The Gut Microbiome and Immunotherapy Response in Solid Cancers
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Characterization of fecal microbiome using molecular methods
研究概览
简要总结
The aim of this study is characterize the gastrointestinal microbiomes of patient with solid cancer undergoing standard of care treatment with programmed cell death protein 1 (PD-1) /programmed cell death ligand (PD-L1) blockade.
详细描述
Frontline treatment for solid cancers such as renal cell carcinoma includes immunotherapies such as immune checkpoint inhibitor (ICI) therapy. Despite an increase in overall survival in cancer patients undergoing ICI therapy, many patients' tumors are unresponsive or eventually progress. Recent studies indicate that the gut microbiome composition is associated with clinical response to ICI treatment. Following the success of preclinical research, two recent studies investigated the efficacy of fecal microbiota transplant (FMT) from cancer patients responsive to programmed cell-death protein 1 (PD-1) blockade, a type of ICI treatment, to patients nonresponsive to treatment. Notably, 30-40% of the FMT recipients in these studies subsequently responded to anti-PD-1 therapy. However, the effectiveness of FMT may vary among donors, there is no clear agreement on the ideal FMT composition, and FMT carries the risk of transmitting infection. An alternative to FMT is identification of specific efficacious commensals for supplementation. While the specific commensals enriched in cancer patients with more favorable outcomes vary from study to study, several are commonly reported, including Akkermansia muciniphila, Bacteroides spp., Bifidobacterium spp., Ruminococcaceae spp., and Faecalibacterium spp.
Cancer-related fatigue is experienced by nearly all patients during treatment, and cancer-related cognitive impairment (CRCI), which is a decrease in neurocognitive functioning that can be caused by cancer or its treatment, is present in up to ¾ of patients during treatment. Fatigue and CRCI have both been linked to the composition of the gut microbiome in cancer patients.
Specific Aims
Specific Aim 1: Characterize the gut microbiome of solid cancer patients that have had disease progression during standard-of-care treatment with PD-1 or programmed cell death ligand 1 (PD-L1) blockade and compare to solid cancer patients that were stable or experienced tumor shrinkage during standard-of-care treatment with PD-1/PD-L1 blockade.
Specific Aim 2: Assess neuropsychological measures of cognition and fatigue in solid cancer patients undergoing standard-of-care treatment with PD-1/PD-L1 blockade and determine associations with composition of the gut microbiome.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Current diagnosis of malignant solid cancer that is nonresectable or metastatic.
- •Ages 35 to 75 years.
- •Treatment with immunotherapy, specifically programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor, for at least 3 months but less than 24 months (except for previously responsive subjects re-enrolling as non-responsive patients).
- •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.
- •Participant is willing and able to give informed consent for participation in the study
排除标准
- •Significant heart, liver, blood or respiratory disease.
- •Current diagnosis of HIV, Hepatitis B or Hepatitis C.
- •History of heart disease.
- •Uncontrolled diabetes mellitus.
- •Subjects with a history of inflammatory bowel disease, Celiac disease or active diverticular disease.
- •Females who are pregnant or lactating.
- •Treatment with chemotherapy within the past 2 years.
- •Treatment with kinase inhibitors within the past 3 months.
- •Previous radiation therapy for brain metastases.
- •Other medical condition or medication administration deemed exclusionary by the study investigators.
结局指标
主要结局
Characterization of fecal microbiome using molecular methods
时间窗: baseline
Characterization of the fecal microbiome using a commercially available sampling kit and our lab's patented array for PCR.
次要结局
- Cognitive Function as measured by Montreal Cognitive Assessment(baseline)
- Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale(baseline)
- Gastrointestinal Health measured by the Gastrointestinal Symptom Rating Scale(baseline)
- Fatigue as measured by the Multidimensional Fatigue Symptom Inventory(baseline)