Determination of Microbiological Factors Associated With Poor Response to Neoadjuvant Therapy in Rectal Cancers: Focus on Cyclomodulin-producing Escherichia Coli
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 4
- 主要终点
- The ratio between the proportions of poor response to neoadjuvant treatment in populations so-called "exposed" (patients colonized by bacteria producing toxins (cyclomodulin) and unexposed (patients not colonized by bacteria producing toxins)
研究概览
简要总结
The objective of this project is to determine in a non-invasive manner (fecal samples) the predictive value of the intestinal microbiota and the presence of genotoxin-producing bacteria on the response to neoadjuvant treatment in rectal cancer. This could lead to a better understanding and selection of patients for personalized treatment in rectal cancer.
详细描述
Rectal cancer is the 8th leading cause of cancer in the world with more than 300,000 deaths in 2018. In addition to surgery, neoadjuvant treatment has proven its value in reducing local recurrences. Evaluation of the response to neoadjuvant treatment (essential for the subsequent therapeutic decision but also for the oncological prognosis. It is based on rectal magnetic resonance imaging, completed after surgery by anatomopathology. A personalised treatment with therapeutic de-escalation or intensification for aggressive tumours can be decided depending on the response to Neoadjuvant treatment. Thus, knowledge of the predictive factors of response to neoadjuvant treatment would permit to anticipate and adapt care.
The intestinal microbiota is a true microbial organ, playing a major role in maintaining intestinal homeostasis. Some bacterial species have been identified and suspected of playing a role in colorectal carcinogenesis. Among these species, genotoxin-producing Escherichia coli (CPEC) strains such as colibactin (cyclomodulin encoded by the genomic islet pks) are preferentially detected in patients with colorectal cancer (CRC), especially the most aggressive forms. Recent studies show that the intestinal microbiota is a prognostic factor in the response to certain chemotherapies or immunotherapies, but little work has been done on its potential influence on the effectiveness of radiotherapy. This suggests the possibility of using these biomarkers associated with response to neoadjuvant treatment.
The objective of this project is to determine in a non-invasive manner (fecal samples) the predictive value of the intestinal microbiota and the presence of genotoxin-producing bacteria on the response to neoadjuvant treatment in rectal cancer. This could lead to a better understanding and selection of patients for tailored treatment in rectal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Histologically proven lower and mid-rectal adenocarcinoma at clinical stage II and III
- •Patient is to receive neoadjuvant treatment (radiochemotherapy or chemotherapy or radiotherapy). Induction chemotherapy such as folfox or folfirinox is allowed
- •Patient who has signed the informed consent of the study
- •Male or female ≥ 18 years old
- •Appropriate contraceptive measures should be used by both men and non-menopausal women before entering the trial until at least 8 weeks after the last course of radiochemotherapy. The investigator should inform the patient about the contraceptive measures to be used.
排除标准
- •Antibiotic treatment at the time or in the month preceding stool sampling
- •Presence of an ostomy
- •Previous treatment for rectal cancer
- •Patient not affiliated to a French social protection system
- •Patient not in favour of good compliance with treatment for psychological, family, social or geographical reasons
- •Legal incapacity (Patient under curatorship or guardianship)
- •Prior radiation therapy or pelvic curia in the year prior to inclusion
- •History of other cancers in the last 5 years (except for in-situ cervical carcinomas and non-melanoma skin carcinomas treated optimally)
- •Pregnant or breastfeeding woman
结局指标
主要结局
The ratio between the proportions of poor response to neoadjuvant treatment in populations so-called "exposed" (patients colonized by bacteria producing toxins (cyclomodulin) and unexposed (patients not colonized by bacteria producing toxins)
时间窗: About 1 years
次要结局
- Change of cyclomodulin-Producing Escherichia Coli colonization rate before and after neoadjuvant treatment(About 1 years)
- Change of cyclomodulin-Producing Escherichia Coli prevalence before and after neoadjuvant treatment(About 1 years)
- Relative risk of poor response to neoadjuvant treatment in colonized patients with other bacteria ("exposed") compared to non-colonized patients ("unexposed")(About 1 years)
- Types of other bacteria forming the overall bacterial composition before neoadjuvant treatment(About 1 years)
- Change of prevalence forming the overall bacterial composition before and after neoadjuvant treatment(About 1 years)
- Change of colonization rate (in addition to cyclomodulin-Producing Escherichia Coli) forming the overall bacterial composition before and after neoadjuvant treatment(About 1 years)
- Proportion of patients colonized according to the modality of the clinical variable age(About 1 years)
- Proportion of patients colonized according to the modality of the clinical variable body mass index(About 1 years)
- Proportion of patients colonized according to the modality of the clinical variable gender(About 1 years)
- Disease-free survival in colonized people by the different types of bacteria that form the overall bacterial composition (including cyclomodulin-Producing Escherichia Coli) compared to non-colonized people(About 1 years)
- Overall survival in colonized people by the different types of bacteria that form the overall bacterial composition (including cyclomodulin-Producing Escherichia Coli) compared to non-colonized people(About 1 years)
- Specific survival in colonized people by the different types of bacteria that form the overall bacterial composition (including cyclomodulin-Producing Escherichia Coli) compared to non-colonized people(About 1 years)