Phase II Study of Infliximab for the Treatment of Immune Checkpoint Inhibitor Colitis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Proportion of patients with Steroid-Free Colitis
研究概览
简要总结
The goal of this clinical trial is to compare the safety and effectiveness of infliximab compared to steroids for the treatment of immune checkpoint inhibitor-induced colitis (ICI colitis) in patients with stage III/IV skin cancer.
The main questions this study aims to answer are:
- How many patients treated with infliximab experience steroid-free disease resolution after 7 weeks?
- How many patients treated with steroids experience steroid-free disease resolution after 7 weeks?
详细描述
This is a phase II, randomized, signal-detection trial to evaluate the efficacy and safety of the drugs infliximab, methylprednisolone, and prednisone to manage the side of effect of colitis caused by immune checkpoint inhibitors (ICIs) that target a protein called CTLA-4. An example of one of these ICIs is ipilimumab, which has been approved by the FDA to treat metastatic melanoma.
The names of the treatments involved in this study are:
- Infliximab
- Methylprednisolone
- Prednisone
The FDA has approved infliximab, methylprednisolone, and prednisone to treat many conditions affecting the immune system, including colitis.
Participants will receive a CTLA-4 inhibitor, like ipilimumab, and any other cancer treatments as part of their regular care for stage III/IV skin cancer at the discretion of treating oncologist.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Stage III/IV skin cancer
- •Treatment with CTLA-4 inhibitor alone or in combination with PD-1or PD-L1 blockade within the past 8 weeks
- •Clinically significant diarrhea resulting in the decision to pause immunotherapy treatment
- •Endoscopically visible colitis (Mayo 1-3) at the time of screening
排除标准
- •Prior history of inflammatory colitis related to immune checkpoint inhibitors requiring treatment with > 10 mg/day of prednisone or equivalent, or any other immunosuppressive medication
- •Concurrent immune-related Adverse Event (irAE) requiring treatment with systemic corticosteroids (dose equivalent of prednisone 10 mg/day or higher) or another systemic immune suppressing medication within the past 10 days
- •Current use of any immune suppressing biologic medication, or use within the last 4 weeks; immune stimulating medications such as checkpoint blockade are explicitly permitted
- •Current use of combination treatment with an investigation immunotherapy targeting a pathway other than PD-1 or PD-L1, concurrent chemotherapy, or targeted therapy
- •Previous adverse reaction to infliximab or corticosteroids
- •Colonic perforation or abscess present at the time of screening
- •History of Hepatitis B or C with a positive viral load, untreated mycobacterium tuberculosis, or active herpes zoster infection
- •Current bacterial infection requiring antibiotic treatment, or systemic fungal infection
- •Prior history of inflammatory bowel disease, microscopic colitis or segmental colitis associated with diverticulosis
- •Received more than 3 doses of systemic corticosteroids, or receive dsystemic corticosteroids at a dose exceeding 2mg/kg methylprednisolone or equivalent, within 72 hours prior to endoscopy
研究组 & 干预措施
Infliximab
Patients randomized to this arm will receive IV infliximab regardless of whether they are hospitalized due to their colitis.
- Infliximab: Predetermined dose of intravenous infliximab, up to 3 times over 7 weeks
- Crossover for inadequate response: Patients who do not respond to initial treatment within 3 days with a decrease in symptoms by one grade, or who do not improve to grade 2 or less symptoms by 5 days will add combination therapy from the other treatment arm (corticosteroids) at full initial dosing.
干预措施: Infliximab (Drug)
Corticosteroids
Patients randomized to this arm will receive IV steroids or oral steroids depending on whether the severity of their colitis requires hospitalization ("inpatient").
- Inpatient: Predetermined intravenous dose of methylprednisolone, 2x daily up until patients can safely be transitioned to an oral prednisone taper
- Outpatient: Predetermined oral dose of predisone, daily over 7 weeks
Crossover for inadequate response: Patients who do not respond to initial treatment within 3 days with a decrease in symptoms by one grade, or who do not improve to grade 2 or less symptoms by 5 days will add combination therapy from the other treatment arm (infliximab) at full initial dosing.
干预措施: Prednisone (Drug)
Corticosteroids
Patients randomized to this arm will receive IV steroids or oral steroids depending on whether the severity of their colitis requires hospitalization ("inpatient").
- Inpatient: Predetermined intravenous dose of methylprednisolone, 2x daily up until patients can safely be transitioned to an oral prednisone taper
- Outpatient: Predetermined oral dose of predisone, daily over 7 weeks
Crossover for inadequate response: Patients who do not respond to initial treatment within 3 days with a decrease in symptoms by one grade, or who do not improve to grade 2 or less symptoms by 5 days will add combination therapy from the other treatment arm (infliximab) at full initial dosing.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Proportion of patients with Steroid-Free Colitis
时间窗: 7 weeks
Proportion of Patients with Steroid-Free Colitis at seven weeks with steroid-free colitis remission defined as less than 7.5 mg a day of prednisone or equivalent and grade-1 or lower symptoms.
次要结局
- Proportion of Participants with Treatment Related Adverse Events as Assessed by CTCAE 5.(6 Months)
- The proportion of patients requiring secondary immune suppression-Infliximab(7 Weeks)
- The proportion of patients requiring secondary immune suppression-Steroids(7 Weeks)
- Time to steroid-free remission(randomization to grade-1 or lower symptoms of colitis and less than 7.5 mg a day of prednisone or equivalent or up to 6 months)
- Rate of Symptom Remission at 72 hours(72 hours)
- Rate of Symptom Remission at 4 Weeks(4 weeks)
- Proportion of patients with colectomy or colitis-specific mortality(7 weeks)
- Cumulative steroid exposure(7 weeks)
- Progression Free Survival(duration of time from start of randomization to time of progression or death, whichever occurs first or up to 24 months.)
- Overall Survival(the duration of time from start of randomization to time of death or up to 24 months)
- Overall Response Rate(proportion of evaluable patients who achieve either a (complete response) CR or (partial response) PR or up to 24 Months)
研究者
Michael Dougan
Principal Investigator
Massachusetts General Hospital