ON-treatment Single-cell Analysis for the Identification of Early Tumor Response Biomarkers on Prospective Collected Serial Tumor Biopsies in Triple Negative Breast Cancer Patient During Standard Neoadjuvant Chemo-immunotherapy (ONSET)
This study explores early breast cancer, focusing on triple-negative and high-risk luminal subtypes. It combines single-cell RNA sequencing and spatial imaging of tumor samples collected at different time points during treatment. The aim is to better understand how cancer cells and immune cells interact and to identify biomarkers that can predict whether a patient will respond to chemo-immunotherapy or develop resistance.
The study assumes that early molecular and spatial changes at the single-cell level can predict treatment response. This knowledge could help doctors adapt therapies, avoiding unnecessary treatment while improving effectiveness. The project seeks to reveal, for the first time, how cellular diversity and spatial relationships contribute to treatment resistance and disease progression.
Tumor samples will be analyzed before treatment, after the first treatment cycle (C1D1), and at surgery. Only the biopsy taken after C1D1 is collected specifically for this study; all other samples come from routine clinical care.
Przegląd badań
Status
Interwencja / Leczenie
Szczegółowy opis
This exploratory translational study investigates early breast cancer (EBC), focusing on triple-negative (TNBC) and high-risk luminal (ER+/HER2-) subtypes. By integrating single-cell RNA sequencing, using the 10x Genomics platform (or similar technologies if it will be not available at the time of experiment), and spatial imaging analyses from serial tumor biopsies, the project aims to characterize tumor-immune interactions and identify predictive biomarkers of response or resistance to neoadjuvant chemo-immunotherapy.
We hypothesize that early molecular and spatial features, when detected at the single-cell level, can predict treatment sensitivity or resistance. This would enable adaptive therapeutic strategies that minimize overtreatment while maximizing efficacy in EBC. Our goal is to reveal, for the first time, the cellular heterogeneity and spatial interactions that drive therapy resistance and disease progression.
The analysis will be performed on tumor biopsies collected before the start of treatment, after C1D1 and on surgical material. The only tissue sample collected specifically for the study is the biopsy after C1D1.
Typ studiów
Zapisy (Szacowany)
Faza
- Nie dotyczy
Kontakty i lokalizacje
Kontakt w sprawie studiów
- Nazwa: Giulia Viale, MD
- Numer telefonu: +390226437627
- E-mail: callcenter.mammella@hsronline.it
Lokalizacje studiów
-
-
Lombardy
-
Milan, Lombardy, Włochy, 20132
- IRCCS Ospedale San Raffaele
-
Kontakt:
- Giulia Viale, MD
- Numer telefonu: +390226437627
- E-mail: callcenter.mammella@hsronline.it
-
-
Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
- Dorosły
- Starszy dorosły
Akceptuje zdrowych ochotników
Opis
Inclusion Criteria:
- Female patients aged ≥18 years.
- ECOG performance status 0-1.
Histologically confirmed early breast cancer with one of the following molecular profiles:
- TNBC: ER and PR negative (IHC <10%) and HER2 negative (IHC 0-1+ or FISH non-amplified).
- High-risk luminal (ER+/HER2-): ER positive (IHC ≥10%) HER2 negative (IHC 0-1+ or FISH non-amplified), with high-risk features (e.g., Grade 3, PR-negative, high proliferation, high TILS).
Clinical indication for neoadjuvant treatment according to standard practice:
- TNBC: cT1c and/or cN positive, or cT2 (>2 cm) and/or cN positive (stage II,III).
- High-risk luminal: features as defined above (Grade 3, PR-negative, high proliferation, ER low).
- Ability to understand and sign written informed consent for participation in the study, approved by the local Ethics Committee.
Exclusion Criteria:
- HER2-positive tumors.
- Multifocal tumors - exclusion if a single index lesion cannot be identified and sampled; otherwise allowed if a representative lesion can be biopsied.
- Known metastatic disease. 4 Clinical contraindications to the planned neoadjuvant therapy.
5. Decision for upfront surgery as determined by the multidisciplinary team. 6. Inability to provide informed consent. 7. Pregnancy or breastfeeding. 8. Prior systemic therapy (chemotherapy, immunotherapy, or endocrine therapy) for the current breast cancer before baseline biopsy 9. On-treatment biopsy clinically not feasible or controindicated
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Inny
- Przydział: Nie dotyczy
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
To characterize the dynamic changes in tumor and immune cell populations in TNBC and to prospectively collect serial samples from high-risk luminal (ER+/HER2-) breast cancer patients.
Ramy czasowe: Pre-treatment, on-treatment (after first cycle of therapy), and post-treatment (surgery or residual disease)
|
Gene expression levels per single-cell and relative cell clustering (%) by comparing pre-treatment, on-treatment (after first cycle of standard of care neoadiuvant therapy), and post-treatment (surgery or residual disease)
|
Pre-treatment, on-treatment (after first cycle of therapy), and post-treatment (surgery or residual disease)
|
Inne miary wyników
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
To correlate single-cell gene expression data with pCR and RD to identify predictive signatures of therapy response
Ramy czasowe: Across all collected timepoints (baseline, after C1 of neadiuvant standard of care therapy and at surgery)
|
pCR and RD will be evaluated across all collected timepoints (baseline, after C1 of neadiuvant standard of care therapy and at surgery)
|
Across all collected timepoints (baseline, after C1 of neadiuvant standard of care therapy and at surgery)
|
Współpracownicy i badacze
Sponsor
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Szacowany)
Zakończenie podstawowe (Szacowany)
Ukończenie studiów (Szacowany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- ONSET
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .
Badania kliniczne na Rak piersi Rak piersi we wczesnym stadium (stadium 1-3)
-
University of Michigan Rogel Cancer CenterNational Cancer Institute (NCI)Jeszcze nie rekrutacjaSyndrom Lyncha | Dziedziczny zespół nowotworowy | BRCA1-Related Hereditary Breast and Ovarian Cancer Syndrome | BRCA2-Related Hereditary Breast and Ovarian Cancer SyndromeStany Zjednoczone