TRUST: Trial of radical upfront surgical therapy in advanced ovarian cancer (ENGOT ov33 / AGO‐OVAR OP7).

Abstract

TPS5602 Background: Primary cytoreductive surgery (PDS) followed by chemotherapy has been considered as standard management for advanced ovarian cancer patients (pts) over decades. An alternative approach of interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT) was subsequently reported by two randomized phase III trials (EORTC‐GCG, CHORUS). Owing to important limitations of these studies, especially regarding surgical quality, optimal timing of surgical therapy in advanced ovarian cancer is still unclear. Methods: TRUST is an international open, randomized, controlled multicenter trial investigating overall survival (OS; primary endpoint) after PDS vs NACT and subsequent IDS in pts with FIGO stage IIIB‐IVB ovarian, tubal, and peritoneal carcinoma. Secondary objectives are safety of complete tumor resection, progression‐free survival and quality of life (QoL) as well as surgical morbidity. In order to guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (e.g. ≥50% complete resection rate in upfront surgery for FIGO IIIB-IV pts, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST Quality committee delegates. A 1:1 randomization to PDS or NACT followed by IDS stratified by center and age‐ECOG combination (ECOG 0 and age ≤65 years vs ECOG > 0 or age > 65 years) is performed. Pts in the PDS arm will undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas pts in the IDS arm will be treated with 3 cycles of NACT after histologic confirmation of the disease, followed by IDS and subsequently 3 cycles of platinum-based chemotherapy. Intention of surgery for both groups will be complete tumor resection as per guideline recommendations. Health related QoL will be assessed using the EORTC QLQ‐C30, QLQ‐OV28, and EQ‐5D‐3L questionnaires. For sample size planning, we considered a prolongation of median OS from 45 months in the IDS arm to 60 months in the PDS arm (HR 0.75) as clinically relevant. 380 events are needed to obtain a power of 80% in two‐sided log-rank test with significance level of 0.05. The primary analysis will be done in the ITT‐population of 686 randomized pts. By Feb 3 2017, 46 pts were randomized. Clinical trial information: NCT02828618.