Role of Microbiome in the Realm of Immune-Checkpoint Inhibitor Induced GI Complications In Cancer Population
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 800
- 试验地点
- 1
- 主要终点
- Difference in stool microbiome pattern
研究概览
简要总结
This trial studies the role of the gut microbiome and effectiveness of a fecal transplant on medication-induced gastrointestinal (GI) complications in patients with melanoma or genitourinary cancer. The gut microbiome (the bacteria and microorganisms that live in the digestive system) may affect whether or not someone develops colitis (inflammation of the intestines) during cancer treatment with immune-checkpoint inhibitor drugs. Studying samples of stool, blood, and tissue from patients with melanoma or genitourinary cancer may help doctors learn more about the effects of treatment on cells, and help doctors understand how well patients respond to treatment. Treatment with fecal transplantation may help to improve diarrhea and colitis symptoms.
详细描述
PRIMARY OBJECTIVES:
I. To compare the difference in stool microbiome pattern between patients who develop immune-checkpoint inhibitor (ICPI)-related colitis and patients who don't develop ICPI-related colitis.
II. To compare the difference in stool microbiome pattern in patients who developed ICPI-related colitis before and after colitis medical treatment.
III. To assess the safety and tolerability and efficacy of fecal microbiota transplantation (FMT).
SECONDARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 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
- •Diagnosis of any stage melanoma, Non-Small Cell Lung Cancer or genitourinary (GU) malignancies (Project 1).
- •Diagnosis of any cancer type (Projects 2 and 3)
- •Treatment with any ICPI agent
- •Ability to understand and willingness to sign an informed consent form and rate surveys
- •Life expectancy > 4 months (Project 3)
- •ICPI-related diarrhea and/or colitis of any grade with or without concurrent non- GI toxicity as the toxicity group (project 1)
- •Patients with no organ toxicity as the control group (project 1)
- •ICPI-related colitis and/or diarrhea of grade ≥ 2 as GI toxicity (initial episode or recurrence) receiving standard treatment of immunosuppressive agents (steroid, infliximab, vedolizumab, or ustekinumab) any time during the colitis disease course until sustained resolution of GI toxicity, or one- year time point after enrollment (Project 2)
- •ICPI-related colitis and/or diarrhea of grade ≥ 2 as GI toxicity without involvement of non- GI toxicity within 45 days prior to FMT (Project 3)
- •ICPI-related colitis and/or diarrhea of grade ≥ 2 within 45 days prior to FMT with ANY of the following characteristics (project 3):
- •(i) refractory to treatment of steroid and two doses of non-steroidal immunosuppressants e.g. infliximab, vedolizumab or ustekinumab,
- •(ii) contraindication for immunosuppressive treatment,
- •(iii) recurrence after successful initial treatment,
- •(iv) recurrent symptoms once steroid is tapered down/off or diarrhea/colitis symptoms are steroid dependent, or
- •(v) patients with a history of refractory ICPI-related colitis and/or diarrhea to medical treatment, even if they have improved symptoms from supportive care within 45 days prior to FMT
- •No concern for active concomitant GI infection for the ICPI diarrhea/colitis work up at the time of protocol therapy initiation as confirmed by stool tests or as per the treating physician based on clinical presentation (project 3)
- •Patient who has been cleared for enrollment by Infectious Diseases consultant or treating physician if positive infection workup or screening tests (e.g. lifelong positive T-spot due to BCG inoculation, chronic colonization) prior to initiation of diarrhea/colitis treatment (project 3)
排除标准
- •Age younger than 18 years
- •History of inflammatory bowel disease, and/or radiation enteritis or colitis with active disease status at the time of study treatment initiation
- •Pregnant and breastfeeding women
- •Women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test unless last menstrual cycle was > 1 year prior to consent and/ or clear documentation states that patient is peri- or post-menopausal or there was recent supporting objective evidence of 'no pregnancy' status (e.g. blood or imaging) within 30 days prior to date of study treatment
- •Patients who develop concurrent non- GI toxicity at the time of FMT treatment (project 3)
- •Patients with active bacterial or fungal infection (Project 3)
- •Donors at risk for monkeypox infection and/ or exposure as determined by a questionnaire (Project 3)
- •Withdrawal Criteria
- •Patients may withdraw from the trial at any time
- •Patients who develop GI perforation or toxic colitis that require surgery from ICPI colitis
- •In project 3, if the first 30% of cases fail the fecal transplant treatment, then project 3 will be terminated
研究组 & 干预措施
Supportive Care (standard of care, sample collection, FMT)
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
干预措施: Best Practice (Other)
Supportive Care (standard of care, sample collection, FMT)
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
干预措施: Infliximab (Biological)
Supportive Care (standard of care, sample collection, FMT)
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
干预措施: Prednisone (Drug)
Supportive Care (standard of care, sample collection, FMT)
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
干预措施: Vedolizumab (Biological)
Supportive Care (standard of care, sample collection, FMT)
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
干预措施: Biospecimen Collection (Other)
Supportive Care (standard of care, sample collection, FMT)
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
干预措施: Endoscopic Procedure (Procedure)
Supportive Care (standard of care, sample collection, FMT)
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
干预措施: Fecal Microbiota Transplantation (Procedure)
Supportive Care (standard of care, sample collection, FMT)
PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Difference in stool microbiome pattern
时间窗: Up to 1 year
The primary endpoint is alpha diversity of bacteria species (measured using inverse Simpson index). It is a measure of diversity which takes into account the number of species present, as well as the relative abundance of each species. As species richness and evenness increase, so diversity increases.
Incidence of adverse events (AE) of fecal microbiota transplantation (FMT) (Project 3)
时间窗: Up to 1 year
Adverse events will be recorded by Common Terminology Criteria for Adverse Events version 5 as well as FMT-specific events. All events will be recorded with grade and attribution to FMT. Adverse events that are related to fecal microbiota transplantation will be summarized using frequency and percentage by AE grade, type and attributions.
次要结局
- Immune profile factors associated with onset of ICPI-related colitis in blood and colon tissue(Up to 1 year)
- Endoscopic and histologic features of ICPI-related colitis before and after medical treatment(Baseline up to 1 year)
- Changes of ICPI-related symptoms(Up to 1 year)
- Changes of quality of life (QoL)(Up to 1 year)
- Cytokine features that are associated with good response to FMT(Up to 1 year)
- Changes of endoscopic and histologic features of ICPI-related colitis before and after fecal microbiota transplantation(Baseline up to 1 year)
- Genetic factors associated with onset of ICPI-related colitis in blood and colon tissue(Up to 1 year)