Fecal Microbiota Transplantation to Treat Diarrhea Induced by Tyrosine-kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma: a Randomized Clinical Trial.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments
研究概览
简要总结
Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with metastatic renal cell carcinoma, and are commonly used as first-line option for this condition, but their use is encumbered by side effects, mainly diarrhea, for which there are no standardized strategies. Increasing evidence suggests that gut microbiota could influence the development of TKIs-induced diarrhea. In theory, the therapeutic modulation of gut microbiota could be an approach to alleviate TKI-induced diarrhea. Fecal microbiota transplantation (FMT) is the infusion of fecal microbiota from a healthy donor in the gut of a recipient with the aim of curing a specific disease. It has been increasingly recognized as a highly effective treatment against recurrent Clostridium difficile infection.To date, the effects of FMT on chemotherapy-related diarrhea are unknown. This study will evaluate, through a randomized controlled design, the efficacy of fecal microbiota transplantation (FMT), compared with sham FMT, in treating TKI-induced diarrhea in patients with metastatic renal cell carcinoma.
详细描述
Despite the improvement in diagnosis and management, renal cell carcinoma (RCC) remains one of the most burdensome urological cancers, being the sixth most common malignancy in men and the 10th in women, accounting, respectively, for 5% and 3% of all cancers. Moreover, the incidence of RCC is increasing, especially in Western countries, accounting for nearly 60000 new cases per year in the United States. A considerable proportion of patients present with metastatic disease at diagnosis, and there are more than 140000 RCC-dependent deaths per year worldwide according to the World Health Organization.
Sunitinib and pazopanib are oral multi-targeted receptor tyrosine kinase inhibitors (TKIs) that have dramatically improved the survival of patients with metastatic RCC, and are commonly used as first-line option for this condition.
However, long-term use of these drugs is prevented by the development of toxicity. Diarrhea is one of the most common side effects of TKIs, occurring in nearly 50% of patients. It decreases the quality of life of these patients, and often requires dose reduction and drug discontinuation, potentially decreasing the efficacy of TKIs.
To date there are no standardized strategies for TKIs-related diarrhea, and current recommendations are supported by few evidence or real-life experience. Recommended treatment options include anti-motility agents, which are not targeted to act on the pathogenic pathways of diarrhea.
Increasing evidence suggests that gut microbiota could influence the development of TKIs-induced diarrhea. Overall, chemotherapy is known to drive, through the development of mucositis, deep compositional and functional alterations of gut microbiota. Mucositis occurs commonly after treatment with TKIs, and a specific dysbiotic profile has been found in patients with TKIs-induced diarrhea.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
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
- •18 years old or older
- •treatment with pazopanib or sunitinib for metastatic RCC diagnosed at histology and measurable according to RECIST criteria version 1.1
- •development of diarrhea of 2-3 grade according to Common Terminology Criteria (CTC) for Adverse Events (AE) version 4.0 induced by these drugs.
- •execution of a CT scan no earlier than 4 weeks before enrollment
- •good or intermediate prognostic assessment (according to criteria of the prognostic system of the International Metastatic RCC Database Consortium)
- •performance status equal or lower than 2
- •blood count, hepatic and kidney testing within normal limit
- •ability to give their consent to be included in the study.
- •Exclusion criteria:
- •another known cause of diarrhea (e.g. infectious gastroenteritis. Clostridium difficile infection, celiac disease, inflammatory bowel disease, irritable bowel syndrome, chronic pancreatitis, biliary salt diarrhea)
- •previous colorectal surgery or cutaneous stoma
- •food allergies
- •recent (<6 weeks) therapy with drugs that could possibly alter gut microbiota (e.g. antibiotics, probiotics, proton pump inhibitors, immunosuppressants, metformin)
- •another cancer (except for surgically treated basocellular carcinoma)
- •brain metastases
- •decompensated heart failure or heart disease with ejection fraction lower than 30%
- •severe respiratory insufficiency
- •psychiatric disorders
- •pregnancy
- •unable to give informed consent.
排除标准
- 未提供
结局指标
主要结局
rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments
时间窗: 4 weeks
rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments
次要结局
- rate of patients who experience resolution of diarrhea 1 week after the end of treatments(1 week)
- rate of patients who experience resolution of diarrhea 2 weeks after the end of treatments(2 weeks)
- rate of patients who experience resolution of diarrhea 8 weeks after the end of treatments(8 weeks)
- rate of patients who experience decrease of diarrhea until grade G1 or lower 1 week after the end of treatments(1 week)
- rate of patients who experience decrease of diarrhea until grade G1 or lower 2 weeks after the end of treatments(2 weeks)
- rate of patients who experience decrease of diarrhea until grade G1 or lower 4 weeks after the end of treatments(4 weeks)
- rate of patients who experience decrease of diarrhea until grade G1 or lower 8 weeks after the end of treatments(8 weeks)
- rate of patients who need to stop or reduce treatment with tyrosine-kinase inhibitors(4 weeks)
研究者
Giovanni Cammarota
Professor
Catholic University of the Sacred Heart