Translational Analysis In Longitudinal Series of Ovarian Cancer ORganoids

NCT04555473 | Unknown

• 1 other identifier: TAILOR
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Organoids; Epithelial Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  Part of each surgical specimen of eligible women will be used to obtain PDOs according to established protocols (Tuveson et al.), whereas part will be frozen for direct comparative analysis of the original tumor. At first passages, organoids will be characterized for histologic and cytologic features. PDOs maintaining HGSOC features will be analysed for genomic features and splicing-sensitive transcriptomic signatures by next generation sequencing (NGS). The identified transcriptomic signatures of PDOs will be compared to those of the original tumor by quantitative real time PCR (qPCR) analysis. PDOs will then be characterized for their response to specific drugs and the response will be compared to that of the patient undergoing chemotherapy. Dichotomic variable: Yes/No

  Up to 36 months

Secondary Outcomes (2)

• The genomic and phenotypic evolution of tumor cells in HGSOC organoids from PDS+ adjuvant chemotherapy and NACT+IDS patients undergoing relapse

  Up to 36 months

• Splicing dysregulation and splicing-targeting technologies as new potential therapeutic treatments to increase vulnerability of MYC-overexpressing HGSOCs

  Up to 36 months

Interventions

Tumor biopsy PROCEDURE

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).

Also known as: Blood sampling

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: Female patients
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• Pregnancy or breast-feeding
• History of concomitant or previous malignancy in the last 5 years

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario "A. Gemelli" IRCCS

Rome, 00168, Italy

RECRUITING

Related Publications (6)

• 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.

  PMID: 26998845 RESULT

• 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.

  PMID: 26782955 RESULT

• 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.

  PMID: 24849521 RESULT

• 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.

  PMID: 30213835 RESULT

• 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.

  PMID: 25304260 RESULT

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

  PMID: 31171691 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Bioptic tissue from the tumor will be collected from PDS and NACT+IDS patients at the time of surgery. Part of the bioptic tissue will be used to obtain organoids, whereas part will be frozen for direct comparative analysis of the original tumor. Blood samples will also be collected to purify extracellular circulating RNA (cRNAs).

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Giuseppe Vizzielli, PhD

  Fondazione Policlinico "A. Gemelli" IRCCS

  PRINCIPAL INVESTIGATOR

• Giovanni Scambia, Professor

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

  STUDY DIRECTOR

• Claudio Sette, Professor

  Catholic University of the Sacred Heart

  STUDY DIRECTOR

• Camilla Nero, PhD

  Fondazione Policlinico "A. Gemelli" IRCCS

  STUDY CHAIR

• Eleonari Cesari, PhD

  Catholic University of the Sacred Heart

  STUDY CHAIR

• Salvatore Gueli Alletti, MD

  Fondazione Policlinico "A. Gemelli" IRCCS

  STUDY CHAIR

• Marco Pieraccioli, PhD

  Catholic University of the Sacred Heart

  STUDY CHAIR

• Carolina Bottoni, MD

  Fondazione Policlinico "A. Gemelli" IRCCS

  STUDY CHAIR

• Carmine Conte, MD

  Fondazione Policlinico "A. Gemelli" IRCCS

  STUDY CHAIR

• Matteo Loverro, MD

  Catholic University of the Sacred Heart

  STUDY CHAIR

• Anna Fagotti, Professor

  Catholic University of the Sacred Heart

  STUDY CHAIR

Central Study Contacts

Giuseppe Vizzielli, PhD

CONTACT

3403990822; giuseppe.vizzielli@policlinicogemelli.it

Giuseppe Vizzielli, PhD

CONTACT

3403990822; giuseppevizzielli@yahoo.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2020
• First Posted: September 18, 2020
• Study Start: May 12, 2020
• Primary Completion: November 4, 2021
• Study Completion: May 4, 2023
• Last Updated: September 18, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)