TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO-OVAR OP7).

Background: Primary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was subsequently reported by two randomized phase III trials (EORTC-GCG, CHORUS), which were criticized owing to important limitations, especially regarding the rate of complete resection.
Primary Objective: To clarify the optimal timing of surgical therapy in advanced ovarian cancer.
Study Hypothesis: Primary cytoreductive surgery is superior to interval cytoreductive surgery following neoadjuvant chemotherapy for overall survival in patients with advanced ovarian cancer.
Trial Design: TRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreductive surgery in patients with FIGO stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma. To guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (eg, ≥50% complete resection rate in upfront surgery for FIGO IIIB-IVB patients, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST quality committee delegates. Patients in the primary cytoreductive surgery arm undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas patients in the interval cytoreductive surgery arm undergo 3 cycles of neoadjuvant chemotherapy after histologic confirmation of the disease, followed by interval cytoreductive surgery and subsequently, 3 cycles of platinum-based chemotherapy. The intention of surgery for both groups is complete tumor resection according to guideline recommendations.
Major Inclusion/exclusion Criteria: Major inclusion criteria are suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma FIGO stage IIIB-IVB (IV only if resectable metastasis). Major exclusion criteria are non-epithelial ovarian malignancies and borderline tumors; prior chemotherapy for ovarian cancer; or abdominal/pelvic radiotherapy.
Primary Endpoint: Overall survival.
Sample Size: 772 patients.
Estimated Dates for Completing Accrual and Presenting Results: Accrual completion approximately mid-2019, results are expected after 5 years' follow-up in 2024.
Trial Registration: NCT02828618.
Competing Interests: Competing interests: AdB reports personal fees from Roche, Astra Zeneca, BIOCAD, Genmab, Clovis, Tesaro, PharmaMar, Pfizer, outside the submitted work. PH reports grants and personal fees from Astra Zeneca, Roche, Tesaro, Public funding (ASCO, DKH, DFG), personal fees from Sotio, Stryker, Zai Lab, MSD, Clovis, Immunogen, grants from GSK, Boehringer Ingelheim, Medac, Genmab, outside the submitted work. CF reports personal fees from Roche, Tesaro, Astra Zeneca, Olympus, Ethicon, outside the submitted work. A Reinthaller reports research grants from Roche; honoraria as a speaker and for advisory boards from Amgen, Astra Zeneca, MSD, PharmaMar, Roche, Tesaro, Vifor Pharma; travel expenses from Amgen, Astra Zeneca, PharmaMar, Roche, Tesaro. FH reports personal fees from Astra Zeneca, Roche, PharmaMar, Tesaro, Clovis, outside the submitted work. DSC reports personal fees from Bovie Medical Co., Verthermia Inc. (now Apyx Medical Corp.), C Surgeries, Biom ‘Up, other from Intuitive Surgical, Inc., TransEnterix, Inc., outside the submitted work. SM reports grants and personal fees from AstraZeneca, Medac, MSD, PharmaMar, Roche, Tesaro, Teva, personal fees from Clovis, Novartis, Olympus Europa, Sensor Kinesis, outside the submitted work.
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