Infliximab for Treatment of Immune Checkpoint Inhibitor Colitis

NCT ID: NCT04305145

Last Updated: 2026-01-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-31
• Study Completion Date: 2030-06-30

Brief Summary

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?

Detailed Description

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.

Participants who enroll in this study will undergo one or more flexible sigmoidoscopies or colonoscopies as part of their clinical care. The first of these procedures would occur at the time of study enrollment, and the second may occur after several weeks of treatment at the discretion of the study doctor. During these procedures, biopsies will be collected for clinical purposes as well as for research purposes. Blood will also be collected for research at the time of enrollment and at the time of study completion. Any extra samples for research would only be collected if it is safe for the participant.

Participants will also complete weekly follow-ups either over the phone or in-person that may last about 10 minutes. During these visits, participants will be asked about any new symptoms or changes in their health, their medications, and their GI symptoms. Blood for research may be collected at one or more of these visits if it coincides with a scheduled clinical blood draw.

Participants are expected to be on study treatment for approximately 7 weeks. Once participants complete the study treatment, the study team will review their medical records every 6 months for any changes in their health.

It is expected that about 42 people will take part in this research study.

Conditions

Melanoma Stage III; Melanoma Stage IV; Skin Cancer Stage III; Skin Cancer Stage IV; Drug-Induced Colitis; Drug Toxicity; Immune-related Adverse Event

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: DRUG

Infusion

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.

Group Type: EXPERIMENTAL

Methylprednisolone

Intervention Type: DRUG

Infusion

Prednisone

Intervention Type: DRUG

Orally

Interventions

Infliximab

Infusion

Intervention Type: DRUG

Methylprednisolone

Infusion

Intervention Type: DRUG

Prednisone

Orally

Intervention Type: DRUG

Other Intervention Names

AVSOLA; Ixifi; Remicade; Renflexis; Solu-Medrol; Duralone; Medralone; Medrol; M-Prednisol; Deltasone; Prednicot; predniSONE Intensol; Rayos; Sterapred; Sterapred DS

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18
• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Michael Dougan

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Dougan, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

19-763

Identifier Type: -

Identifier Source: org_study_id