Unravelling Tumour Biology In Ovarian Cancer With Precision Imaging

High Grade Serous Ovarian Cancer Clinical Trial

— MR-O-MICS  

Official title:

Unravelling Tumour Biology In Ovarian Cancer With Precision Imaging

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06084195
• Other study ID #: PROICM 2023-02 MRO
• Status: Recruiting
• Phase: N/A
• Start date: December 19, 2023
• Est. completion date: October 2029

Study information

• Verified date: December 2023
• Source: Institut du Cancer de Montpellier - Val d'Aurelle
• Contact: MOUSSION Aurore
• Phone: 0467613102
• Email: aurore.moussion[@]icm.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to explore the integration of in vivo and ex vivo of MRI with histology and molecular assessments to advance non-invasive characterization of tumor heterogeneity in high-grade serous ovarian cance

Description:

After being informed about the study and potential risks, all patient giving wirtting informed consent.

During surgery, tissue and blood samples will be conserved for the study. In this study will be compared images obtained in vivo before surgical management, ex vivo images obtained on excised tissues during surgery, histological data obtained during surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: October 2029
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient aged >18

• Pathologically proven HGSOC at an advanced stage (FIGO IIIB or IIIC) which can benefit from surgery with or without prior neoadjuvant treatment

• Willingness and ability to comply with planned visits, treatment plan, laboratory tests and other study procedures,

• Patient who has given informed, written and express consent,

• Patient affiliated with a French health insurance scheme.

Exclusion Criteria:

• Early-stage disease (FIGO <IIIB) or presence of extraperitoneal metastases,

• Patient who will not have surgery

• Patient whose regular follow-up is impossible for psychological, family, social or geographical reasons,

• Patient under guardianship, curatorship or safeguarding of justice,

• Pregnant and/or nursing patient,

• Patient with a history of other cancers within 5 years/10 years prior to inclusion

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• High Grade Serous Ovarian Cancer
• Ovarian Neoplasms

Intervention

Biological:
• Blood sample and tissue sample
During the surgery : Tissus sample : primary tumor and metastasis blood sample : 3 EDTA tubes ex vivo MRI data

Locations

Country	Name	City	State
France	NOUGARET Stephanie	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
Institut du Cancer de Montpellier - Val d'Aurelle

Country where clinical trial is conducted

France, 

References & Publications (35)

Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. doi: 10.1056/NEJMoa052985. — View Citation

Avesani G, Arshad M, Lu H, Fotopoulou C, Cannone F, Melotti R, Aboagye E, Rockall A. Radiological assessment of Peritoneal Cancer Index on preoperative CT in ovarian cancer is related to surgical outcome and survival. Radiol Med. 2020 Aug;125(8):770-776. doi: 10.1007/s11547-020-01170-6. Epub 2020 Apr 1. — View Citation

Bankhead P, Loughrey MB, Fernandez JA, Dombrowski Y, McArt DG, Dunne PD, McQuaid S, Gray RT, Murray LJ, Coleman HG, James JA, Salto-Tellez M, Hamilton PW. QuPath: Open source software for digital pathology image analysis. Sci Rep. 2017 Dec 4;7(1):16878. doi: 10.1038/s41598-017-17204-5. — View Citation

Bashashati A, Ha G, Tone A, Ding J, Prentice LM, Roth A, Rosner J, Shumansky K, Kalloger S, Senz J, Yang W, McConechy M, Melnyk N, Anglesio M, Luk MT, Tse K, Zeng T, Moore R, Zhao Y, Marra MA, Gilks B, Yip S, Huntsman DG, McAlpine JN, Shah SP. Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling. J Pathol. 2013 Sep;231(1):21-34. doi: 10.1002/path.4230. — View Citation

Burrell RA, Swanton C. Tumour heterogeneity and the evolution of polyclonal drug resistance. Mol Oncol. 2014 Sep 12;8(6):1095-111. doi: 10.1016/j.molonc.2014.06.005. Epub 2014 Jul 10. — View Citation

Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166. Erratum In: Nature. 2012 Oct 11;490(7419):298. — View Citation

Cooke SL, Brenton JD. Evolution of platinum resistance in high-grade serous ovarian cancer. Lancet Oncol. 2011 Nov;12(12):1169-74. doi: 10.1016/S1470-2045(11)70123-1. — View Citation

Dai D, Liu L, Huang H, Chen S, Chen B, Cao J, Luo X, Wang F, Luo R, Liu J. Nomograms to Predict the Density of Tumor-Infiltrating Lymphocytes in Patients With High-Grade Serous Ovarian Cancer. Front Oncol. 2021 Feb 25;11:590414. doi: 10.3389/fonc.2021.590414. eCollection 2021. — View Citation

Engbersen MP, Van' T Sant I, Lok C, Lambregts DMJ, Sonke GS, Beets-Tan RGH, van Driel WJ, Lahaye MJ. MRI with diffusion-weighted imaging to predict feasibility of complete cytoreduction with the peritoneal cancer index (PCI) in advanced stage ovarian cancer patients. Eur J Radiol. 2019 May;114:146-151. doi: 10.1016/j.ejrad.2019.03.007. Epub 2019 Mar 15. — View Citation

Frey MK, Pothuri B. Homologous recombination deficiency (HRD) testing in ovarian cancer clinical practice: a review of the literature. Gynecol Oncol Res Pract. 2017 Feb 22;4:4. doi: 10.1186/s40661-017-0039-8. eCollection 2017. — View Citation

Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012 Jan 18;481(7381):306-13. doi: 10.1038/nature10762. — View Citation

Himoto Y, Veeraraghavan H, Zheng J, Zamarin D, Snyder A, Capanu M, Nougaret S, Vargas HA, Shitano F, Callahan M, Wang W, Sala E, Lakhman Y. Computed Tomography-Derived Radiomic Metrics Can Identify Responders to Immunotherapy in Ovarian Cancer. JCO Precis Oncol. 2019 Aug 15;3:PO.19.00038. doi: 10.1200/PO.19.00038. eCollection 2019. — View Citation

Hoogstraat M, de Pagter MS, Cirkel GA, van Roosmalen MJ, Harkins TT, Duran K, Kreeftmeijer J, Renkens I, Witteveen PO, Lee CC, Nijman IJ, Guy T, van 't Slot R, Jonges TN, Lolkema MP, Koudijs MJ, Zweemer RP, Voest EE, Cuppen E, Kloosterman WP. Genomic and transcriptomic plasticity in treatment-naive ovarian cancer. Genome Res. 2014 Feb;24(2):200-11. doi: 10.1101/gr.161026.113. Epub 2013 Nov 12. — View Citation

Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet. 2014 Oct 11;384(9951):1376-88. doi: 10.1016/S0140-6736(13)62146-7. Epub 2014 Apr 21. — View Citation

Jimenez-Sanchez A, Cybulska P, Mager KL, Koplev S, Cast O, Couturier DL, Memon D, Selenica P, Nikolovski I, Mazaheri Y, Bykov Y, Geyer FC, Macintyre G, Gavarro LM, Drews RM, Gill MB, Papanastasiou AD, Sosa RE, Soslow RA, Walther T, Shen R, Chi DS, Park KJ, Hollmann T, Reis-Filho JS, Markowetz F, Beltrao P, Vargas HA, Zamarin D, Brenton JD, Snyder A, Weigelt B, Sala E, Miller ML. Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy. Nat Genet. 2020 Jun;52(6):582-593. doi: 10.1038/s41588-020-0630-5. Epub 2020 Jun 1. — View Citation

Jimenez-Sanchez A, Memon D, Pourpe S, Veeraraghavan H, Li Y, Vargas HA, Gill MB, Park KJ, Zivanovic O, Konner J, Ricca J, Zamarin D, Walther T, Aghajanian C, Wolchok JD, Sala E, Merghoub T, Snyder A, Miller ML. Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient. Cell. 2017 Aug 24;170(5):927-938.e20. doi: 10.1016/j.cell.2017.07.025. — View Citation

Lambin P, Leijenaar RTH, Deist TM, Peerlings J, de Jong EEC, van Timmeren J, Sanduleanu S, Larue RTHM, Even AJG, Jochems A, van Wijk Y, Woodruff H, van Soest J, Lustberg T, Roelofs E, van Elmpt W, Dekker A, Mottaghy FM, Wildberger JE, Walsh S. Radiomics: the bridge between medical imaging and personalized medicine. Nat Rev Clin Oncol. 2017 Dec;14(12):749-762. doi: 10.1038/nrclinonc.2017.141. Epub 2017 Oct 4. — View Citation

Lee JY, Yoon JK, Kim B, Kim S, Kim MA, Lim H, Bang D, Song YS. Tumor evolution and intratumor heterogeneity of an epithelial ovarian cancer investigated using next-generation sequencing. BMC Cancer. 2015 Feb 26;15:85. doi: 10.1186/s12885-015-1077-4. — View Citation

Lou E, Vogel RI, Hoostal S, Klein M, Linden MA, Teoh D, Geller MA. Tumor-Stroma Proportion as a Predictive Biomarker of Resistance to Platinum-Based Chemotherapy in Patients With Ovarian Cancer. JAMA Oncol. 2019 Aug 1;5(8):1222-1224. doi: 10.1001/jamaoncol.2019.1943. — View Citation

McPherson A, Roth A, Laks E, Masud T, Bashashati A, Zhang AW, Ha G, Biele J, Yap D, Wan A, Prentice LM, Khattra J, Smith MA, Nielsen CB, Mullaly SC, Kalloger S, Karnezis A, Shumansky K, Siu C, Rosner J, Chan HL, Ho J, Melnyk N, Senz J, Yang W, Moore R, Mungall AJ, Marra MA, Bouchard-Cote A, Gilks CB, Huntsman DG, McAlpine JN, Aparicio S, Shah SP. Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer. Nat Genet. 2016 Jul;48(7):758-67. doi: 10.1038/ng.3573. Epub 2016 May 16. — View Citation

Michielsen K, Vergote I, Op de Beeck K, Amant F, Leunen K, Moerman P, Deroose C, Souverijns G, Dymarkowski S, De Keyzer F, Vandecaveye V. Whole-body MRI with diffusion-weighted sequence for staging of patients with suspected ovarian cancer: a clinical feasibility study in comparison to CT and FDG-PET/CT. Eur Radiol. 2014 Apr;24(4):889-901. doi: 10.1007/s00330-013-3083-8. Epub 2013 Dec 11. — View Citation

Ovarian Tumor Tissue Analysis (OTTA) Consortium; Goode EL, Block MS, Kalli KR, Vierkant RA, Chen W, Fogarty ZC, Gentry-Maharaj A, Toloczko A, Hein A, Bouligny AL, Jensen A, Osorio A, Hartkopf A, Ryan A, Chudecka-Glaz A, Magliocco AM, Hartmann A, Jung AY, Gao B, Hernandez BY, Fridley BL, McCauley BM, Kennedy CJ, Wang C, Karpinskyj C, de Sousa CB, Tiezzi DG, Wachter DL, Herpel E, Taran FA, Modugno F, Nelson G, Lubinski J, Menkiszak J, Alsop J, Lester J, Garcia-Donas J, Nation J, Hung J, Palacios J, Rothstein JH, Kelley JL, de Andrade JM, Robles-Diaz L, Intermaggio MP, Widschwendter M, Beckmann MW, Ruebner M, Jimenez-Linan M, Singh N, Oszurek O, Harnett PR, Rambau PF, Sinn P, Wagner P, Ghatage P, Sharma R, Edwards RP, Ness RB, Orsulic S, Brucker SY, Johnatty SE, Longacre TA, Ursula E, McGuire V, Sieh W, Natanzon Y, Li Z, Whittemore AS, Anna A, Staebler A, Karlan BY, Gilks B, Bowtell DD, Hogdall E, Candido dos Reis FJ, Steed H, Campbell IG, Gronwald J, Benitez J, Koziak JM, Chang-Claude J, Moysich KB, Kelemen LE, Cook LS, Goodman MT, Garcia MJ, Fasching PA, Kommoss S, Deen S, Kjaer SK, Menon U, Brenton JD, Pharoah PDP, Chenevix-Trench G, Huntsman DG, Winham SJ, Kobel M, Ramus SJ. Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer. JAMA Oncol. 2017 Dec 1;3(12):e173290. doi: 10.1001/jamaoncol.2017.3290. — View Citation

Pannu HK, Bristow RE, Montz FJ, Fishman EK. Multidetector CT of peritoneal carcinomatosis from ovarian cancer. Radiographics. 2003 May-Jun;23(3):687-701. doi: 10.1148/rg.233025105. — View Citation

Qayyum A, Coakley FV, Westphalen AC, Hricak H, Okuno WT, Powell B. Role of CT and MR imaging in predicting optimal cytoreduction of newly diagnosed primary epithelial ovarian cancer. Gynecol Oncol. 2005 Feb;96(2):301-6. doi: 10.1016/j.ygyno.2004.06.054. — View Citation

Schwarz RF, Ng CK, Cooke SL, Newman S, Temple J, Piskorz AM, Gale D, Sayal K, Murtaza M, Baldwin PJ, Rosenfeld N, Earl HM, Sala E, Jimenez-Linan M, Parkinson CA, Markowetz F, Brenton JD. Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis. PLoS Med. 2015 Feb 24;12(2):e1001789. doi: 10.1371/journal.pmed.1001789. eCollection 2015 Feb. — View Citation

Simidjievski N, Bodnar C, Tariq I, Scherer P, Andres Terre H, Shams Z, Jamnik M, Lio P. Variational Autoencoders for Cancer Data Integration: Design Principles and Computational Practice. Front Genet. 2019 Dec 11;10:1205. doi: 10.3389/fgene.2019.01205. eCollection 2019. — View Citation

Tardieu M, Lakhman Y, Khellaf L, Cardoso M, Sgarbura O, Colombo PE, Crispin-Ortuzar M, Sala E, Goze-Bac C, Nougaret S. Assessing Histology Structures by Ex Vivo MR Microscopy and Exploring the Link Between MRM-Derived Radiomic Features and Histopathology in Ovarian Cancer. Front Oncol. 2022 Jan 19;11:771848. doi: 10.3389/fonc.2021.771848. eCollection 2021. — View Citation

Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A, Siegel RL. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018 Jul;68(4):284-296. doi: 10.3322/caac.21456. Epub 2018 May 29. — View Citation

van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, de Hingh IHJT, van der Velden J, Arts HJ, Massuger LFAG, Aalbers AGJ, Verwaal VJ, Kieffer JM, Van de Vijver KK, van Tinteren H, Aaronson NK, Sonke GS. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan 18;378(3):230-240. doi: 10.1056/NEJMoa1708618. — View Citation

van Griethuysen JJM, Fedorov A, Parmar C, Hosny A, Aucoin N, Narayan V, Beets-Tan RGH, Fillion-Robin JC, Pieper S, Aerts HJWL. Computational Radiomics System to Decode the Radiographic Phenotype. Cancer Res. 2017 Nov 1;77(21):e104-e107. doi: 10.1158/0008-5472.CAN-17-0339. — View Citation

Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; European Organization for Research and Treatment of Cancer-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. doi: 10.1056/NEJMoa0908806. — View Citation

Weigelt B, Vargas HA, Selenica P, Geyer FC, Mazaheri Y, Blecua P, Conlon N, Hoang LN, Jungbluth AA, Snyder A, Ng CKY, Papanastasiou AD, Sosa RE, Soslow RA, Chi DS, Gardner GJ, Shen R, Reis-Filho JS, Sala E. Radiogenomics Analysis of Intratumor Heterogeneity in a Patient With High-Grade Serous Ovarian Cancer. JCO Precis Oncol. 2019 Jun 6;3:PO.18.00410. doi: 10.1200/PO.18.00410. eCollection 2019. No abstract available. — View Citation

Yildirim N, Akman L, Acar K, Demir S, Ozkan S, Alan N, Zekioglu O, Terek MC, Ozdemir N, Ozsaran A. Do tumor-infiltrating lymphocytes really indicate favorable prognosis in epithelial ovarian cancer? Eur J Obstet Gynecol Reprod Biol. 2017 Aug;215:55-61. doi: 10.1016/j.ejogrb.2017.06.005. Epub 2017 Jun 4. — View Citation

Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, Funnell T, Little N, de Souza CPE, Laan S, LeDoux S, Cochrane DR, Lim JLP, Yang W, Roth A, Smith MA, Ho J, Tse K, Zeng T, Shlafman I, Mayo MR, Moore R, Failmezger H, Heindl A, Wang YK, Bashashati A, Grewal DS, Brown SD, Lai D, Wan ANC, Nielsen CB, Huebner C, Tessier-Cloutier B, Anglesio MS, Bouchard-Cote A, Yuan Y, Wasserman WW, Gilks CB, Karnezis AN, Aparicio S, McAlpine JN, Huntsman DG, Holt RA, Nelson BH, Shah SP. Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer. Cell. 2018 Jun 14;173(7):1755-1769.e22. doi: 10.1016/j.cell.2018.03.073. Epub 2018 May 10. — View Citation

Zwanenburg A, Vallieres M, Abdalah MA, Aerts HJWL, Andrearczyk V, Apte A, Ashrafinia S, Bakas S, Beukinga RJ, Boellaard R, Bogowicz M, Boldrini L, Buvat I, Cook GJR, Davatzikos C, Depeursinge A, Desseroit MC, Dinapoli N, Dinh CV, Echegaray S, El Naqa I, Fedorov AY, Gatta R, Gillies RJ, Goh V, Gotz M, Guckenberger M, Ha SM, Hatt M, Isensee F, Lambin P, Leger S, Leijenaar RTH, Lenkowicz J, Lippert F, Losnegard A, Maier-Hein KH, Morin O, Muller H, Napel S, Nioche C, Orlhac F, Pati S, Pfaehler EAG, Rahmim A, Rao AUK, Scherer J, Siddique MM, Sijtsema NM, Socarras Fernandez J, Spezi E, Steenbakkers RJHM, Tanadini-Lang S, Thorwarth D, Troost EGC, Upadhaya T, Valentini V, van Dijk LV, van Griethuysen J, van Velden FHP, Whybra P, Richter C, Lock S. The Image Biomarker Standardization Initiative: Standardized Quantitative Radiomics for High-Throughput Image-based Phenotyping. Radiology. 2020 May;295(2):328-338. doi: 10.1148/radiol.2020191145. Epub 2020 Mar 10. — View Citation

* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the integration of in vivo and ex vivo of MRI with histology and molecular assessments to advance non-invasive characterization of tumor heterogeneity in high-grade serous ovarian cancer.	The diagnostic performance of the radiomic and multiomic algorithm for the characterization of heterogeneity in the CSOHG.	one shoot at the surgery
Secondary	the imaging phenotype of tumor heterogeneity with a multi-scale radiomic approach by obtaining the image mirror tumor at the in vivo scale	Correlation between radiomic maps and pathogenic maps of heterogeneity,	one shoot at the surgery
Secondary	tumor heterogeneity based on phenotypic imaging supported by AI reflects and can predict sub-histologyunderlying by tumor stroma proportion and tumor density infiltrating lymphocytes and genomics through HRD	Correlation between radiomic algorithms and i/underlying histology and ii/ genomics	one shoot at the surgery
Secondary	the heterogeneity of the tumor biology of CSOHG through non-invasive habitat imaging combined with an integrated Multi-O-Mics approach.	Correlation between radiomic maps and tumor biology (CYTOF, proteomics and transcriptomics),	one shoot at the surgery
Secondary	To Correlate MRI results with hematological molecular biology results.	Correlation between radiomic algorithms for tumor detection and cDNA determination.	one shoot at the surgery