Treatment of Immune Checkpoint Inhibitor-Related Colitis With Infliximab or Vedolizumab: A Randomized Trial
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Clinical remission/response rate of immune-mediated colitis (IMC)
研究概览
简要总结
This phase I/II trial studies the side effects of infliximab and vedolizumab and to see how well they work in treating inflammation of the colon (colitis) caused by immune checkpoint inhibitor therapy in patients with cancer of the genital and urinary organs (genitourinary) or melanoma. Monoclonal antibodies, such as infliximab or vedolizumab, may help to treat immunotherapy induced colitis/diarrhea. This study may help to identify the optimal treatment strategy for immune checkpoint inhibitor-related colitis in patients with genitourinary cancer or melanoma.
详细描述
PRIMARY OBJECTIVES:
I. To compare the efficacy of infliximab and vedolizumab for clinical remission/response of immune-related diarrhea and/or colitis.
II. To assess the safety and tolerability of the treatment for immune-mediated diarrhea and/or colitis.
SECONDARY OBJECTIVES:
I. To assess the efficacy of infliximab and vedolizumab for clinical remission/response of IMC at 4 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patients who receive any type of immune checkpoint inhibitor (ICI) therapy
- •Patients with peak grade >= 2 immune-related diarrhea and/or colitis (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 within 45 days prior to initiation of study treatment (infliximab/ vedolizumab)
- •Patients with ability to understand and willingness to sign informed consent
- •Patients with genitourinary cancer or melanoma or non-small cell lung cancer
- •No concern for active concomitant GI infection for immune-related diarrhea and/or 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
- •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
排除标准
- •Patients younger than 18 years of age
- •Patients with persistent gastrointestinal infection confirmed with positive testing despite completing 5 days of antibiotics
- •Patients are on concurrent immunosuppressive therapies other than what will be given for colitis
- •Patients with preexisting activehistory of inflammatory bowel disease and/or radiation enterocolitis with active disease status at the time of study treatment initiation
- •Pregnant and breastfeeding women, and
- •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 initiation of study treatment
- •Patients who develop concurrent non-GI toxicity at the time of study treatment initiation
研究组 & 干预措施
Arm II (vedolizumab)
Patients receive vedolizumab IV over 1 hour at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
干预措施: Vedolizumab (Biological)
Arm I (infliximab)
Patients receive infliximab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
干预措施: Infliximab (Biological)
结局指标
主要结局
Clinical remission/response rate of immune-mediated colitis (IMC)
时间窗: At 2 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
The difference of the remission rate between standard of care (infliximab + corticosteroid) and the treatment with vedolizumab + corticosteroid will be calculated along with the 95% confidence interval.
Treatment-related adverse events
时间窗: Within 3 months after initiation of infliximab or vedolizumab
Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.
次要结局
- Recurrent immune-related diarrhea/colitis(Within 3 months after corticosteroid taper)
- Complete weaning of corticosteroid(Within 4 weeks after infliximab or vedolizumab initiation without rebound of IMC)
- Clinical remission/response rate of IMC(At 4 weeks after initiation of infliximab or vedolizumab with corticosteroid taper)