Safety and Feasibility of Akkermansia Probiotics Combined With Anti-PD-1 Monoclonal Antibody in MSS/pMMR Advanced Colorectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
The investigators propose to conduct a single-center, single-arm, Phase I clinical study to explore the safety and feasibility of Akkermansia probiotics combined with anti-PD-1 monoclonal antibody in patients with MSS/pMMR advanced colorectal cancer, as well as its impact on gut microbiota and the immune microenvironment.
详细描述
Safety and Feasibility of Akkermansia Probiotics Combined with Anti-PD-1 Monoclonal Antibody in MSS/pMMR Advanced Colorectal Cancer The investigators propose to conduct a single-center, single-arm, Phase I clinical study to explore the safety and efficacy of Akkermansia probiotics combined with anti-PD-1 monoclonal antibody in patients with MSS/pMMR advanced colorectal cancer, as well as its impact on gut microbiota and the immune microenvironment.
Inclusion Criteria:
- Age 18-75 years
- ECOG performance status score of 0-2
- Histopathologically confirmed colorectal cancer; tumor tissue immunohistochemistry or genetic testing showing pMMR or MSS/MSI-L type
- Metastatic colorectal adenocarcinoma that has failed standard treatments (including irinotecan, oxaliplatin, fluorouracil, bevacizumab, cetuximab, etc.)
- No prior use of immunotherapy (such as immune checkpoint inhibitors, adoptive cell immunotherapy, etc.)
- At least one evaluable lesion according to RECIST version 1.1 criteria
- No intestinal obstruction and good oral compliance
- Adequate bone marrow, liver, and kidney function to receive treatment
- Signed informed consent
Exclusion Criteria:
- History of allergic diseases, severe drug allergies, or known allergies to probiotic drugs
- Use of antibiotics or probiotic drugs/health products within the last 3 months
- History of other malignancies with a disease-free interval of less than 5 years (except for cured basal cell carcinoma of the skin, cured cervical carcinoma in situ, and gastrointestinal tumors cured by endoscopic mucosal resection)
- Presence of any active autoimmune disease or history of autoimmune disease
- Current use of immunosuppressants or hormone therapy, continued within 2 weeks prior to enrollment
- Concurrent severe infections
- Congenital or acquired immune deficiency, or active hepatitis
- Concurrent severe complications
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Age 18-75 years
- •ECOG performance status score of 0-2
- •Histopathologically confirmed colorectal cancer; tumor tissue immunohistochemistry or genetic testing showing pMMR or MSS/MSI-L type
- •Metastatic colorectal adenocarcinoma that has failed standard treatments (including irinotecan, oxaliplatin, fluorouracil, bevacizumab, cetuximab, etc.)
- •No prior use of immunotherapy (such as immune checkpoint inhibitors, adoptive cell immunotherapy, etc.)
- •At least one evaluable lesion according to RECIST version 1.1 criteria
- •No intestinal obstruction and good oral compliance
- •Adequate bone marrow, liver, and kidney function to receive treatment
- •Signed informed consent
排除标准
- •• History of allergic diseases, severe drug allergies, or known allergies to probiotic drugs
- •Use of antibiotics or probiotic drugs/health products within the last 3 months
- •History of other malignancies with a disease-free interval of less than 5 years (except for cured basal cell carcinoma of the skin, cured cervical carcinoma in situ, and gastrointestinal tumors cured by endoscopic mucosal resection)
- •Presence of any active autoimmune disease or history of autoimmune disease
- •Current use of immunosuppressants or hormone therapy, continued within 2 weeks prior to enrollment
- •Concurrent severe infections
- •Congenital or acquired immune deficiency, or active hepatitis
- •Concurrent severe complications
研究组 & 干预措施
Self control group
According to the inclusion and exclusion criteria, 22 patients will be recruited. After enrollment, patients will receive anti-PD-1 monoclonal antibody + Tyrosine kinase inhibitor (TKI, e.g., regorafenib, fruquintinib) treatment or anti-PD-1 monoclonal antibody ± chemotherapy (etc., CAPEOX [oxaliplatin+capecitabine ], XELIRI [irinotecan+capecitabine ]) ± Bevacizumab treatment (anti-PD-1 monoclonal antibody, chemotherapy, and bevacizumab every 3 weeks, TKI every 4 weeks), along with daily continuous administration of Akkermansia probiotics (Songke, dose: 1 capsule/day, taken with breakfast), until disease progression, intolerable toxicity, or patient withdrawal from the study.
干预措施: Akkermansia Probiotics (Dietary Supplement)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: From enrollment to one months after study exit
Physical Symptoms (Nausea, vomiting, headache, dizziness, fatigue, rash, itching, pain, etc); Laboratory Abnormalities: (Abnormal blood test results); Clinical Signs (ever, swelling, high blood pressure, low blood pressure, rapid heart rate, etc); Worsening of Pre-existing Conditions (xacerbation of a pre-existing disease or medical condition); New Medical Conditions (Development of new diseases or disorders that were not present before treatment); Psychological Effects (Anxiety, depression, insomnia, confusion, etc).
次要结局
- Objective Response Rate (ORR)(Up to 12 months)
- Relative abundance of Akkermansia muciniphila (AKK) in fecal samples measured by qPCR(Through study completion, an average of 2 months)
- Quantitative analysis of peripheral blood immune cell subsets (CD8+ T cells, DC subtypes, MDSCs,, etc.) by flow cytometr(Through study completion, an average of 2 months)
- Serum cytokine profiling (IFN-γ, TNF-α, etc.) by ELISA(Through study completion, an average of 2 months)
- Changes in gut microbiome composition measured by 16S rRNA gene sequencing analysis(Through study completion, an average of 2 months)
- Progression-Free Survival (PFS)(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- Overall Survival (OS)(Up to 36 months)
- Overall Survival (OS)(Up to 36 months)
- Objective Response Rate (ORR)(Up to 12 months)
- Relative abundance of Akkermansia muciniphila (AKK) in fecal samples measured by qPCR(Through study completion, an average of 2 months)
- Quantitative analysis of peripheral blood immune cell subsets (CD8+ T cells, DC subtypes, MDSCs,, etc.) by flow cytometr(Through study completion, an average of 2 months)
- Serum cytokine profiling (IFN-γ, TNF-α, etc.) by ELISA(Through study completion, an average of 2 months)
- Progression-Free Survival (PFS)(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
研究者
Meng Qiu
Principal Investigator
West China Hospital