Infliximab for Treatment of Immune Checkpoint Inhibitor Colitis

NCT04305145 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-763
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

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?

Conditions

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

Keywords

Melanoma; Skin cancer; Drug toxicity; Colitis; Immune checkpoint inhibitor; Immunotherapy toxicity; Immune-related adverse event

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with Steroid-Free Colitis

  Proportion of Patients with Steroid-Free Colitis at seven weeks with steroid-free colitis remission defined as less than 7.5 mg a day of prednisone or equivalent and grade-1 or lower symptoms.

  7 weeks

Secondary Outcomes (11)

• Proportion of Participants with Treatment Related Adverse Events as Assessed by CTCAE 5.

  6 Months

• The proportion of patients requiring secondary immune suppression-Infliximab

  7 Weeks

• The proportion of patients requiring secondary immune suppression-Steroids

  7 Weeks

• Time to steroid-free remission

  randomization to grade-1 or lower symptoms of colitis and less than 7.5 mg a day of prednisone or equivalent or up to 6 months

• Rate of Symptom Remission at 72 hours

  72 hours

Study Arms (2)

Infliximab

EXPERIMENTAL

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.

Drug: Infliximab

Corticosteroids

EXPERIMENTAL

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.

Drug: Methylprednisolone; Drug: Prednisone

Interventions

Methylprednisolone DRUG

Infusion

Also known as: Solu-Medrol, Duralone, Medralone, Medrol, M-Prednisol

Corticosteroids

Prednisone DRUG

Orally

Also known as: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS

Corticosteroids

Infliximab DRUG

Infusion

Also known as: AVSOLA, Ixifi, Remicade, Renflexis

Infliximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Melanoma; Skin Neoplasms; Drug-Related Side Effects and Adverse Reactions; Colitis

Interventions

Infliximab; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisone

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Chemically-Induced Disorders; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Study Officials

• Michael Dougan, MD, PHD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: August 31, 2020
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Massachusetts General Hospital (MGH) - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)