Translational Analysis In Longitudinal Series of Ovarian Cancer ORganoids (TAILOR)

September 14, 2020 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
      • Rome, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario "A. GEMELLI" IRCCS
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The genomic and phenotypic evolution of tumor cells in HGSOC organoids from PDS+ adjuvant chemotherapy and NACT+IDS patients undergoing relapse
Time Frame: Up to 36 months
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
Up to 36 months
Splicing dysregulation and splicing-targeting technologies as new potential therapeutic treatments to increase vulnerability of MYC-overexpressing HGSOCs
Time Frame: Up to 36 months
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
Up to 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Giuseppe Vizzielli, PhD, Fondazione Policlinico "A. Gemelli" IRCCS
  • Study Director: 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 Chair: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 12, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 4, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 4, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 25, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 18, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 18, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TAILOR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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