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.
調査の概要
状態
詳細な説明
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
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Carl Brown
- 電話番号：203-785-4096
- メール：carl.brown@yale.edu
研究場所
-
-
Connecticut
-
New Haven、Connecticut、アメリカ、06520
- Yale New Haven Hospital - Yale Cancer Center
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：診断
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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 |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of participants with ESR1 mutations detected by reflex tissue NGS
時間枠：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)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression-free survival (PFS)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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.
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 2000038562
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