Evaluation of Circulating Tumor DNA Dynamics for Treatment Optimization in Stage II-III HER2-Positive and Triple-Negative Breast Cancer Candidate to NAT
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 186
- 主要终点
- Longitudinal assessment of ctDNA clearance (yes/no) across the three study cohorts following the completion of the first neoadjuvant treatment block. Clearance milestones are tailored to specific regimens: pre-anthracycline exposure for Cohort A, after 6
研究概览
简要总结
The purpose of this non-interventional, observational study is to evaluate the clinical utility of circulating tumor DNA (ctDNA) utility-specifically how quickly tumor DNA disappears from the bloodstream (ctDNA clearance)-to help monitor and predict treatment responses in patients with breast cancer.
The study focuses on patients diagnosed with Stage II to III HER2-positive or Triple-Negative Breast Cancer (TNBC) who are scheduled to receive standard neoadjuvant therapy (systemic treatment administered before surgery). Because these breast cancer subtypes involve different standard treatment regimens, the study prospectively stratifies patients into three distinct treatment cohorts (Cohorts A, B, and C) to match routine clinical practice and align blood sampling with meaningful clinical milestones.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with documented stage II-III HER2+ or TNBC and fit candidates for NAT.
- •In TNBC group, confirmed negative ER, PR and HER2 disease by local testing on primary disease specimen: tumor must be negative ER, PR, and HER2 defined by immunohistochemistry (IHC) according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing (Allison et al., 2020; Wolff et al., 2023).
- •In HER2+ group, Confirmed HER2+ disease by local testing on primary disease specimen: tumour must be HER2+ according to ASCO/CAP 2023 guidelines for HER2 testing (Wolff et al., 2023).
- •Patients with measurable disease; Patients with multifocal or multicentric breast cancer with at least one tumor lesion ≥1.0 cm in the longest diameter by ultrasound (reference lesion) are also eligible if the two largest tumor lesions have been histologically confirmed in the clinical evaluation and meet pathological criteria for TNBC and HER2+.
- •No previous treatment of the disease by chemotherapy, hormone therapy, surgery or radiotherapy.
- •Patients with breast cancer are eligible for surgery.
- •Eastern Cooperative Oncology Group (ECOG) performance status≤2.
排除标准
- •1. Patients with bilateral invasive BC.
- •Patients with metastatic BC (local spread to axillary lymph nodes is permitted (cN1_cN2a).
- •3. Patients with inflammatory BC.
- •Patients with a known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including hepatitis.
- •Patients with a history of invasive BC, ductal carcinoma in situ or lobular carcinoma in situ, and other malignancy within 5 years prior to screening.
- •Patients with a documented history of haemorrhagic diathesis, coagulopathy, or thromboembolism.
- •Patients with known allergy or hypersensitivity to any of the study drugs or any of their excipients.
- •Patients with history of non-compliance to medical regimens.
- •Patients refusing to perform liquid and tissue biopsy.
- •Patients unwilling to or unable to comply with the protocol.
- •Patients having had major surgery within 14 days prior to screening.
- •Pregnant or lactating females prior to treatment.
- •Patients should be excluded if they have a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
研究组 & 干预措施
Cohort A
Patients with stage II-III HER2-positive or Triple-Negative Breast Cancer (TNBC) treated with standard sequential anthracycline-containing regimens
Cohort B
Patients with stage II-III HER2-positive breast cancer receiving a non-anthracycline neoadjuvant regimen based on the TRAIN-2 strategy
Cohort C
Patients with stage II-III HER2-positive breast cancer treated according to a TRYPHAENA-like regimen
结局指标
主要结局
Longitudinal assessment of ctDNA clearance (yes/no) across the three study cohorts following the completion of the first neoadjuvant treatment block. Clearance milestones are tailored to specific regimens: pre-anthracycline exposure for Cohort A, after 6
时间窗: At the completion of neoadjuvant therapy Block 1 for each cohort (approximately 6 to 12 weeks from baseline, depending on the specific regimen schedule).
次要结局
未报告次要终点
研究者
Grazia Arpino
Professor
Federico II University