Efficacy and Safety of Infliximab for Immune Checkpoint Inhibitor Induced Colitis

Launched by ODENSE UNIVERSITY HOSPITAL · Jul 7, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating whether adding a medication called infliximab to the standard treatment of corticosteroids can help patients with severe inflammation of the colon (known as ir-colitis) caused by immune checkpoint inhibitors. The main goal is to see if this combination treatment can reduce the time it takes for patients to experience less severe symptoms (grade ≤ 1) compared to using corticosteroids alone. Participants in the trial will be randomly assigned to one of two groups: one will receive only corticosteroids, while the other will get both corticosteroids and infliximab.

To be eligible for this study, participants must be at least 18 years old and have specific types of diarrhea or colitis that have not been treated yet. They should not have any active infections or other serious bowel conditions. Patients will undergo various tests, including blood and stool samples, and a procedure called sigmoidoscopy to check the condition of their intestines. It’s important for participants to understand the study and provide consent before joining. This trial is currently recruiting participants, and it’s open to all genders.

Gender

ALL

Eligibility criteria

• • Inclusion Criteria
• • 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
• • Is able to read, understand, and complete questionnaires and daily components of the patient Diary for the study period
• • Histologically confirmed malignant solid tumours
• • Treatment with immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1 or anti-PD-L1) within the past 12 weeks. Immune checkpoint inhibitors can be administered as single agents or as combination therapy with anti-CTLA-4 and anti-PD-1
• • No probability of a concomitant treatment (e.g. laxatives) other than the immune checkpoint inhibitor being the causal drug for the colitis or diarrhoea
• • Prior treatment with immune checkpoint inhibitors is allowed
• • Usage of prednisolone ≤ 10 mg daily for non irAE is allowed
• • Diagnostic work up including screening for viral hepatic infection and QuantiFERON-TB for mycobacterium tuberculosis must be requisitioned but will not need to be reported prior to study enrolment
• • Women of child bearing potential must have a negative serum (preferred) or urine pregnancy test within 72 hours prior to registration.
• • Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e. females who have had evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
• * Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and after the study treatment:
• • for at least 6 months after the last study treatment, or depending on the duration antineoplastic treatment
• * Note: A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
• • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• • Intrauterine device (IUD)
• • Intrauterine hormone-releasing system (IUS)
• • Bilateral tubal occlusion
• • Vasectomized partner
• • Sexual abstinence
• • Exclusion Criteria
• • 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
• • Ongoing antibiotic treatment for any reason
• • Treatment with systemic corticosteroids within the last four weeks prior to study enrolment (daily usage of prednisolone ≤ 10 mg for non irAE conditions is accepted)
• • Concurrent immune-related adverse events requiring immunosuppressant medication of any kind
• • Known hypersensitivity or contraindications to systemic corticosteroids or infliximab
• • Prior history of viral hepatitis with a positive viral load, known untreated mycobacterium tuberculosis, or known active herpes zoster infection