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NCT Number: NCT06315868

Breast Cancer Subtype Characterization Through Patient's Derived Organoids.

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

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Organoids Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Observational

Primary location

IRCCS Fondazione Policlinico A. Gemelli

Roma, 00168, Italy

Location status: Recruiting

Location contact

alba di leone, MD

CONTACT

[email protected]

0039 3474980503

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. 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)

  2. 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)

Secondary outcomes

  1. 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.

  2. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Alba Di Leone, Doc

CONTACT

[email protected]

0039 3474980503

Chiara Naro, Doc

CONTACT

[email protected]

0039 3495087203

Sponsors and collaborators

Lead sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Other

Registry information

Official study title

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

Acronym: BCinsightPDO

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Mar 18, 2024
Registry last updated
Mar 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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