Predicting Response to Immunotherapy for Melanoma With Gut Microbiome and Metabolomics
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 450
- 试验地点
- 5
- 主要终点
- Gut microbiome diversity via measurement of bacterial species in stool samples
研究概览
简要总结
This study will investigate the effects of gut microbiome diversity (richness in terms of many bacterial species in the gut) on responses and side effects of immunotherapy in advanced melanoma patients. Immunotherapy for melanoma is especially damaging for the gut with colitis which can lead to death and significant morbidity with repeated hospital admissions. The richness of the microbiome in the gut may be protective against colitis and other side effects but this needs to be confirmed. There is also some preliminary evidence that the gut microbiome diversity can enhance responses to immunotherapy in cancer but this has been shown in small numbers of melanoma patients.
详细描述
This pilot project will assess the gut microbiome with metagenome sequencing before and after starting immunotherapy in stage 3 and 4 melanoma patients. The project will assess the impact of the gut microbiome on treatment response rates and side effects induced by immunotherapy.
200 stage 4 and 250 stage 3 melanoma patients naive to immunotherapy will be recruited from melanoma clinics. Stool samples will be donated pre-treatment and at follow-up visits throughout treatment. An additional sample will also be requested in the event of disease progression or toxicity necessitating treatment delay or discontinuation. An accompanying stool sample questionnaire will be completed at each sampling time point with the optional completion of a 24-hour recall food diary.
Blood samples will also be taken before and after starting immunotherapy treatment, with gastrointestinal, food frequency, quality of life questionnaires administered at baseline. An optional tumour biopsy if safe and accessible, is requested from patients in the stage 4 cohort before and after starting immunotherapy.
Microbiome data from melanoma patients will be compared with the TwinsUK healthy control gut microbiome data on more than 3000 healthy adults. This analysis will help us assess if there are major differences between the microbiome composition in the melanoma cases prior to therapy compared to the control gut microbiome data from TwinsUK.
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
- •Patients aged over the age of 18 years with advanced melanoma due to receive first line systemic treatment with immunotherapy with a checkpoint inhibitor alone or in combination.
排除标准
- •Patients who have had systemic anti-cancer treatment for locally advanced or metastatic disease.
- •Patients unable to consent because of language barrier or inability to consent.
- •Patients unable to collect or send the stool samples for geographical, social or psychological reasons.
- •Persons benefitting from protection system of adults (including guardianship and curatorship)
- •Pregnant or breastfeeding women
结局指标
主要结局
Gut microbiome diversity via measurement of bacterial species in stool samples
时间窗: 3-5 years
Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in patients with stage 3 or stage 4 melanoma receiving immunotherapy
Peripheral blood monocyte measurements to determine the characterisation of peripheral blood mononuclear cells (immunophenotyping) and inflammatory markers before and after starting immunotherapy treatment.
时间窗: 3-5 years
Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in patients with stage 3 or stage 4 melanoma receiving immunotherapy.
Side effects as determined by CTCAE scale Common Toxicity Criteria for Adverse Events v5.03
时间窗: 3-5 years
Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in patients with stage 3 or stage 4 melanoma receiving immunotherapy.
次要结局
- Analysis of optional punch biopsy samples before and after commencing immunotherapy treatment in patients with stage 4 melanoma(3-5 years)