Clinical trial NCT04555473: Translational Analysis In Longitudinal Series of Ovarian Cancer ORganoids
Official title: Translational Analysis In Longitudinal Series of Ovarian Cancer ORganoids
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Organoids
Epithelial Ovarian Cancer
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2020-09-18
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible population included women with preoperative clinical, serological and radiologic suspicion of International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV ovarian, fallopian tube, or primary peritoneal cancer, and histological confirmation of diagnosis for HGSOC. Stage IV patients were included only in case of positive pleural effusion, or any resectable disease. All women were required to sign written informed consent to enter the study.

Brief summary: This is a longitudinal observational phase II, single center, single arm study on the reliability of high grade serous ovarian carcinoma organoids obtained from primary debulking surgery (PDS)+adjuvant chemotherapy and neoadjuvant chemotherapy + interval debulking surgery (NACT+IDS) cases as model for the patients' response to treatments. Since organoids represent a model system comparable to patient-derived xenografts, the investigators tested the null hypothesis that the possibility of correctly identifying the drug-sensitivity could improve from 80%, as assessed by xenografts to at least 95%. The first step was planned to include 7 patients; if 5 or more patients do not respond, the trial will be terminated. If the trial goes on to the second stage, a total of 43 patients will be studied. Considering a patient dropout of approximately 10%, the study was planned to enroll at least 48 patients.

Detailed description: In this project, the investigators propose to employ the patients-derived organoid technology to test HGSOC organoids obtained from PDS+adjuvant chemotherapy and NACT+IDS cases to predict patients' response to treatments; moreover, the investigators aim to study genomic and phenotypic evolution of HGSOC organoids from PDS+adjuvant chemotherapy and NACT+IDS patients undergoing relapse. Finally, the investigators intend to investigate splicing-targeting technologies as new potential therapeutic treatments to increase vulnerability of HGSOCs. FIGO stage IIIC or IV ovarian, fallopian tube, or primary peritoneal cancer patients will be included if disease at metastatic sites is supposed to be completely resectable and they will be triaged for staging laparoscopy to obtain histologic diagnosis and to provide the tumor load assessment through the laparoscopic score. If PDS is chosen, open cytoreduction will be performed at the same time and bioptic tissue will be collected for organoids; otherwise, women will be submitted to NACT followed by IDS and tissue for organoids will be collected from both staging LPS biopsy (pre-) and subsequent surgery (post-NACT). Part of each surgical specimen will be used to obtain organoids, whereas part will be frozen for direct comparative analysis of the original tumor. 1-6 organoids from each patient will be prepared from PDS or NACT-IDS patients (pre- and post-NACT) and blood samples will also be collected to purify extracellular circulating RNA (cRNAs).

Eligibility criteria: Inclusion Criteria:

1. age between 18 and 75 years
2. estimated life expectancy of at least 4 weeks
3. performance status (PS) according to Eastern Cooperative Oncology Group (ECOG) \< 2
4. adequate bone marrow, respiratory, hepatic, cardiologic medullary and renal function (creatinine clearance \< 60 ml/min according to Cockroft formula)
5. histologic diagnose of epithelial ovarian cancer at frozen section and laparoscopic score ≥ 8 or ≤ 12 (considered HTL) with no evidence of mesenteric retraction

Exclusion Criteria:

1. Pregnancy or breast-feeding
2. History of concomitant or previous malignancy in the last 5 years

Primary outcomes:
measure: Reliability (yes/no) of HGSOC organoids obtained from PDS+adjuvant chemotherapy and NACT+IDS cases as a model for the patient's response to treatments
timeFrame: Up to 36 months
Secondary outcomes:
measure: The genomic and phenotypic evolution of tumor cells in HGSOC organoids from PDS+ adjuvant chemotherapy and NACT+IDS patients undergoing relapse
timeFrame: Up to 36 months
measure: Splicing dysregulation and splicing-targeting technologies as new potential therapeutic treatments to increase vulnerability of MYC-overexpressing HGSOCs
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario "A. Gemelli" IRCCS
Study officials:
affiliation: Fondazione Policlinico "A. Gemelli" IRCCS
name: Giuseppe Vizzielli, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione Policlinico "A. Gemelli" IRCCS - Università Cattolica del Sacro cuore
name: Giovanni Scambia, Professor
role: STUDY_DIRECTOR
affiliation: Catholic University of the Sacred Heart
name: Claudio Sette, Professor
role: STUDY_DIRECTOR
affiliation: Fondazione Policlinico "A. Gemelli" IRCCS
name: Camilla Nero, PhD
role: STUDY_CHAIR
affiliation: Catholic University of the Sacred Heart
name: Eleonari Cesari, PhD
role: STUDY_CHAIR
affiliation: Fondazione Policlinico "A. Gemelli" IRCCS
name: Salvatore Gueli Alletti, MD
role: STUDY_CHAIR
affiliation: Catholic University of the Sacred Heart
name: Marco Pieraccioli, PhD
role: STUDY_CHAIR
affiliation: Fondazione Policlinico "A. Gemelli" IRCCS
name: Carolina Bottoni, MD
role: STUDY_CHAIR
affiliation: Fondazione Policlinico "A. Gemelli" IRCCS
name: Carmine Conte, MD
role: STUDY_CHAIR
affiliation: Catholic University of the Sacred Heart
name: Matteo Loverro, MD
role: STUDY_CHAIR
affiliation: Catholic University of the Sacred Heart
name: Anna Fagotti, Professor
role: STUDY_CHAIR
References:
citation: Fagotti A, Ferrandina G, Vizzielli G, Fanfani F, Gallotta V, Chiantera V, Costantini B, Margariti PA, Gueli Alletti S, Cosentino F, Tortorella L, Scambia G. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome. Eur J Cancer. 2016 May;59:22-33. doi: 10.1016/j.ejca.2016.01.017. Epub 2016 Mar 19.
citation: Petrillo M, Zannoni GF, Beltrame L, Martinelli E, DiFeo A, Paracchini L, Craparotta I, Mannarino L, Vizzielli G, Scambia G, D'Incalci M, Romualdi C, Marchini S. Identification of high-grade serous ovarian cancer miRNA species associated with survival and drug response in patients receiving neoadjuvant chemotherapy: a retrospective longitudinal analysis using matched tumor biopsies. Ann Oncol. 2016 Apr;27(4):625-34. doi: 10.1093/annonc/mdw007. Epub 2016 Jan 17.
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citation: Ricci F, Bizzaro F, Cesca M, Guffanti F, Ganzinelli M, Decio A, Ghilardi C, Perego P, Fruscio R, Buda A, Milani R, Ostano P, Chiorino G, Bani MR, Damia G, Giavazzi R. Patient-derived ovarian tumor xenografts recapitulate human clinicopathology and genetic alterations. Cancer Res. 2014 Dec 1;74(23):6980-90. doi: 10.1158/0008-5472.CAN-14-0274. Epub 2014 Oct 10.
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