering the lack of evidence regarding the best standard of care for pts with AOC, a randomized study of 3 vs 6 courses of NACT was designed to verify if 3 more courses of NACT are associated to an increase of complete cytoreductive surgery rate (CCSR) (primary end-point). Methods: this is a multicenter randomized, phase II study of 3 vs 6 courses of NACT in AOC. The main eligibility criteria are ECOG PS ≥ 2, histologically confirmed FIGO stage IIIC-IV epithelial ovarian cancer, unsuitable for complete primary cytoreductive surgery (inoperability confirmed by open laparoscopy or laparotomy). Pts will receive 3 or 6 courses of i.v. carboplatin AUC 5 and paclitaxel 175 mg/m² every 3 weeks, followed by surgery.Tumor tissue will be collected for analyses of prognostic and predictive biomarkers, including ESR1 mRNA, HER2 and HER3 expression, BRCA1, BRCA2 and PI3KCA mutations. By hypothesizing a CCSR of 43% in Arm A (3 courses) and 63% in Arm B (6 courses), with a two-sided alpha error of 0.05 and a power of 0.80, 214 pts (107 in each arm) are to be enrolled in 2 years. An interim analysis has been scheduled after the first 120 pts in order to end the enrollment in the phase II and to start a phase III (with survival as primary endpoint) in case of the endpoint for efficacy (CCSR) will be reached at that time. The sample size of the interim analysis was calculated by considering the same alpha error (0.05) but a lower power value (0.50) than those of the global sample size calculation. The first patient was enrolled in January 2014. Clinical trial information: 2013-002520-17.