PMID- 34783204 OWN - NLM STAT- MEDLINE DCOM- 20220128 LR - 20231105 IS - 2005-0399 (Electronic) IS - 2005-0380 (Print) IS - 2005-0380 (Linking) VI - 33 IP - 1 DP - 2022 Jan TI - Clinical Trial Protocol for HyNOVA: Hyperthermic and Normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III epithelial OVArian, fallopian tube and primary peritoneal cancer (ANZGOG1901/2020). PG - e1 LID - 10.3802/jgo.2022.33.e1 [doi] LID - e1 AB - BACKGROUND: Ovarian cancer is the most lethal gynecological cancer, causing over 200,000 deaths worldwide in 2020. Initial standard treatment for primary ovarian cancer is optimal cytoreductive surgery (CRS) preceded and/or followed by intravenous platinum-based chemotherapy. However, most women develop recurrence within the peritoneal cavity and die of disease. Results of the OVIHIPEC 1 trial (2018) showed improved survival of 34% when hyperthermic intraperitoneal chemotherapy (HIPEC) was given immediately following interval-CRS in women with stage III disease. However, it is unknown if the effect of HIPEC is due to hyperthermia, one extra cycle of intraperitoneal (IP) chemotherapy, or other factors. There is also concern that hyperthermia might be associated with an increase in adverse events (AEs) due to a heightened systemic inflammatory response. HyNOVA is a seamless, multi-stage randomized study that attempts to answer these questions by comparing HIPEC to normothermic intraperitoneal chemotherapy (NIPEC), focusing on safety (stage 1), then assessing activity (stage 2) and effectiveness (stage 3). In this initial study, we hypothesize that NIPEC will result in a lower rate of severe AEs compared to HIPEC. METHODS: This initial stage of HyNOVA is a phase II study of 80 women with International Federation of Gynaecology and Obstetrics stage III epithelial ovarian cancer, with at least stable disease following 3-4 cycles of neoadjuvant chemotherapy, achieving interval-CRS to <2.5 mm residual disease. Participants are randomized 1:1 to receive IP cisplatin 100 mg/m(2) for 90 minutes either as HIPEC, heated to 42 degrees C (41.5 degrees C-42.5 degrees C), or NIPEC, at 37 degrees C (36.5 degrees C-37.5 degrees C). The primary outcome is the proportion of AEs >/= grade 3 occurring within 90 days. Secondary outcomes are AE of interest, surgical morbidity, patient reported outcomes, resource allocation, feasibility, progression-free survival and overall survival. AEs are measured using both CTCAE v5.0 and Clavien-Dindo classification, particularly infection, pain, bowel dysfunction, and anemia. Tertiary outcomes are potential predictive biomarkers measured before and after HIPEC/NIPEC including circulating cell-free tumor DNA, tissue factors, and systemic inflammatory markers. There are 4 participating Australian sites with experience in CRS and HIPEC for peritoneal malignancy. HyNOVA is funded by an MRFF grant (APP1199155). TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12621000269831. CI - Copyright (c) 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology. FAU - Farrell, Rhonda AU - Farrell R AUID- ORCID: 0000-0001-7036-8968 AD - Chris O'Brien Lifehouse, Sydney, Australia. AD - University of Sydney, Sydney, Australia. rhondafarrell@mac.com. FAU - Burling, Michael AU - Burling M AUID- ORCID: 0000-0002-7112-3329 AD - NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. AD - Department of Gynecological Oncology, Westmead Hospital, Sydney, Australia. FAU - Lee, Yeh Chen AU - Lee YC AUID- ORCID: 0000-0003-2009-8263 AD - Chris O'Brien Lifehouse, Sydney, Australia. AD - NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. FAU - Pather, Selvan AU - Pather S AUID- ORCID: 0000-0002-1130-4275 AD - Chris O'Brien Lifehouse, Sydney, Australia. AD - University of Sydney, Sydney, Australia. FAU - Robledo, Kristy AU - Robledo K AUID- ORCID: 0000-0003-0213-7652 AD - NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. FAU - Mercieca-Bebber, Rebecca AU - Mercieca-Bebber R AUID- ORCID: 0000-0003-3708-9099 AD - NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. FAU - Stockler, Martin AU - Stockler M AUID- ORCID: 0000-0003-3793-8724 AD - Chris O'Brien Lifehouse, Sydney, Australia. AD - NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. CN - HyNOVA Protocol Steering Committee LA - eng SI - ANZCTR/ACTRN12621000269831 PT - Clinical Trial Protocol PT - Journal Article DEP - 20211018 PL - Korea (South) TA - J Gynecol Oncol JT - Journal of gynecologic oncology JID - 101483150 SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Australia MH - Clinical Trials, Phase II as Topic MH - Combined Modality Therapy MH - Cytoreduction Surgical Procedures MH - Fallopian Tubes MH - Female MH - Humans MH - *Hyperthermia, Induced MH - *Ovarian Neoplasms/drug therapy MH - *Peritoneal Neoplasms/drug therapy MH - Randomized Controlled Trials as Topic PMC - PMC8728663 OTO - NOTNLM OT - Chemotherapy OT - Hyperthermia OT - Ovarian Cancer OT - Patient Reported Outcomes COIS- No potential conflict of interest relevant to this article was reported. EDAT- 2021/11/17 06:00 MHDA- 2022/01/29 06:00 PMCR- 2022/01/01 CRDT- 2021/11/16 07:08 PHST- 2021/06/17 00:00 [received] PHST- 2021/08/17 00:00 [revised] PHST- 2021/10/05 00:00 [accepted] PHST- 2021/11/17 06:00 [pubmed] PHST- 2022/01/29 06:00 [medline] PHST- 2021/11/16 07:08 [entrez] PHST- 2022/01/01 00:00 [pmc-release] AID - 33.e1 [pii] AID - 10.3802/jgo.2022.33.e1 [doi] PST - ppublish SO - J Gynecol Oncol. 2022 Jan;33(1):e1. doi: 10.3802/jgo.2022.33.e1. Epub 2021 Oct 18.