Clinical trial NCT04305145: Infliximab for Treatment of Immune Checkpoint Inhibitor Colitis
Official title: Phase II Study of Infliximab for the Treatment of Immune Checkpoint Inhibitor Colitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Melanoma Stage III
Melanoma Stage IV
Skin Cancer Stage III
Skin Cancer Stage IV
Drug-Induced Colitis
Drug Toxicity
Immune-related Adverse Event
Keywords: Melanoma
Skin cancer
Drug toxicity
Colitis
Immune checkpoint inhibitor
Immunotherapy toxicity
Immune-related adverse event
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2020-03-12
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of patients with Steroid-Free Colitis
timeFrame: 7 weeks
Secondary outcomes:
measure: Proportion of Participants with Treatment Related Adverse Events as Assessed by CTCAE 5.
timeFrame: 6 Months
measure: The proportion of patients requiring secondary immune suppression-Infliximab
timeFrame: 7 Weeks
measure: The proportion of patients requiring secondary immune suppression-Steroids
timeFrame: 7 Weeks
measure: Time to steroid-free remission
timeFrame: 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
measure: Rate of Symptom Remission at 72 hours
timeFrame: 72 hours
measure: Rate of Symptom Remission at 4 Weeks
timeFrame: 4 weeks
measure: Proportion of patients with colectomy or colitis-specific mortality
timeFrame: 7 weeks
measure: Cumulative steroid exposure
timeFrame: 7 weeks
measure: Progression Free Survival
timeFrame: duration of time from start of randomization to time of progression or death, whichever occurs first or up to 24 months.
measure: Overall Survival
timeFrame: the duration of time from start of randomization to time of death or up to 24 months
measure: Overall Response Rate
timeFrame: proportion of evaluable patients who achieve either a (complete response) CR or (partial response) PR or up to 24 Months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Michael Dougan, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: