Breast Cancer Subtype Characterization Through Patient's Derived Organoids. (BCinsightPDO)

March 11, 2024 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Breast Cancer Subtype Characterization Through Patient's Derived Organoids". (BCinsightPDO)

Development of tools to predict patients chemo-sensitivity and identification of corresponding biomarkers is an urgent challenge for BC patients lacking targeted therapies, such as TNBC, or for patients experiencing relapse after adjuvant chemotherapy or targeted therapies.

The refinement of 3D-cultivation techniques, experienced in the last decade, has allowed cultivation of patients-derived cancer cells in organotypic structures, named patient-derived organoids (PDO), which preserve histologic, genomic and transcriptomic features of primary tumors. PDO allow propagation, pharmacological treatment and genetic manipulation of patients-derived cancer cells in a close to physiology setting, thus representing a promising tool in the development of personalized therapies

Study Overview

Status

Recruiting

Conditions

Detailed Description

PDO have been shown to efficiently recapitulate ex-vivo the in vivo response to hormonal treatment of BC patients. These observations point to PDO as potential valuable tools for a rapid, personalized prospective evaluation of patient-specific chemo-sensitivity. Moreover, PDO can represent a valuable ex-vivo platform for screening new treatments, or combination of current treatments, in a medium-to-high-throughput fashion. Thus, development of a stable collection of PDO representing the heterogeneity of BC subtypes, including the evolution of recurrent disease, represents an extremely useful resource for both prospective and retrospective studies aimed at understanding the molecular phenotype associated with chemoresistance.

Study Type

Observational

Enrollment (Estimated)

306

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 Backup

Study Locations

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Eligible population includes women diagnosed with primary BC, eligible for surgical resection of the tumor according to national and international guidelines. Each case will be discussed, before surgery, at the multidisciplinary tumor board for BC of the Fondazione Policlinico A. Gemelli, IRCCS.

All women will be required to sign written informed consent to enter the study. The study design has considered following inclusion criteria: age between 18 and 70 years; newly diagnosed breast neoplasms, tumor size of at least 1.5 cm diameter.

Description

Inclusion Criteria:

  • women diagnosed with primary BC, eligible for surgical resection of the tumor according to national and international guidelines.

age between 18 and 70 years; newly diagnosed breast neoplasms, tumor size of at least 1.5 cm diameter.

Exclusion Criteria:

breast cancer diagnosed during pregnancy, neoadiuvant chemotherapy

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
evaluate the histological and molecular conformity (yes/no) between PDO and matched primary and/or recurrent BC sample, in order to develop a live biobank of ER/PR+, HER2+ and TNBC PDO.
Time Frame: 36 months
Part of each surgical specimen will be used to obtain PDOs according to established procedures, part will be fixed and paraffin embedded for histological analysis and part will be flash-frozen for DNA, RNA and protein analyses. At first passages, organoids will be characterized for histologic and cytologic features. PDOs that faithfully recapitulate features of the matched primary tumor will be analysed for genomic features and splicing-sensitive transcriptomic signatures by next generation sequencing (NGS). Dichotomic variable: Yes (conform)/No (not conform)
36 months
evaluate the sensitivity of ER/PR+, HER2+ and TNBC PDO to novel therapeutic agents in clinical trials for BC or other cancer types
Time Frame: 42 months
PDO will be tested for their susceptibility to the therapeutic agents administered to the corresponding patients and/or to novel therapeutic agents in clinical trials for BC or other cancer types by performing cell viability assays and clonogenic potential assay before and after treatments. Sensitivity to the tested drugs will be evaluated on the basis of the known maximal plasma concentration of the drug (Cmax): sensitive if survival is <50% at Cmax dose; resistant if survival is >50% at Cmax dose. Dichotomic variable: Yes (sensitive)/No (resistant)
42 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
test the sensitivity of PDO to splicing-targeting treatments, either alone or in combination with other therapies
Time Frame: 42 months
PDO derived from primary and recurrent BC patients will be evaluated for sensitivity to splicing-targeting drugs, administered either alone or in combination with standard chemotherapy. Sensitivity to the splicing-targeting drugs tested will be evaluated on the basis of the known EC50 of the drug for its molecular target: sensitive if survival is <50% at EC50 dose; resistant if survival is >50% at EC50 dose. Dichotomic variable: Yes (sensitive)/No (resistant). Combination index (CI) will be evaluated to assess synergic effects, with CI < 1 indicates synergism.
42 months
test the synergizing effects of agents splicing-targeting treatments to immunotherapies by co-culture experiments with autologous immune cells
Time Frame: 42 months
PDO treated or not with the selected splicing inhibitor(s) will be exposed to PMBCs from the same patient previously stored under viable conditions, in presence or not of clinically available immune checkpoint inhibitors (anti-PD1 and anti-PD-L1 antibodies). Survival and proliferation assays will assess if treatment enhances the cytotoxic activity of PBMC towards cancer cells. Dichotomic variable: Yes/No
42 months

Collaborators and Investigators

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

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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)

June 15, 2023

Primary Completion (Estimated)

June 15, 2026

Study Completion (Estimated)

June 15, 2027

Study Registration Dates

First Submitted

May 11, 2023

First Submitted That Met QC Criteria

March 11, 2024

First Posted (Actual)

March 18, 2024

Study Record Updates

Last Update Posted (Actual)

March 18, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5590

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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