Efficacy and Safety of Infliximab for Immune Checkpoint Inhibitor Induced Colitis: a Multinational, Randomised, Open Label, Phase III Trial - The iCaD Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 195
- 试验地点
- 3
- 主要终点
- Time (days) to persistent modified CTCAE grade ≤ 1 ir-colitis/diarrhoea.
研究概览
简要总结
The goal of this clinical trial is to assess whether the early introduction of biological treatment with a TNF-alpha inhibitor (infliximab) in addition to corticosteroids for severe ir-colitis/diarrhoea will reduce the time to grade ≤ 1 ir-colitis/diarrhoea compared to corticosteroids alone in patients scheduled for ICI treatment for solid tumors and untreated mCTCAE grade 2-4 diarrhoea or colitis.
The main question it aims to answer is:
• Can an early introduction of biological treatment with a TNF-alpha inhibitor (infliximab) in addition to corticosteroids reduce the time to grade ≤ 1 ir-colitis/diarrhoea compared to corticosteroids alone.
Participants will be randomised 1:1:
Arm A: All patients will receive same dose of methylprednisolone i.v. daily. Arm B: Patients allocated to Arm B will in addition receive infliximab i.v. day 1 or 2.
Study patients are evaluated with blood samples, faecal samples and by sigmoidoscopy. Procedures are performed before randomisation and as part of follow up.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Standard of care - Methylprednisolone
Subjects are hospitalised Day 1 and for at least 4 days. It is accepted that participating centres handle the subjects on an outpatient basis as long as all study requirements are met. Methylprednisolone 80 mg intravenously (body weight 40-80 kg; methylprednisolone 1 mg/kg if body weight < 40 or > 80 kg) will be administered from Day 1 until mCTCAE ir-colitis/diarrhoea grade ≤ 2 and hereafter converted to oral prednisolone. During tapering, if ir-colitis/diarrhoea increases from grade 2 to ≥ grade 3, or from grade < 2 to ≥ grade 2, re-assessment including diagnostic workup will be performed, and the patient will be evaluated for rescue infliximab.
干预措施: Methylprednisolone (Drug)
Standard of care - Methylprednisolone
Subjects are hospitalised Day 1 and for at least 4 days. It is accepted that participating centres handle the subjects on an outpatient basis as long as all study requirements are met. Methylprednisolone 80 mg intravenously (body weight 40-80 kg; methylprednisolone 1 mg/kg if body weight < 40 or > 80 kg) will be administered from Day 1 until mCTCAE ir-colitis/diarrhoea grade ≤ 2 and hereafter converted to oral prednisolone. During tapering, if ir-colitis/diarrhoea increases from grade 2 to ≥ grade 3, or from grade < 2 to ≥ grade 2, re-assessment including diagnostic workup will be performed, and the patient will be evaluated for rescue infliximab.
干预措施: Prednisolone (Drug)
Treatment with infliximab
Infliximab will be administered Day 1 or latest Day 2 (within 48 hours). Infliximab infusion is handled as standard by skilled staff. A second dose of infliximab will be administered if ir-colitis/diarrhoea has not resolved to grade ≤ 2 on Day 7. Methylprednisolone 80 mg (body weight 40-80 kg; methylprednisolone 1 mg/kg if body weight < 40 or > 80 kg) intravenously is co-administered from Day 1 until mCTCAE ir-colitis/diarrhoea grade ≤ 2 and hereafter converted to oral prednisolone. Initial dosage of infliximab is 5 mg/kg. Dosage of infliximab for subjects referred to a second dose of infliximab will be left to the discretion of the treating physician. In the event of failure of infliximab, second line biological immunosuppressant treatment will also be left to the discretion of the treating physician.
干预措施: Infliximab (Drug)
Treatment with infliximab
Infliximab will be administered Day 1 or latest Day 2 (within 48 hours). Infliximab infusion is handled as standard by skilled staff. A second dose of infliximab will be administered if ir-colitis/diarrhoea has not resolved to grade ≤ 2 on Day 7. Methylprednisolone 80 mg (body weight 40-80 kg; methylprednisolone 1 mg/kg if body weight < 40 or > 80 kg) intravenously is co-administered from Day 1 until mCTCAE ir-colitis/diarrhoea grade ≤ 2 and hereafter converted to oral prednisolone. Initial dosage of infliximab is 5 mg/kg. Dosage of infliximab for subjects referred to a second dose of infliximab will be left to the discretion of the treating physician. In the event of failure of infliximab, second line biological immunosuppressant treatment will also be left to the discretion of the treating physician.
干预措施: Methylprednisolone (Drug)
Treatment with infliximab
Infliximab will be administered Day 1 or latest Day 2 (within 48 hours). Infliximab infusion is handled as standard by skilled staff. A second dose of infliximab will be administered if ir-colitis/diarrhoea has not resolved to grade ≤ 2 on Day 7. Methylprednisolone 80 mg (body weight 40-80 kg; methylprednisolone 1 mg/kg if body weight < 40 or > 80 kg) intravenously is co-administered from Day 1 until mCTCAE ir-colitis/diarrhoea grade ≤ 2 and hereafter converted to oral prednisolone. Initial dosage of infliximab is 5 mg/kg. Dosage of infliximab for subjects referred to a second dose of infliximab will be left to the discretion of the treating physician. In the event of failure of infliximab, second line biological immunosuppressant treatment will also be left to the discretion of the treating physician.
干预措施: Prednisolone (Drug)
结局指标
主要结局
Time (days) to persistent modified CTCAE grade ≤ 1 ir-colitis/diarrhoea.
时间窗: From the first day of grade ≤ 1 ir-colitis/diarrhoea of that period (time frame: seven weeks)
Persistent is defined as grade ≤ 1 ir-colitis/diarrhoea for five consecutive days or more with no increase in corticosteroid intake
次要结局
- Proportion of study subjects with persistent grade ≤ 1 ir-colitis/diarrhoea at three weeks.(The event will be calculated from the first day of grade ≤ 1 ir-colitis/diarrhoea of that period (time frame: three weeks))
- Proportion of study subjects with grade ≤ 1 ir-colitis/diarrhoea at 72 hours.(Time frame: 72 hours)
- Proportion of study subjects with a corticosteroid-free clinical remission (grade ≤ 1 ir-colitis/diarrhoea) after seven weeks.(Time frame: seven weeks)
- Cumulative corticosteroid exposure(Time frame: seven weeks)
- Proportion of study subjects with treatment related adverse events as assessed by CTCAE v5.0(Time frame: 12 weeks)
- Proportion of study subjects with colectomy or colitis-specific mortality(Time frame: seven weeks)
- Proportion of study subjects requiring rescue immunosuppressive medication(Time frame: seven days)
- QoL by means of EORTC-QLQ-C30(Change in score from baseline to 3, 12, 24, and 52 weeks after randomisation)
- QoL by means of selected PRO-CTCAE items(Change in score from baseline to 3, 12, 24, and 52 weeks after randomisation)