neoAGORA: A Prospective Observational Study to Explore the Clinical Utility of Serial Liquid Biopsy in Patients With Early-stage Breast Cancer Receiving Neoadjuvant Therapy.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 300
- 试验地点
- 10
- 主要终点
- Prognostic and Predictive Value of ctDNA in Patients Receiving NAT
研究概览
简要总结
The goal of this observational study is to explore the utility of analytical techniques that enable the study of small amounts of tumor-derived material circulating in the blood, such as fragments of circulating tumor DNA (also known as ctDNA), cells, or other particles. This type of sample is generally referred to as a liquid biopsy, and its analysis is a minimally invasive test, as it only requires the collection of blood samples. The study includes women and men with early-stage breast cancer (EBC) who are about to start neoadjuvant treatment (treatment given before surgery). The main questions it aims to answer are:
- Can liquid biopsy analyses (ctDNA) provide additional information about the type of tumor before treatment starts?
- Can these analyses help to detect early whether the tumor is responding to treatment?
- Can these tests identify if any cancer remains after neoadjuvant treatment or after surgery?
- Is this information related to the risk of the cancer coming back?
- Can these analyses, when performed during follow-up, help detect cancer recurrence earlier?
Participants will:
- Continue receiving standard medical care for their breast cancer, including neoadjuvant therapy and surgery.
- Provide blood samples at different time points during treatment and follow-up.
- Provide residual tumor samples from the routine clinical care.
详细描述
Study Rationale:
Neoadjuvant therapy (NAT) is a standard treatment approach for patients with early-stage breast cancer (EBC), its benefits extend beyond enabling breast conserving surgery: it provides an early dynamic assessment of treatment sensitivity and creates an in vivo framework to interrogate tumor biology under therapeutic pressure. Pathological complete response (pCR) is an established surrogate marker of prognosis, particularly in triple negative (TN) and Human Epidermal Growth Factor Receptor 2(HER2)-positive breast cancer; however, the ability to predict response early during treatment and to identify patients at risk of residual disease or relapse remains limited.
Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for monitoring tumor burden and treatment response in real time. Previous studies have shown that baseline ctDNA levels, early ctDNA clearance during NAT, and postoperative ctDNA detection are associated with treatment response, minimal residual disease (MRD), and relapse risk. Nevertheless, the clinical utility of ctDNA across breast cancer subtypes and its integration into routine clinical decision-making remain incompletely defined.
The neoAGORA study aims to evaluate subtype-specific ctDNA dynamics during standard NAT and to investigate their relationship with clinical outcomes, pathological response, advanced imaging findings, and digital pathology assessments. By integrating these complementary sources of information, the study seeks to improve response assessment and support the development of personalized management strategies for patients with EBC.
Study design:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent prior to any specific study procedure.
- •Patients with willingness and ability to comply with study procedures.
- •Patients (women and men) ≥18 years of age.
- •Patients with a first diagnosis of the UICC (Union for International Cancer Control) stage I-III primary invasive BC whose tumors are of any of the following subtypes:
- •Luminal: Hormonal Receptor(HR)-positive and HER2-negative.
- •HER2-positive: HER2-positive regardless of the HR status.
- •Triple negative: Hormonal Receptor(HR)-negative and HER2-negative. HR and HER2 status should be based on local laboratory determination following the criteria of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) international guidelines in effect at the time of testing.
- •Patients that are scheduled to receive NAT as determined by the treating physician according to standard clinical practice.
- •Archival Formalin-Fixed, Paraffin-Embedded (FFPE) sample of the primary tumor must be available to analyze tumor-informed ctDNA assays.
排除标准
- •Patients with stage IV BC.
- •Patients with previous anti-cancer treatment for the current BC.
- •Patients with diagnosis of any other invasive malignancy in the 5 prior years, unless the malignancy has been treated with curative intent and is considered at low risk of recurrence, with no evidence of active disease at study entry.
- •Patients with a diagnosis of bilateral or multifocal breast tumors with different HR or HER2 status.
- •Patients with any severe acute or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- •Patients who are concurrently enrolled in clinical trials.
- •Females who are pregnant or breastfeeding.
结局指标
主要结局
Prognostic and Predictive Value of ctDNA in Patients Receiving NAT
时间窗: From Study Start Date to Primary Completion Date (25 months).
To evaluate the association between ctDNA detection, molecular profiling, and longitudinal ctDNA dynamics (at baseline, during NAT and pre-surgery) and efficacy outcomes. The ctDNA metrics and patterns assessed before surgery will be: * ctDNA status/levels and molecular profiling at baseline, during NAT and post-NAT (pre-surgery), * early ctDNA dynamics during NAT (e.g. clearance vs. persistence), * ctDNA dynamics patterns post-NAT (pre-surgery) (e.g. clearance, persistence, rebound). Specific objectives: * To evaluate the association between the ctDNA metrics and patterns detailed in the protocol. * To derive candidate early ctDNA change thresholds during NAT and estimate their predictive and prognostic value.
次要结局
- Prognostic and predictive value of molecular residual disease (MRD) assessed by ctDNA(From Study Start Date to Study Completion Date (84 months).)
- Characterization of tumor evolution(From Study Start Date to Study Completion Date (84 months).)
- Biomarker discovery(From Study Start Date to Study Completion Date (84 months).)
- Reduction in the need for invasive procedures(From Study Start Date to Study Completion Date (84months).)
- Imaging predictions of tumor response and disease relapse(From Study Start Date to Study Completion Date (84 months). This will only be conducted if funding is obtained.)
- Multimodal integration: ctDNA, imaging, and digital pathology readouts(From Study Start Date to Study Completion Date (84 months).)
- Effectiveness in routine clinical practice(From Study Start Date to Study Completion Date (84 months).)
- Pharmacoeconomics(From Study Start Date to Study Completion Date (84 months). This will only be conducted if funding is obtained.)