AzTrials
AzTrials

Breast CancerBCinsightPDONCT06315868

Breast Cancer Subtype Characterization Through Patient's Derived Organoids.

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

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Breast Cancer, Organoids
How many people
306 participants
Where
1 siteItaly
Study dates
15 Jun 2023to 15 Jun 2027
How long will I take part?
5 Years
Phase
Observational
Are there results?
Not yet: the study is under way

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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.

Who cannot join

  • breast cancer diagnosed during pregnancy, neoadiuvant chemotherapy

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Alba Di Leone, Doc contact

0039 3474980503

alba.dileone@policlinicogemelli.it

Chiara Naro, Doc contact

0039 3495087203

chiara.naro@unicatt.it

Italy1 site, 1 recruiting

  • IRCCS Fondazione Policlinico A. Gemelli

    Roma, 00168

    alba di leone, MD, 0039 3474980503, alba.dileone@policlinicogemelli.it

    Recruiting

Other trials in Italy

About this study

Official title: 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

Read the 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.

Keywords
breast cancer, new drugs, organoids
Medical subject headings
Breast Neoplasms

What is being measured

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

  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.

    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)

    Measured: 36 months

  2. evaluate the sensitivity of ER/PR+, HER2+ and TNBC PDO to novel therapeutic agents in clinical trials for BC or other cancer types

    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)

    Measured: 42 months

Secondary outcomes (2)

  1. test the sensitivity of PDO to splicing-targeting treatments, either alone or in combination with other therapies

    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.

    Measured: 42 months

  2. test the synergizing effects of agents splicing-targeting treatments to immunotherapies by co-culture experiments with autologous immune cells

    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

    Measured: 42 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 Mar 2024
  2. Study start15 Jun 2023
  3. Primary completion15 Jun 2026 (estimated)
  4. Study completion15 Jun 2027 (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
306 participants (estimated)
Target duration
5 Years
IDs, dates and publications
ClinicalTrials.gov ID
NCT06315868
Sponsor's protocol ID
5590
Acronym
BCinsightPDO
Status last verified
Jun 2023
First submitted
11 May 2023
Last updated
18 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Harbeck N, Gnant M. Breast cancer. Lancet. 2017 Mar 18;389(10074):1134-1150. doi: 10.1016/S0140-6736(16)31891-8. Epub 2016 Nov 17.

    PubMed 27865536

  • Garrido-Castro AC, Lin NU, Polyak K. Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment. Cancer Discov. 2019 Feb;9(2):176-198. doi: 10.1158/2159-8290.CD-18-1177. Epub 2019 Jan 24.

    PubMed 30679171

  • Denkert C, Liedtke C, Tutt A, von Minckwitz G. Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet. 2017 Jun 17;389(10087):2430-2442. doi: 10.1016/S0140-6736(16)32454-0. Epub 2016 Dec 7.

    PubMed 27939063

  • Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1275-81. doi: 10.1200/JCO.2007.14.4147. Epub 2008 Feb 4.

    PubMed 18250347

  • Kornblihtt AR, Schor IE, Allo M, Dujardin G, Petrillo E, Munoz MJ. Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat Rev Mol Cell Biol. 2013 Mar;14(3):153-65. doi: 10.1038/nrm3525. Epub 2013 Feb 6.

    PubMed 23385723

  • Pagliarini V, Naro C, Sette C. Splicing Regulation: A Molecular Device to Enhance Cancer Cell Adaptation. Biomed Res Int. 2015;2015:543067. doi: 10.1155/2015/543067. Epub 2015 Jul 26.

    PubMed 26273627

  • Chabot B, Shkreta L. Defective control of pre-messenger RNA splicing in human disease. J Cell Biol. 2016 Jan 4;212(1):13-27. doi: 10.1083/jcb.201510032.

    PubMed 26728853

  • Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR. The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol. 2007 Mar;14(3):185-93. doi: 10.1038/nsmb1209. Epub 2007 Feb 18.

    PubMed 17310252

  • Hsu TY, Simon LM, Neill NJ, Marcotte R, Sayad A, Bland CS, Echeverria GV, Sun T, Kurley SJ, Tyagi S, Karlin KL, Dominguez-Vidana R, Hartman JD, Renwick A, Scorsone K, Bernardi RJ, Skinner SO, Jain A, Orellana M, Lagisetti C, Golding I, Jung SY, Neilson JR, Zhang XH, Cooper TA, Webb TR, Neel BG, Shaw CA, Westbrook TF. The spliceosome is a therapeutic vulnerability in MYC-driven cancer. Nature. 2015 Sep 17;525(7569):384-8. doi: 10.1038/nature14985. Epub 2015 Sep 2.

    PubMed 26331541

  • Chan S, Sridhar P, Kirchner R, Lock YJ, Herbert Z, Buonamici S, Smith P, Lieberman J, Petrocca F. Basal-A Triple-Negative Breast Cancer Cells Selectively Rely on RNA Splicing for Survival. Mol Cancer Ther. 2017 Dec;16(12):2849-2861. doi: 10.1158/1535-7163.MCT-17-0461. Epub 2017 Sep 6.

    PubMed 28878028

  • Stricker TP, Brown CD, Bandlamudi C, McNerney M, Kittler R, Montoya V, Peterson A, Grossman R, White KP. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression. PLoS Genet. 2017 Mar 6;13(3):e1006589. doi: 10.1371/journal.pgen.1006589. eCollection 2017 Mar.

    PubMed 28263985

  • Trincado JL, Sebestyen E, Pages A, Eyras E. The prognostic potential of alternative transcript isoforms across human tumors. Genome Med. 2016 Aug 17;8(1):85. doi: 10.1186/s13073-016-0339-3.

    PubMed 27535130

  • Kahles A, Lehmann KV, Toussaint NC, Huser M, Stark SG, Sachsenberg T, Stegle O, Kohlbacher O, Sander C; Cancer Genome Atlas Research Network; Ratsch G. Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients. Cancer Cell. 2018 Aug 13;34(2):211-224.e6. doi: 10.1016/j.ccell.2018.07.001. Epub 2018 Aug 2.

    PubMed 30078747

Questions about this trial

What is this clinical trial studying?

An observational study of Breast Cancer and Organoids, 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 2 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 18 Mar 2024. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Alba Di Leone, Doc (0039 3474980503, alba.dileone@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. 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 NCT06315868, which also lists 13 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 Mar 2024.

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