Evaluation of Circulating Tumor DNA Based Minimal Residual Disease Detection in Early Stage Breast Cancer Patients: A Prospective Study
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 入组人数
- 350
- 试验地点
- 5
- 主要终点
- Proportion of patients that achieve a pathologic complete response and are circulating tumor deoxyribonucleic acid (ctDNA) detectable (Cohort 1)
研究概览
简要总结
This clinical trial studies how well circulating tumor deoxyribonucleic acid (ctDNA) based minimal residual disease (MRD) detection works for patients with early-stage breast cancer. MRD refers to a very small number of tumor cells that remain in the body during or after treatment. ctDNA refers to small pieces of DNA that are released into a person's blood by tumor cells as they die. Management of patients after cancer surgery remains a clinical dilemma, particularly for cancer detected at earlier stages as many patients are cured by surgery alone. This results in very large clinical trials required to demonstrate a modest benefit from treatment. Using ctDNA MRD testing in early-stage breast cancer patients receiving standard treatment may help researchers identify groups that would benefit from additional therapy, leading to better outcomes.
详细描述
PRIMARY OBJECTIVES:
I. To determine the pathologic response rate and presence of ctDNA post-neoadjuvant therapy in stage I-III breast cancer patients receiving neoadjuvant systemic therapy followed by curative-intent surgical resection, separately for Subgroup 1A: human epidermal growth factor receptor 2 positive (HER2+) (any estrogen receptor [ER]/progesterone receptor [PR] status) and Subgroup 1B: triple negative breast cancer (TNBC). (Cohort 1) II. To determine ctDNA detectability before and after curative-intent surgical resection in Cohort 2 ER+/any progesterone receptor (PR)/HER2- stage I-III breast cancer patients. (Cohort 2)
SECONDARY OBJECTIVES:
I. To determine ctDNA detectability before and after adjuvant chemotherapy and/or radiation therapy, by cohort and subgroup.
II. To determine ctDNA detectability during the follow-up period of up to 3 years after definitive treatment, by cohort and subgroup.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- None
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
- •Documented written informed consent of the participant
- •Age ≥ 18 years
- •Diagnosis of stage I-III breast cancer (any gender)
- •Malignancy must be epithelial. Non-epithelial breast malignancies such as lymphoma or sarcoma are not allowed
- •Willingness to:
- •Provide blood samples
- •Provide archival tumor tissue sample (only necessary for Cohort 2 if analysis of surgical tissue was not successful)
- •Provide tumor tissue sample from resection/surgery (only necessary for Cohort 1 if analysis of surgical tissue was not successful)
- •Permit medical record review
- •Fall into one of the following categories defined below: Cohort 1, Subgroup A or B OR Cohort 2
- •COHORT 1: Must have archival diagnostic tissue available
- •COHORT 1: Scheduled to undergo, but has not yet begun, neoadjuvant systemic therapy followed by curative resection
- •COHORT 1 (Subgroup A): HER2+ by current American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guidelines (any ER/PR status)
- •COHORT 1 (Subgroup B): Triple negative (ER, PR and HER2 negative). Defined as ER and PR ≤ 10% by immunohistochemistry (IHC) and HER2 negative, by current ASCO/CAP guidelines
- •COHORT 2: Scheduled to undergo upfront curative surgical resection with or without adjuvant chemotherapy followed by adjuvant endocrine therapy
- •COHORT 2: ER+/any PR/HER2- (ER positive defined as ER > 10% by IHC)
排除标准
- •Ductal carcinoma in situ
- •Inability to safely provide sequential blood samples
- •Prior or concurrent invasive malignancy (unless disease free > 5 years)
- •An employee who is under the direct/ indirect supervision of the principal investigator (PI)/ a co-investigator/ the study manager
- •A direct study team member
- •Inability to give informed consent
研究组 & 干预措施
Cohort 1 (blood collection for ctDNA testing - 1)
Patients undergo collection of blood samples for ctDNA testing at 14-21 days post cycle 1, day 1 of SOC neoadjuvant chemotherapy, on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.
干预措施: Biospecimen Collection (Procedure)
Cohort 1 (blood collection for ctDNA testing - 1)
Patients undergo collection of blood samples for ctDNA testing at 14-21 days post cycle 1, day 1 of SOC neoadjuvant chemotherapy, on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.
干预措施: Electronic Health Record Review (Other)
Cohort 1 (blood collection for ctDNA testing - 1)
Patients undergo collection of blood samples for ctDNA testing at 14-21 days post cycle 1, day 1 of SOC neoadjuvant chemotherapy, on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.
干预措施: Survey Administration (Other)
Cohort 2 (blood collection for ctDNA testing -2)
Patients undergo collection of blood samples for ctDNA testing on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.
干预措施: Biospecimen Collection (Procedure)
Cohort 2 (blood collection for ctDNA testing -2)
Patients undergo collection of blood samples for ctDNA testing on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.
干预措施: Electronic Health Record Review (Other)
Cohort 2 (blood collection for ctDNA testing -2)
Patients undergo collection of blood samples for ctDNA testing on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.
干预措施: Survey Administration (Other)
结局指标
主要结局
Proportion of patients that achieve a pathologic complete response and are circulating tumor deoxyribonucleic acid (ctDNA) detectable (Cohort 1)
时间窗: Up to 3 years after standard of care (SOC) surgery
Baseline characteristics will be compared using the K-sample equality-of-medians test with continuity correction and the two-sample test of proportions. Cox proportional-hazards models, with the exact partial likelihood method to handle tied event times and adjusting for post-baseline ctDNA (negative versus positive), baseline tumor marker (not elevated versus elevated), and tumor stage as pre-specified confounders. Other confounders will be adjusted for as appropriate.
ctDNA detection rate (Cohort 2)
时间窗: Before and after SOC surgery (up to 3 years)
Baseline characteristics will be compared using the K-sample equality-of-medians test with continuity correction and the two-sample test of proportions. Cox proportional-hazards models, with the exact partial likelihood method to handle tied event times and adjusting for post-baseline ctDNA (negative versus positive), baseline tumor marker (not elevated versus elevated), and tumor stage as pre-specified confounders. Other confounders will be adjusted for as appropriate.
次要结局
- ctDNA detection rate 1(Before and after adjuvant chemotherapy and/or radiation therapy (up to 3 years))
- ctDNA detection rate 2(Up to 3 years post-definitive treatment)
- Recurrence free survival (RFS)(Post-neoadjuvant treatment and post-surgery (up to 3 years))
- ctDNA level(Up to 3 years after SOC surgery)
- Rate of concordance between ctDNA changes on systemic treatment and clinical response(Up to 3 years after SOC surgery)
- Difference in time between ctDNA detection date and radiographic disease progression date(Up to 3 years after SOC surgery)