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.
Aperçu de l'étude
Statut
Intervention / Traitement
Description détaillée
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
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Coordonnées de l'étude
- Nom: Carl Brown
- Numéro de téléphone: 203-785-4096
- E-mail: carl.brown@yale.edu
Lieux d'étude
-
-
Connecticut
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New Haven, Connecticut, États-Unis, 06520
- Yale New Haven Hospital - Yale Cancer Center
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Diagnostique
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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 |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Number of participants with ESR1 mutations detected by reflex tissue NGS
Délai: 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)
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Progression-free survival (PFS)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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.
Délai: 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
Délai: 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
Délai: 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
Délai: 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
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Jing Du, MD, Yale University
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 2000038562
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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