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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
195
Infliximab is available in vials of 100 mg with pharmaceutical form of concentrate for solution for infusion. Participating sites will ensure availability of infliximab as part of the hospital's standard supply for use in the study.
Methylprednisolone is available in vials of 40 mg. Methylprednisolone is a drug used for standard treatment first line for ir-colitis or diarrhoea CTCAE grade ≥ 3. Participating sites will ensure availability of methylprednisolone for use in the study as part of the hospitals standard supply.
Prednisolone is available in tablets of 25 or 5 mg. Oral corticosteroids are internationally recommended as initial treatment for ir-colitis and ir-diarrhoea CTCAE grade 2 \[24-27\]. Participating sites will ensure availability of prednisolone for use in the study as part of the hospitals' standard supply.
Department of Oncology, Aalborg University Hospital
Aalborg, Denmark
NOT_YET_RECRUITINGDepartment of Oncology Odense University Hospital
Odense, Denmark
RECRUITINGThe Royal Marsden Hospital
London, United Kingdom
NOT_YET_RECRUITINGTime (days) to persistent modified CTCAE grade ≤ 1 ir-colitis/diarrhoea.
Persistent is defined as grade ≤ 1 ir-colitis/diarrhoea for five consecutive days or more with no increase in corticosteroid intake
Time frame: From the first day of grade ≤ 1 ir-colitis/diarrhoea of that period (time frame: seven weeks)
Proportion of study subjects with grade ≤ 1 ir-colitis/diarrhoea at 72 hours.
Time frame: Time frame: 72 hours
Proportion of study subjects with persistent grade ≤ 1 ir-colitis/diarrhoea at three weeks.
Persistent is defined as grade ≤ 1 ir-colitis/diarrhoea for five consecutive days or more
Time frame: 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 a corticosteroid-free clinical remission (grade ≤ 1 ir-colitis/diarrhoea) after seven weeks.
Time frame: Time frame: seven weeks
Proportion of study subjects requiring rescue immunosuppressive medication
Arm A (initial corticosteroid only): infliximab if no improvement to grade ≤ 2 ir-colitis/diarrhoea after 3 days (time frame: seven weeks); Arm B (initial infliximab): second dose infliximab according to physicians decision if no improvement to grade ≤ 2 ir-colitis/diarrhoea after seven days
Time frame: Time frame: seven days
Cumulative corticosteroid exposure
Time frame: Time frame: seven weeks
QoL by means of EORTC-QLQ-C30
A 30-item questionaire developed to assess the quality of life of cancer patients. Item 1-28 is scaled in a 4 scale score from 'not at all' to 'very much'. Item 29-30 is a numeric rating scale from 1 to 7 assessing overall health/quality of life. One denotes very poor and 7 denotes excellent. Measure: changes in quality of life
Time frame: Change in score from baseline to 3, 12, 24, and 52 weeks after randomisation
QoL by means of selected PRO-CTCAE items
A 8 item questionnaire assessing bowel related issues. The scales ranges from eg: Yes/No Never/rarely/occasionally/frequently/almost constant None/mild/moderate/severe/very severe Not at all/a little bit/ somewhat/quit a bit/very much Measure: changes in bowel related symptoms
Time frame: Change in score from baseline to 3, 12, 24, and 52 weeks after randomisation
Proportion of study subjects with treatment related adverse events as assessed by CTCAE v5.0
Time frame: Time frame: 12 weeks
Proportion of study subjects with colectomy or colitis-specific mortality
Time frame: Time frame: seven weeks
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