Study of the Predictive and Prognostic Role of Pharmacogenetic and Radiogenic Variants on the Response to Neoadjuvant Chemoradiation Therapy in Patients With Locally Advanced Rectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 460
- 试验地点
- 1
- 主要终点
- Defining the predictive role of rare (MAF<1%) and very rare genetic variants (MAF<0.1%) in the SMAD3 and IL-17F genes, implicated in nCRT-mediated activation of the immune system on the pathological tumour response to nCRT in LARC.
研究概览
简要总结
In locally advanced rectal cancer the pathological complete response (pCR) to neoadjuvant chemoradiation therapy (nCRT) is associated with a favourable long-term prognosis. The identification of markers predictive of response to therapy would therefore optimise treatment by allowing personalised therapy. It has been shown that the genetic profile of the patient could influence the activation of the immune system in combination with chemoradiation therapy in targeting tumour cells. In addition, genetic features of molecular pathways correlated with response to chemoradiotherapy, may in turn affect the probability of a good response to treatment in these patients, but also the occurrence of adverse events. The main objective of the study is to define the role of genetic markers related to immune system activation and other molecular pathways in predicting the complete pathological response to preoperative chemoradiation therapy in patients with locally advanced rectal cancer.
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
- 未提供
排除标准
- •evidence of secondary tumour
- •inadequate liver function (bilirubin >1.5 times the normal range, ALT and AST >2 times the normal range);
- •inadequate renal function (creatinine >1.5 times the upper limit of normal range);
- •Major concomitant systemic diseases that contraindicate surgery;
- •significant cardiovascular disease (heart failure, acute myocardial infarction within the last year, active angina, cardiac arrhythmia to be treated, uncontrolled hypertension)
- •systemic disease contraindicating radiotherapy
结局指标
主要结局
Defining the predictive role of rare (MAF<1%) and very rare genetic variants (MAF<0.1%) in the SMAD3 and IL-17F genes, implicated in nCRT-mediated activation of the immune system on the pathological tumour response to nCRT in LARC.
时间窗: up to 5 years
Relation between rare and very rare genetic variants and pathological tumour response will be assessed with logistic regression analysis and data will be reported as odds ratio and relative confidence interval
次要结局
- Plasma levels of IL-17F and SMAD3 proteins during treatment to be correlated with the genetic characteristics(up to 5 years)
- Plasma levels of IL-17F and SMAD3 proteins during treatment and tumour response(up to 5 years)
- Plasma levels of IL-17F and SMAD3 proteins during treatment and prognosis of the tumour.(up to 5 years)
- Identify further genetic markers of pathological tumour response(up to 5 years)
- Define the role of the same genetic polymorphisms on disease-free survival(up to 5 years)
- Define the role of the same genetic polymorphisms on overall survival of patients(up to 5 years)
- Define the role of the same genetic polymorphisms on the risk of developing severe treatment toxicities(up to 5 years)