Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Feasibility of evaluating intestinal microbiome composition and autoimmune panels in patients treated with immunooncology combinations through the analysis of stool and blood samples at multiple time-points.
研究概览
简要总结
This is a single-center, investigator-initiated, non-interventional study evaluating the role of the intestinal microbiome and autoimmune panels as a predictor for developing ≥ Grade 2 CTCAE v5.0 immune-related adverse event (irAE) and/or requiring systemic immunosuppression for irAEs in advanced solid tumor patients receiving immunooncology (IO) combinations at the Princess Margaret Cancer Centre. This is a minimal risk study involving the analysis of patient samples and does not involve therapeutic intervention.
The study will involve a prospective cohort of up to 120 patients and it is anticipated that patient accrual will be completed within 18 months.
Patients will receive IO combination as per their specific protocols from their other clinical trial or per their standard of care and samples will be collected at multiple time-points. No additional visits to the hospital will be needed for this study as safety assessments are already captured for all patients based on their participation in a clinical trial or per their standard of care.
详细描述
Accumulating evidence supports that differential composition of fecal microbiome influences response to immunotherapy and development of colitis. Microbiome with different profiles are also associated with multiple diseases, including gastrointestinal (GI) or non-GI auto-immune pathologies. Little is known about the relationship between the microbiome composition or fecal calprotectin (fCal) and the development of non-colitis immune-related adverse events (irAEs) during treatment with IO combinations.
Autoimmune conditions and irAEs from immune checkpoint inhibitors (ICI) drugs both involve loss of tolerance to endogenous antigens and produce similar clinical presentations. ICI can increase humoral response. However, to date there is no evidence that autoimmune panels are correlated with the development of irAEs during IO combination therapy.
These findings suggest that analyzing the microbiome and autoimmune panels of patients treated with IO combinations at multiple time-points may be feasible. In addition, baseline, early shift and changes in microbiome and autoimmune panels at time of a serious irAE may be correlated with the development of serious irAEs and may change with appropriate immunosuppressive regimens.
We hypothesize that analysing the microbiome and autoimmune panels of patients treated with immunooncology (IO) combinations at multiple time-points is feasible. Additionally, we hypothesize that baseline, early shift and changes in microbiome and autoimmune panels at time of a serious immune-related adverse event (irAE) is correlated with the development of serious irAEs and will change with appropriate immunosuppressive regimens.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 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
- •Signed written and voluntary informed consent.
- •Patient must be willing and able to provide collection for blood and stool specimen analysis at the pre-specified time-points.
- •Age > 18 years, male or female.
- •Patient must be diagnosed with any advanced solid tumor deemed incurable and to be treated at Princess Margaret Cancer Centre.
- •Patients must be eligible to treatment with an IO combination.
排除标准
- •Any conditions that in the opinion of the Investigator would interfere with patient safety, or evaluation of the collected specimen and interpretation of study result.
- •History of autoimmune disease with a flare episode within one year before study screening.
结局指标
主要结局
Feasibility of evaluating intestinal microbiome composition and autoimmune panels in patients treated with immunooncology combinations through the analysis of stool and blood samples at multiple time-points.
时间窗: 18 months
To assess the feasibility, the endpoint will be deemed feasible if \>50% of patients have biospecimens collected in at least 2 time-points.
次要结局
- Correlation between baseline autoimmune panels to the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.(18 month)
- Correlation between the early changes in fecal calprotectin levels to the development of ≥ Grade 2 CTCAE v5.0 colitis and/or requiring systemic immunosuppression for colitis.(18 months)
- Evaluate intestinal microbiome, autoimmune panel reactivity & fCal changes from baseline to development of ≥ Gr2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs, & from event diagnosis to resolution to ≤ Gr1 CTCAE v5.0 irAEs(18 months)
- Correlation between baseline intestinal microbiome composition to the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.(18 months)
- Correlation between baseline fecal calprotectin levels to the development of ≥ Grade 2 CTCAE v5.0 colitis and/or requiring systemic immunosuppression for colitis.(18 months)
- Correlation between the early changes in composition of intestinal microbiome and the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.(18 months)
- Correlation between the early changes in composition of autoimmune panels and the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.(18 months)