Infliximab for Colitis in Melanoma
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: Immune suppressing biologics
Disqualifiers: Inflammatory bowel disease, Hepatitis B, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?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?
Will I have to stop taking my current medications?
The trial requires that you stop taking any immune suppressing biologic medications at least 4 weeks before joining. If you're on systemic corticosteroids or other immune suppressing medications, you must not have used them in the past 10 days.
What evidence supports the effectiveness of the drug infliximab for treating colitis in melanoma patients?
Research shows that infliximab, a drug used to treat inflammation, was effective in managing severe colitis (inflammation of the colon) caused by cancer treatments in melanoma patients. In a study, infliximab successfully treated colitis in most patients, and it did not negatively impact their cancer treatment outcomes.
12345Is infliximab safe for treating colitis in melanoma patients?
Infliximab has been used safely in patients with severe colitis caused by melanoma treatments, with most patients responding well after just one infusion. It is generally considered safe, but like all medications, it may have side effects, and its use should be monitored by healthcare professionals.
12367How does the drug infliximab differ from other treatments for colitis in melanoma patients?
Infliximab is unique because it is used to treat severe colitis caused by immune checkpoint inhibitors in melanoma patients, especially when steroids are not effective. It works by blocking tumor necrosis factor alpha (TNFα), a substance in the body that causes inflammation, and is administered intravenously, often leading to successful remission without affecting melanoma outcomes.
12389Eligibility Criteria
This trial is for adults over 18 with stage III/IV melanoma who've had recent treatment with specific immune therapies and are experiencing moderate to severe diarrhea as a side effect. It's not for those on other immune suppressants, have certain infections or hepatitis, inflammatory bowel diseases, or previous bad reactions to infliximab or steroids.Inclusion Criteria
I am 18 years old or older.
I have been diagnosed with advanced stage skin cancer.
I had severe diarrhea that stopped my immunotherapy treatment.
+2 more
Exclusion Criteria
I have a history of inflammatory bowel disease or related conditions.
I am currently being treated for a bacterial infection or have a systemic fungal infection.
I am currently taking medication for an immune system side effect.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either infliximab or corticosteroids for the treatment of ICI colitis over 7 weeks
7 weeks
Weekly follow-ups (in-person or phone)
Follow-up
Participants are monitored for safety and effectiveness after treatment, with medical records reviewed every 6 months
6 months
Long-term Follow-up
Participants' progression-free survival and overall survival are monitored
24 months
Participant Groups
The study compares infliximab against steroids in treating colitis caused by cancer immunotherapy. Participants will be randomly assigned to receive either infliximab or steroids and monitored for steroid-free disease resolution after 7 weeks.
2Treatment groups
Experimental Treatment
Group I: InfliximabExperimental Treatment1 Intervention
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 II: CorticosteroidsExperimental Treatment2 Interventions
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.
Infliximab is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Remicade for:
- Ankylosing Spondylitis
- Crohn's Disease
- Ulcerative Colitis
- Psoriatic Arthritis
- Rheumatoid Arthritis
- Plaque Psoriasis
🇺🇸 Approved in United States as Remicade for:
- Ankylosing Spondylitis
- Crohn's Disease
- Ulcerative Colitis
- Psoriatic Arthritis
- Rheumatoid Arthritis
- Plaque Psoriasis
🇨🇦 Approved in Canada as Remicade for:
- Ankylosing Spondylitis
- Crohn's Disease
- Ulcerative Colitis
- Psoriatic Arthritis
- Rheumatoid Arthritis
- Plaque Psoriasis
🇯🇵 Approved in Japan as Remicade for:
- Ankylosing Spondylitis
- Crohn's Disease
- Ulcerative Colitis
- Psoriatic Arthritis
- Rheumatoid Arthritis
- Plaque Psoriasis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General Hospital Cancer CenterBoston, MA
Dana-Farber Cancer InstituteBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
Dana-Farber Cancer InstituteCollaborator
References
Infliximab for ipilimumab-induced colitis: A series of 13 patients. [2018]To review the outcomes of metastatic melanoma patients treated with infliximab for severe steroid-refractory colitis secondary to ipilimumab therapy.
Incidence and Clinical Impact of Anti-TNFα Treatment of Severe Immune Checkpoint Inhibitor-induced Colitis in Advanced Melanoma: The Mecolit Survey. [2023]Immune checkpoint inhibitors (ICI) significantly improve overall survival (OS) in patients with advanced melanoma, but immune-related colitis may occur and warrant anti-tumor necrosis factor α (TNFα) treatment in severe forms. A nationwide, multicenter retrospective survey was conducted to assess both, the real-life incidence of grade 3/4 ICI-induced colitis treated with anti-TNFα, in patients with advanced melanoma, and the consequence of this therapeutic strategy on disease outcome. All patients with advanced melanoma treated with anti-TNFα agents for severe ICI-related colitis in the participating centers were included. Relative incidence was calculated according to the total number of patients treated with ICI in network centers during the period of inclusion. The possible impact of anti-TNFα treatment on disease outcome was evaluated through comparison of objective response rate, progression-free survival, and OS with pivotal literature data. Twenty-seven patients from 13 tertiary referral centers were included. Overall, severe ICI-related colitis treated with anti-TNFα occurred in 1% of patients with advanced melanoma, mostly with ipilimumab. Infliximab was successfully used in all patients but 1, mostly after 1 infusion. OS and progression-free survival of 12 and 3 months, respectively, were observed in these patients, along with an objective response rate of 41% at 12 months. This survey shows a low real-life incidence of severe colitis requiring anti-TNFα. Response rates to immunotherapy and survival data do not appear to significantly differ from those observed in pivotal studies. Severe ICI-induced colitis requiring anti-TNFα treatment appears to be a rare event in advanced melanoma, and infliximab does not seem to adversely affect disease outcome.
Risk Factors and Clinical Outcomes in Patients with IBD with Melanoma. [2023]Patients with inflammatory bowel disease (IBD) are at increased risk to develop malignant melanoma and this risk may increase with use of anti-tumor necrosis factor (TNF) therapy. Impaired survival of immunosuppressed melanoma patients is reported in transplant and rheumatology patients. This study aims to (1) identify risk factors for melanoma development in patients with IBD, (2) compare clinical characteristics of melanoma in patients with IBD to the general population, and (3) assess the influence of immunosuppressive medication on survival.
Association of immune-checkpoint inhibitors and the risk of immune-related colitis among elderly patients with advanced melanoma: real-world evidence from the SEER-Medicare database. [2022]The use of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) therapy (ipilimumab) and anti-programmed cell-death 1 (anti-PD1) agents (nivolumab and pembrolizumab) in advanced melanoma have been associated with immune-related adverse events (irAEs) including colitis. We aimed to estimate the incidence and the risk of colitis in elderly patients with advanced melanoma treated with anti-CTLA4 and anti-PD1 in the real-world setting.
Melanoma and non-melanoma skin cancer in inflammatory bowel disease patients following tumor necrosis factor-α inhibitor monotherapy and in combination with thiopurines: analysis of the Food and Drug Administration Adverse Event Reporting System. [2022]Reports have shown an increased risk of melanoma skin cancer (MSC) with exposure to tumor necrosis factor alpha (TNF-α) inhibitors and non-melanoma skin cancer (NMSC) with thiopurine exposure in inflammatory bowel disease (IBD) patients. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) we sought to evaluate the odds of developing MSC and NMSC for patients on TNF-α inhibitors as monotherapy and in combination therapy with thiopurines and/or steroids.
Infliximab, azathioprine, or combination therapy for Crohn's disease. [2022]The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.
Adalimumab in Crohn's disease. [2023]Although the advent of infliximab has changed the treatment paradigm and goals in inflammatory bowel diseases (IBD), it does not provide a cure for IBD and recent evidence has demonstrated that the immunogenicity of this chimeric anti-TNF antibody is associated with secondary loss of response and intolerance. In ulcerative colitis (UC) the efficacy of infliximab was demonstrated in two large clinical trials, but long-term maintenance efficacy data are lacking. Novel biological agents have entered clinical development and pioneering trials have been reported in the last two years. For Crohn's disease (CD) two anti-TNF agents, the fully human IgG1 anti-TNF monoclonal adalimumab and the humanized pegylated Fab-fragment certolizumab-pegol and the humanized anti alpha4 integrin IgG4 antibody both have demonstrated efficacy as maintenance agents. Adalimumab has been approved to treat active rheumatoid arthritis, psoriatric arthritis, and ankylosing spondylitis, and recently moderate-to-severe luminal CD has been added as an indication for this agent both by the FDA and EMEA. Further evidence is needed to establish the therapeutic potential of adalimumab in fistulizing CD and in UC. The benefit to risk ratio of anti-TNF agents in refractory IBD is clearly positive and since most of the toxicity is class specific, adalimumab is expected to have a safety profile similar to that of infliximab except for adverse events related to infusions.
Successful Treatment of an Immune-Mediated Colitis Induced by Checkpoint Inhibitor Therapy in a Patient with Advanced Melanoma. [2020]Immune checkpoint inhibitors (ICIs) have been used as immunotherapeutic agents in several malignancies because of their ability to modify the T cell-mediated response against tumor cells. Dual checkpoint inhibition improves remission rates in patients with metastatic melanoma compared to monotherapy. However, a higher incidence of toxicity, including immune-related colitis, has been reported before. A 54-year-old female was diagnosed with malignant melanoma on her left upper arm. Because of progressive metastatic disease, a rescue therapy with nivolumab (Opdivo®) 1 mg/kg and ipilimumab (Yervoy®) 3 mg/kg was initiated and a clinical and radiological remission was achieved. Two weeks after completing the third cycle of the ICI therapy, the patient presented with persistent hemorrhagic diarrhea, nausea and abdominal pain. A diagnostic colonoscopy revealed multiple ulcerative lesions and hemorrhagic colitis of the sigmoid and rectum. Due to the ongoing treatment with nivolumab and ipilimumab, the diagnosis of a checkpoint inhibitor-induced colitis was made and immunosuppression with local and systemic steroids, such as mesalazine was initiated. In order to achieve a long-lasting steroids reduction, we decided to start with infliximab (Remicade® 5 mg/kg body weight i.v. every 2 weeks). Clinical remission was achieved and prednisolone could be subsequently discontinued. Infliximab, in combination with mesalazine, could successfully induce a long-lasting remission without steroids. The treatment of ICI-induced colitis did not lead to a reoccurrence of malignant melanoma after 2 years of follow-up.
Infliximab induction regimens in steroid-refractory acute severe colitis: a multicentre retrospective cohort study with propensity score analysis. [2020]Accelerated induction regimens of infliximab have been proposed to improve response rates in patients with steroid-refractory acute severe colitis.