Feasibility Study) PB-PG-1014-35005 Trial of Intraoperative Cell Salvage vs. Transfusion in Ovarian Cancer A Feasibility Study Feasibility Study) PB-PG-1014-35005

Background Ovarian cancer is diagnosed in about 6000 women in England each year. Surgery for ovarian cancer is often extensive (cytoreductive surgery) and can result in substantial blood loss Allogeneic blood transfusion (ABT) is the mainstay for replenishment of blood lost in surgery Currently, donated blood is used to replace blood lost during surgery (usual care). Protocol (PB-PG-1014-35005) 17/09/2018

Background Strain on blood bank resources Deleterious effects of ABT, especially in oncological surgery Results of several studies have shown an increased incidence of postoperative infection Promotion of tumour growth (which is thought to occur secondary to immunosuppression) and other transfusion reactions Protocol (PB-PG-1014-35005) 17/09/2018

Background An alternative method of replacing blood is “intraoperative cell salvage” (IOCS) Research has shown that patients who have had their own blood back do better than patients who have donor blood in non-cancer related surgery Protocol (PB-PG-1014-35005) 17/09/2018

Three studies in gynaecological cancer surgery including a total of 90 patients who received reinfusion of IOCS blood during gynaecological cancer surgery with IOCS and 1312 patients had similar treatment without IOCS, including historical controls No study results showed adverse associations in patients who received salvaged blood, compared with historical controls across all the different clinical outcome measures previously mentioned. Protocol (PB-PG-1014-35005) 17/09/2018

However The use of IOCS in ovarian cancer surgery has been held back by concerns of reintroducing cancer cells although, reportedly, 80-100% of these cells have been removed Trial comparing outcomes following IOCS or donor blood in women undergoing surgery for ovarian cancer Need to assess the feasibility of conducting this study We shall test the methods to be used in the later trial and the way it will be organised Protocol (PB-PG-1014-35005) 17/09/2018

Aims and objectives Estimate the likely recruitment rate for the larger trial Provide estimates of likely completeness of outcome data Explore the practical logistics for theatres so that randomisation can be undertaken as late as possible Design data collection tools to collect resource use data from participants, medical records and hospital staff Confirm the resources required to run a larger trial The overall aim of this proposed feasibility study is to ensure that a larger fully powered trial can successfully be planned and delivered. It will test the processes for such a trial, ascertain its feasibility (particularly in relation to recruitment) and provide the necessary information for planning the larger trial. The aim of the future larger trial will be to assess the clinical and cost effectiveness of intra-operative cell salvage for women undergoing debulking surgery for ovarian cancer, compared with usual practice of transfusing donor blood as required. A range of clinical and economic outcomes will be captured (and their capture tested in this feasibility study) but the primary outcome is likely to be overall survival at five years. Protocol (PB-PG-1014-35005) 17/09/2018

Perceptions of the intervention, the information given, and the advantages and disadvantages of participation Surgeons will also be interviewed to understand their own perspectives on the trial. The qualitative element aims to explore the barriers and facilitators for women when deciding whether or not to participate Protocol (PB-PG-1014-35005) 17/09/2018

We are also including three sites to make sure we can test processes Identify factors influencing surgeons’ decisions about whether or not to participate in the study. We intend to mirror many aspects of the future larger trial to test the processes of running that trial. As recruitment is a key issue we are randomizing in this feasibility study to test women’s willingness to accept randomization We are also including three sites to make sure we can test processes Protocol (PB-PG-1014-35005) 17/09/2018

Trial Design Randomised, multi-centre, parallel group feasibility study in patients undergoing surgery for ovarian cancer Centres Truro, Plymouth, Gateshead Sixty participants will be randomised in a 1:1 ratio to intra- operative cell salvage (re-infusion of their own blood) or donor (allogeneic) blood transfusion during surgery Protocol (PB-PG-1014-35005) 17/09/2018

Inclusion Criteria Potential participants must satisfy the following criteria to be enrolled in the study: 18 years old or over Suspected or confirmed ovarian cancer (newly diagnosed) requiring debulking surgery, whether primary or interval (following chemotherapy) ECOG Performance Status 0-1 Willing to participate   Protocol (PB-PG-1014-35005) 17/09/2018

Exclusion Criteria Potential participants meeting any of the following criteria will be excluded from study participation: Diagnosis of concurrent malignancy Pregnant Allogeneic transfusion during the week prior to surgery Haemoglobinopathies (e.g. sickle cell, thalassaemia) Unwilling to accept donor blood (e.g. on religious grounds)   Protocol (PB-PG-1014-35005) 17/09/2018

Follow Up All participants will be followed up post-operatively as out- patients at six weeks and again three months later. In addition, participants recruited in the early part of the study will be followed up at subsequent three month intervals as time allows Protocol (PB-PG-1014-35005) 17/09/2018

Outcome Measures (proposed outcomes for main trial) Overall survival, Progression-free survival EQ-5D-5L EORTC QLQ-C30 (Version 3.0) Inadvertent visceral injury Return to theatre Surgical site infection Protocol (PB-PG-1014-35005) 17/09/2018

Outcome Measures (proposed outcomes for main trial) Thromboembolic complications (DVT, PE) Other post-operative complications Amount of allogeneic blood given (total and <24 hours post operation) Length of stay Protocol (PB-PG-1014-35005) 17/09/2018

Neoadjuvant chemotherapy Primary surgery Neoadjuvant chemotherapy 3 cycles of chemotherapy Informed consent Hospital admission  Baseline data collection  Randomisation  Operation IOCS (Intra Operative Cell Salvage) Standard Treatment (Allogeneic blood transfusion) 6 week follow-up  Follow-up data collection All participants 3 month follow-up  6 month follow-up  Protocol (PB-PG-1014-35005) 17/09/2018

Thank You Protocol (PB-PG-1014-35005) 17/09/2018