Health TrialsbyHealthPanel

Efficacy and Safety of Infliximab for Immune Checkpoint Inhibitor Induced Colitis

ConditionColitis
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorOdense University Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Untreated mCTCAE grade 2-4 diarrhoea or colitis, or persistent mCTCAE grade 2 diarrhoea after administration of loperamide or equivalent for mCTCAE grade ≤ 2 diarrhoea

No signs of colonic perforation or infection

Age ≥ 18

Understands the nature and purpose of the study and the study procedures and has signed informed consent

Disqualifiers

Prior history of inflammatory bowel disease, colitis, or diarrhoea requiring treatment with any corticosteroid, or any other immunosuppressant medication

Prior history of recurrent bowel disease including symptomatic diverticulosis

Current positive testing for Clostridium difficile or other colonic infection

Current bacterial infection requiring antibiotic treatment, or systemic fungal infection

Trial design

Design model

Parallel

Treatments tested in this trial

  • Infliximab

    Drug

    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

    Drug

    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

    Drug

    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.

Treatment groups

195 Participants
are divided into 2 treatment groups
Group A: Standard of care - MethylprednisoloneActive comparator 2 interventions
Group B: Treatment with infliximabExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Time (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)

Secondary outcomes

1

Proportion of study subjects with grade ≤ 1 ir-colitis/diarrhoea at 72 hours.

Time frame
Time frame: 72 hours
2

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)
3

Proportion of study subjects with a corticosteroid-free clinical remission (grade ≤ 1 ir-colitis/diarrhoea) after seven weeks.

Time frame
Time frame: seven weeks
4

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

Other outcomes

1

Proportion of study subjects with recurrence of ir-colitis/diarrhoea on subsequent reintroduction of ICI.

Time frame
Timeframe: Up to 24 weeks
2

Subgroup analyses stratified for ipilimumab containing ICI for time (days) to persistent grade ≤ 1 ir-colitis/diarrhoea.

Persistent is defined as grade ≤ 1 ir-colitis/diarrhoea for five consecutive days or more.

Time frame
week 3
3

Progression Free Survival stratified by cancer type

Time frame
Time frame: duration of time from start of randomisation to time of progression or death, whichever occurs first or up to 24 months
4

Overall Survival stratified by cancer type

Time frame
Time frame: the duration of time from start of randomisation to time of death or up to 24 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Odense University Hospital

Lead sponsor

Aalborg University Hospital

Collaborator

Royal Marsden NHS Foundation Trust

Collaborator

Source ClinicalTrials.gov
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