Probiotics Preventing Immune Checkpoint Inhibitor-Induced Colitis
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 发起方
- Mayo Clinic
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Incidence of immune checkpoint inhibitors (ICI)-induced colitis (IIC) with VSL#3 and ICIs
研究概览
简要总结
The clinical trial tests the use of over-the-counter probiotics VSL#3® 450B in patients receiving immunotherapy. Immunotherapy with monoclonal antibodies, helps the body's immune system attack tumor cells, and interferes with the ability of tumor cells to grow and spread. Immunotherapy can also cause an unfortunate side effect of inflammation of the colon and diarrhea, also known as immune checkpoint inhibitor induced colitis. Immune checkpoint inhibitor induced colitis can occur in up to 45% of patients receiving immunotherapy. Taking probiotics VSL#3® 450B may reduce the chances of developing immune checkpoint inhibitor induced colitis in patients receiving immunotherapy.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the incidence of immune checkpoint inhibitors (ICI)-induced colitis (IIC) in patients with solid malignancies receiving over-the-counter multi-strain probiotic blend and ICIs in both cohorts: (1) anti-Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) +/- anti-programmed cell death-1 (PD-1)/programmed cell death-1 ligand 1 (PD-L1), and (2) anti-PD-1/PD-L1 +/- chemo.
SECONDARY OBJECTIVES:
I. To evaluate the safety of multi-strain probiotic blend in cancer patients receiving ICIs.
II. To evaluate the clinical outcomes related to IIC, including the incidence of IIC, hospitalization, treatment delays, and administration of immunosuppressants.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Histologically confirmed solid malignancy
- •Will be starting on ICIs or have started ≤ 2 cycles of ICIs
- •For cohort 1: Ipilimumab with or without anti-PD-1/PD-L1 including but not limited to pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, or durvalumab
- •For cohort 2: Anti-PD-1/PD-L1 described above with or without chemotherapy
- •Absolute neutrophil count (ANC) ≥ 1000/mm^3
- •Platelet count ≥ 75,000/mm^3
- •Hemoglobin ≥ 9.0 g/dL
- •Creatinine ≤ 2 x upper limit of normal (ULN)
- •Serum glutamic-oxaloacetic transaminase (SGOT) [aspartate transaminase (AST)] ≤ 2 x ULN
- •Albumin ≥ 3 g/dL
- •Willing and able to provide research stool and blood samples
- •Negative serum pregnancy test done ≤ 7 days prior to enrollment, for women of childbearing potential only
- •Capable of providing valid informed consent
- •Willing to return to enrolling institution for all study visits (blood draws, etc)
排除标准
- •Requires prolonged systemic antibiotic therapy for other condition and recent systemic antibiotic within the past 2 weeks
- •Fecal microbiota transplant (FMT) within the past 6 months
- •FMT with an associated serious adverse event related to the FMT product or procedure
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of over-the-counter probiotics
- •Immunocompromised patients including patients known to be HIV positive or those on chronic steroids > 20 mg prednisone a day or prednisone-equivalent Note: Must be off systemic steroids at least 90 days prior to enrollment. However, topical steroids, inhalants or steroid eye drops are permitted
- •History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis
- •History of chronic diarrhea
- •History of celiac disease
- •Currently has a colostomy
- •Intraabdominal surgery related to gastrointestinal tract within the last 60 days
- •Evidence of active, severe colitis
- •History of short gut syndrome or motility disorders
- •Requires the regular use of medications to manage bowel hypermotility
- •Active autoimmune disease that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to randomization. Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded
结局指标
主要结局
Incidence of immune checkpoint inhibitors (ICI)-induced colitis (IIC) with VSL#3 and ICIs
时间窗: Up to 14 weeks
Will be evaluated in patients with solid malignancies in 2 cohorts, including 1) anti-CTLA4 ± anti-PD-1/PD-L1, 2) anti-PD-1/PD-L1 ± chemotherapy respectively. Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Will be estimated by the number of patients who had IIC divided by the total number of evaluable patients. Two-sided 90% exact confidence intervals for the true incidence rate will be calculated according to the approach of Clopper and Pearson.
次要结局
- Incidence of treatment delays related to IIC(Up to 14 weeks)
- Incidence of adverse events(Up to 30 days post treatment)
- Incidence of hospitalization related to IIC(Up to 14 weeks)
- Incidence of administration of immunosuppressants related to IIC(Up to 14 weeks)