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OrganoidsTAILORNCT04555473

Translational Analysis In Longitudinal Series of Ovarian Cancer ORganoids

An observational study of Organoids and Epithelial Ovarian Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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'… Read more about this study

Who is it for?
Ages 18 to 75 years, women only
Conditions the study is for
Organoids, Epithelial Ovarian Cancer
What is being tested?
Tumor biopsy
Type of treatment
Surgery or procedure
How many people
48 participants
Where
1 siteItaly
Study dates
12 May 2020to 4 May 2023
How long will I take part?
36 Months
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Italy1 site, 1 recruiting
  • Fondazione Policlinico Universitario "A. Gemelli" IRCCS

    Rome, 00168

    Giuseppe Vizzielli, PhD, giuseppevizzielli@yahoo.it

    Recruiting

Other trials in Italy

About this study

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.

Read the 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).

Being tested
Tumor biopsy
Medical subject headings
Carcinoma, Ovarian Epithelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tumor biopsyProcedure or surgery

    Also called Blood sampling

    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).

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 36 months

Secondary outcomes (2)
  1. The genomic and phenotypic evolution of tumor cells in HGSOC organoids from PDS+ adjuvant chemotherapy and NACT+IDS patients undergoing relapse

    At time of relapse (if any), we will repeat NGS genomic and transcriptomic analysis of chemoresistant PDOs derived from selected patients who experienced relapse and underwent secondary surgery. Bioinformatics analyses will be applied to capture changes in the mutational status and in the transcriptional/splicing signature that accompany acquisition of chemoresistance in vitro. These features will then be compared to evolution of the tumor in vivo by sequencing (mutations) and qPCR (transcriptomics) of tissue obtained during surgery. Dichotomic variable: Yes/No

    Measured: Up to 36 months

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

    HGSOCs often display amplification of MYC, an oncogene that dysregulates the splicing program. We will test if HGSOC PDOs are sensitive to splicing-targeting drugs (E7107, THZ531, PRMT5 inhibitor) administered either alone or in combination with chemotherapy. THZ531 renders BRCA1/2 proficient HGSOC cell lines sensitive to PARPi. We will extend this study to PDOs and analyze their sensitivity to splicing-targeting drugs during their evolution in vitro. Changes in splicing signatures will be evaluated and correlated with the response to combined treatments, to determine their potential as biomarkers. We will also silence splicing factors deregulated in HGSOCs by RNA interference to determine their impact on PDO response to chemotherapy in terms of survival, expansion potential and transcriptomic signatures. Dichotomic variable: Yes/No

    Measured: Up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2020
  2. Study start12 May 2020
  3. Primary completion4 Nov 2021 (estimated)
  4. Study completion4 May 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
48 participants (estimated)
Target duration
36 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT04555473
Sponsor's protocol ID
TAILOR
Acronym
TAILOR
Status last verified
Apr 2020
First submitted
25 May 2020
Last updated
18 Sep 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 26998845
  • 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.

    PubMed 26782955
  • 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.

    PubMed 24849521
  • 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.

    PubMed 30213835
  • 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.

    PubMed 25304260
  • Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019 Jun 7;364(6444):952-955. doi: 10.1126/science.aaw6985.

    PubMed 31171691

Questions about this trial

What is this clinical trial studying?

An observational study of Organoids and Epithelial Ovarian Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Giuseppe Vizzielli, PhD (3403990822 ext. 0039, giuseppe.vizzielli@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04555473, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2020.

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