Translational Analysis In Longitudinal Series of Ovarian Cancer ORganoids

NCT ID: NCT04555473

Last Updated: 2020-09-18

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 48 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-05-12
• Study Completion Date: 2023-05-04

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).

Conditions

Organoids; Epithelial Ovarian Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Tumor biopsy

Both interventions performed at baseline upon study enrolment (pre- and post-NACT for NACT+IDS patients) and at the time of recurrence.

1. 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).

2. Blood samples will be collected to purify extracellular circulating RNA (cRNAs).

Intervention Type: PROCEDURE

Other Intervention Names

Blood sampling

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giuseppe Vizzielli, PhD

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico "A. Gemelli" IRCCS

Giovanni Scambia, Professor

Role: STUDY_DIRECTOR

Fondazione Policlinico "A. Gemelli" IRCCS - Università Cattolica del Sacro cuore

Claudio Sette, Professor

Role: STUDY_DIRECTOR

Catholic University of the Sacred Heart

Camilla Nero, PhD

Role: STUDY_CHAIR

Fondazione Policlinico "A. Gemelli" IRCCS

Eleonari Cesari, PhD

Role: STUDY_CHAIR

Catholic University of the Sacred Heart

Salvatore Gueli Alletti, MD

Role: STUDY_CHAIR

Fondazione Policlinico "A. Gemelli" IRCCS

Marco Pieraccioli, PhD

Role: STUDY_CHAIR

Catholic University of the Sacred Heart

Carolina Bottoni, MD

Role: STUDY_CHAIR

Fondazione Policlinico "A. Gemelli" IRCCS

Carmine Conte, MD

Role: STUDY_CHAIR

Fondazione Policlinico "A. Gemelli" IRCCS

Matteo Loverro, MD

Role: STUDY_CHAIR

Catholic University of the Sacred Heart

Anna Fagotti, Professor

Role: STUDY_CHAIR

Catholic University of the Sacred Heart

Locations

Fondazione Policlinico Universitario "A. Gemelli" IRCCS

Rome, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Giuseppe Vizzielli, PhD

Role: CONTACT

giuseppe.vizzielli@policlinicogemelli.it

3403990822 ext. 0039

Giuseppe Vizzielli, PhD

Role: CONTACT

giuseppevizzielli@yahoo.it

3403990822 ext. 0039

Facility Contacts

Giuseppe Vizzielli, PhD

Role: primary

giuseppevizzielli@yahoo.it

References

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.

Reference Type: RESULT

PMID: 26998845 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26782955 (View on PubMed)

Vizzielli G, Costantini B, Tortorella L, Petrillo M, Fanfani F, Chiantera V, Ercoli A, Iodice R, Scambia G, Fagotti A. Influence of intraperitoneal dissemination assessed by laparoscopy on prognosis of advanced ovarian cancer: an exploratory analysis of a single-institution experience. Ann Surg Oncol. 2014 Nov;21(12):3970-7. doi: 10.1245/s10434-014-3783-6. Epub 2014 May 22.

Reference Type: RESULT

PMID: 24849521 (View on PubMed)

Hill SJ, Decker B, Roberts EA, Horowitz NS, Muto MG, Worley MJ Jr, Feltmate CM, Nucci MR, Swisher EM, Nguyen H, Yang C, Morizane R, Kochupurakkal BS, Do KT, Konstantinopoulos PA, Liu JF, Bonventre JV, Matulonis UA, Shapiro GI, Berkowitz RS, Crum CP, D'Andrea AD. Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids. Cancer Discov. 2018 Nov;8(11):1404-1421. doi: 10.1158/2159-8290.CD-18-0474. Epub 2018 Sep 13.

Reference Type: RESULT

PMID: 30213835 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25304260 (View on PubMed)

Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019 Jun 7;364(6444):952-955. doi: 10.1126/science.aaw6985.

Reference Type: RESULT

PMID: 31171691 (View on PubMed)

Other Identifiers

TAILOR

Identifier Type: -

Identifier Source: org_study_id