Prospective Study to Evaluate the Clinical Utility of ctDNA Tumor Fraction (TF) for Detection of Estrogen Receptor 1 (ESR1) Mutations in (Human Epidermal Growth Factor Receptor) HR+/HER2- Metastatic Breast Cancer (MBC)
Prospective Study to Evaluate the Clinical Utility of ctDNA Tumor Fraction (TF) for Detection of ESR1 Mutations in HR-positive HER2-negative Metastatic Breast Cancer (MBC)
This is a prospective, single center, single-arm interventional study to evaluate the clinical utility of protocol-mandated diagnostic testing algorithm incorporating liquid biopsy and reflex tissue biopsy NGS for detection of ESR1 mutations in HR+/HER- metastatic breast cancer.
Přehled studie
Postavení
Detailní popis
Participants are prospectively assigned to undergo ctDNA testing with FoundationOne® Liquid CDx (F1LCDx) at protocol-defined clinical decision points. Participants with an indeterminate negative F1LCDx result (ctDNA TF <1% and negative for ESR1mut) are assigned to undergo reflex tissue biopsy NGS unless deemed medically unsafe. The protocol does not mandate treatment selection; treating clinicians retain full discretion regarding therapy.All research-related procedures will be performed at the time of standard of care clinical visits. No extra visits outside of routine care are required. For participants with algorithm-detected ESR1 mutations, serial Electronic Medical Record review will be performed for up to 2 years to track subsequent treatment patterns, progression events, and survival status to assess other clinical outcomes associated with subsequent SERD-based regimens compared with historical clinical trial benchmarks.
This study will guide clinical decision-making for acquiring new tissue specimens following an indeterminate negative ESR1mut result from liquid biopsy, which is a critical step to ensure accurate detection of actionable mutations and enable the selection of the most appropriate targeted therapy
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Carl Brown
- Telefonní číslo: 203-785-4096
- E-mail: carl.brown@yale.edu
Studijní místa
-
-
Connecticut
-
New Haven, Connecticut, Spojené státy, 06520
- Yale New Haven Hospital - Yale Cancer Center
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Diagnosis of metastatic breast cancer that is hormone receptor-positive (ER≥10%), HER2 low or negative (defined as HER2 Imunohistochemistry (IHC) 0, 1+ or IHC 2+/In Situ Hybridization (ISH)-).
- Progression of metastatic breast cancer that is hormone receptor-positive (ER≥10%), HER2 low or negative (defined as HER2 IHC 0, 1+ or IHC 2+/ISH-) while on systemic therapy.
- Currently receiving or have previously received aromatase inhibitor therapy.
Exclusion Criteria:
- Patients with locally or regionally recurrent breast cancer without evidence of metastatic disease.
- De novo metastatic breast cancer.
- Presence of symptomatic metastatic visceral crisis.
- Participants with inflammatory breast cancer.
- Intact uterus with a history of endometrial intraepithelial neoplasia (atypical endometrial hyperplasia or higher-grade lesion).
- Diagnosis of any other malignancy within 5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or second primary breast cancer.
- Other conditions that, in the opinion of the treating investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
- Pregnant and breastfeeding women are excluded from the study
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Diagnostický
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: HR+/HER- metastatic breast cancer at diagnosis or experiencing disease progression
Participants with ESR1 mutations in HR+/HER- metastatic breast cancer undergoing tissue biopsy for ctDNA Tumor Fraction (TF) testing using next-generation sequencing (NGS) after an indeterminate negative result in liquid biopsy (F1LCDx). |
Blood test that analyzes cancer-related genes from a single blood draw Reflex tissue biopsy using an Next-generation sequencing (NGS) test |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Number of participants with ESR1 mutations detected by reflex tissue NGS
Časové okno: From enrollment through study completion (up to 5 years)
|
Among participants with an indeterminate-negative liquid biopsy result (negative for ESR1 mutations and ctDNA tumor fraction below 1%), measure the number of participants with an ESR1 mutation detected by reflex tissue NGS performed according to the study algorithm. |
From enrollment through study completion (up to 5 years)
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Progression-free survival (PFS)
Časové okno: Up to 2 years after positive ESR1 mutation detection
|
Time from initiation of the first selective estrogen receptor degrader (SERD) after ESR1 mutation detection until objective disease progression, assessed using RECIST version 1.1 when available, or death from any cause, whichever occurs first. |
Up to 2 years after positive ESR1 mutation detection
|
|
Rate of ESR1 mutation detection by liquid biopsy and ctDNA tumor fraction
Časové okno: Throughout the study, up to 5 years
|
Rate of ESR1 mutation detection by FoundationOne Liquid CDx (F1LCDx), stratified by ctDNA tumor fraction below 1% versus 1% or greater. |
Throughout the study, up to 5 years
|
|
Reflex Tissue NGS testing rate
Časové okno: Within the reflex testing time frame during the study, up to 5 years
|
Number of participants with an indeterminate-negative liquid biopsy result who undergo reflex tissue biopsy and NGS within the protocol-defined timeframe. |
Within the reflex testing time frame during the study, up to 5 years
|
|
Number participants initiating Selective Estrogen Receptor Degraders (SERD) therapy
Časové okno: Throughout the study, up to 5 years
|
Number participants initiating SERD therapy after ESR1 mutation detection |
Throughout the study, up to 5 years
|
|
Number participants SERD therapy by SERD agent
Časové okno: Throughout the study, up to 5 years
|
Number participants initiating SERD therapy after ESR1 mutation detection. Report counts by SERD agent, with FDA-approved SERDs grouped by class as applicable. |
Throughout the study, up to 5 years
|
|
Actionable genomic alterations detected by liquid biopsy and tissue NGS.
Časové okno: Throughout the study, up to 5 years
|
Rtes of actionable genomic alterations detected by F1LCDx and tissue NGS. |
Throughout the study, up to 5 years
|
|
Other genomic alterations detected at disease progression
Časové okno: At disease progression during the study, up to 5 years
|
Rates of driver and acquired genomic alterations detected at progression by F1LCDx or tissue NGS that were absent from prior tissue comprehensive genomic profiling (CGP). Acquired alterations are those absent from tissue CGP at diagnosis but newly detected at progression. |
At disease progression during the study, up to 5 years
|
|
Correlation of HRR gene findings with variant origin and germline confirmation
Časové okno: During the study, when the relevant genomic and confirmatory testing results are available, up to 5 years
|
Assess the relationship between homologous recombination repair (HRR) gene detection, variant origin prediction, germline banner classification when F1LCDx is performed, and confirmation of germline alterations by orthogonal testing. |
During the study, when the relevant genomic and confirmatory testing results are available, up to 5 years
|
|
Correlation of HER2 status with ERBB2 copy number
Časové okno: During the study, when the relevant HER2 status and genomic results are available, up to 5 years
|
Assess the relationship between HER2-low or HER2-negative status and ERBB2 copy number results when F1CDx is performed. |
During the study, when the relevant HER2 status and genomic results are available, up to 5 years
|
Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Jing Du, MD, Yale University
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
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