Circulating Tumor DNA as a Predictor of Relapse in Patients With Locally Advanced Rectal Cancer Treated With Total Neoadjuvant Therapy Followed by Watch and Wait or Total Mesorectal Excision Based on Clinical Assessment of Response
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 120
- 试验地点
- 15
- 主要终点
- ctDNA from liquid biopsy
研究概览
简要总结
The evaluation of the tumor response to chemoradiotherapy/total neoadjuvant therapy (CRT/TNT) remains a challenge. The integration of a blood-based biomarker such as ctDNA with clinico-radiological tools could offer the potential advantage of improving accuracy of assessment of tumor response to neoadjuvant therapy. Furthermore, data on functional outcomes and quality of life after total mesorectal excision (TME) and especially after " Watch And Wait" (WW) is scarce.
REVEAL is a prospective, multicenter study in which the response to TNT in correlation with liquid biopsy (LB) of patients with rectal cancer in Spain will be evaluated. It is planned to include 120 patients. All patients will be aged 18 years or older, with histologically confirmed rectal adenocarcinoma, located in the mid or distal third (with the inferior margin within 12cm from the anal verge), clinically staged II and III (cT3-T4 and/or any TN+), scheduled to undergo TNT will be eligible. All cases and treatment decisions will be discussed by local Multidisciplinary Boards. Patients will be included consecutively when visiting the corresponding health centers for outpatient visits or hospitalization.
The objective of the present study is to evaluate the role of ctDNA in the prediction of relapse in patients diagnosed with locally advanced rectal cancer (LARC) treated with TNT followed by WW or TME based on a clinical assessment of the local response
详细描述
The evaluation of the tumor response to chemoradiotherapy/total neoadjuvant therapy (CRT/TNT) remains a challenge. The integration of a blood-based biomarker such as ctDNA with clinico-radiological tools could offer the potential advantage of improving accuracy of assessment of tumor response to neoadjuvant therapy. Furthermore, data on functional outcomes and quality of life after total mesorectal excision (TME) and especially after " Watch And Wait" (WW) is scarce.
REVEAL is a prospective, multicenter study in which the response to TNT in correlation with liquid biopsy (LB) of patients with rectal cancer in Spain will be evaluated. It is planned to include 120 patients. All patients will be aged 18 years or older, with histologically confirmed rectal adenocarcinoma, located in the mid or distal third (with the inferior margin within 12cm from the anal verge), clinically staged II and III (cT3-T4 and/or any TN+), scheduled to undergo TNT will be eligible. All cases and treatment decisions will be discussed by local Multidisciplinary Boards. Patients will be included consecutively when visiting the corresponding health centers for outpatient visits or hospitalization.
The objective of the present study is to evaluate the role of ctDNA in the prediction of relapse in patients diagnosed with locally advanced rectal cancer (LARC) treated with TNT followed by WW or TME based on a clinical assessment of the local response.
HYPOTHESIS ctDNA is a predictor of complete clinical response and could potentially be used to guide patient selection for WW strategy.
ctDNA is an early marker of local tumor relapse and could potentially guide strategy changes during follow-up.
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
- •Legally capable patients ≥ 18 years of age.
- •Histologically confirmed rectal adenocarcinoma.
- •Any tumor located in the mid or distal rectum, clinically staged II-III (cT3/4 and/or any TN+).
- •Willingness to be enrolled in the WW strategy if cCR or nCCR is achieved.
- •Absence of metastases on imaging.
- •Scheduled to undergo TNT followed by delayed surgery.
- •Patients who have signed the informed consent for this study.
- •Note: Decision was taken to treat the patient with a specific treatment prior and independently of patient inclusion in this non interventional study.
排除标准
- •Patients who do not meet inclusion criteria.
- •Concomitant colorectal tumors.
- •Intolerance or contraindication to planned TNT.
- •Other concurrent malignant diseases. Pregnancy or breastfeeding.
结局指标
主要结局
ctDNA from liquid biopsy
时间窗: 2 years after to start treatment total neoadjuvant therapy/2 years per patient
The results from ctDNA will be dichotomized to positive or negative. The investigator will report the percentage of patients with positive or negative ctDNA. Correlation of these values with clinical endpoints of response / survival to total neoadjuvant therapy will be done to fulfill the proposed objectives of this study. The ctDNA isolation test selected for this study is marketed by Guardant Health (Redwood City, California, USA) under the name Guardant RevealTM. It consists of a single state-of-the-art liquid blood biopsy, which is capable of detecting residual or recurrent disease seven days after blood extraction. This test uses a sequencing method that simultaneously evaluates genetic alterations and methylation without the need for a biopsy of the primary tumor tissue to determine specific mutations.
次要结局
- Disease-specific Survival (DSS)(at 1 year after the first dose of TNT)
- TNT compliance(Throughout the study period, approximately 2 years per patient)
- Response to TNT (cCR,nCCR)(Throughout the study period, approximately 2 years per patient)
- Response to TNT (WW or TME)(Throughout the study period, approximately 2 years per patient)
- Locoregional failure rate (LRF)(Throughout the study period, approximately 2 years per patient)
- Distant relapse rate (DRR)(Throughout the study period, approximately 2 years per patient)
- Overall Survival (OS)(at 1 year after the first dose of TNT)
- Disease-free Survival (DFS)(at 1 year after the first dose of TNT and at the end of study (approximately 2 years))
- Mortality(Throughout the study period, approximately 2 years per patient)