Breast Cancer Subtype Characterization Through Patient's Derived Organoids.
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-70
SponsorFondazione Policlinico Universitario Agostino Gemelli IRCCS
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
women diagnosed with primary BC, eligible for surgical resection of the tumor according to national and international guidelines.
Disqualifiers
None
Trial 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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
No trial groups listed
Trial outcomes
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.
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)
Time frame
36 months2
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)
Time frame
42 monthsSecondary outcomes
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.
Time frame
42 months2
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
Time frame
42 monthsSponsors and contacts
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Source ClinicalTrials.gov