Melanoma Stage IV Clinical Trial
Official title:
Phase II Study of Infliximab for the Treatment of Immune Checkpoint Inhibitor Colitis
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?
Status | Recruiting |
Enrollment | 42 |
Est. completion date | June 30, 2030 |
Est. primary completion date | June 30, 2030 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Massachusetts General Hospital Cancer Center | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Massachusetts General Hospital | Dana-Farber Cancer Institute |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Proportion of Participants with Treatment Related Adverse Events as Assessed by CTCAE 5. | National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | 6 Months | |
Secondary | The proportion of patients requiring secondary immune suppression-Infliximab | patients randomly assigned to infliximab, secondary immune support will be defined as requiring subsequent treatment with steroids. The proportions of patients in each treatment arm requiring secondary immune suppression will be summarized and presented with 90% exact binomial confidence intervals | 7 Weeks | |
Secondary | The proportion of patients requiring secondary immune suppression-Steroids | patients randomly assigned to steroids, secondary immune support will be defined as requiring subsequent treatment with steroids. The proportions of patients in each treatment arm requiring secondary immune suppression will be summarized and presented with 90% exact binomial confidence intervals | 7 Weeks | |
Secondary | Time to steroid-free remission | The initial analysis of steroid-free remission will be based on cumulative incidence (1-Kaplan-Meier estimates). | 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 | |
Secondary | Rate of Symptom Remission at 72 hours | The proportion of patients in each treatment arm who have colitis symptom reduction to grade-1 or less within 72 hours of starting randomized treatment will be summarized and presented with 90% exact binomial confidence intervals. The treatment arms will be compared using Fisher's exact tests. | 72 hours | |
Secondary | Rate of Symptom Remission at 4 Weeks | The proportion of patients in each treatment arm who have colitis symptom reduction to grade-1 or less within 72 hours of starting randomized treatment will be summarized and presented with 90% exact binomial confidence intervals. The treatment arms will be compared using Fisher's exact tests. | 4 weeks | |
Secondary | Proportion of patients with colectomy or colitis-specific mortality | The proportions of patients with colectomy or colitis-specific mortality (investigator assessed) will be presented by treatment arm with 90% exact binomial confidence intervals | 7 weeks | |
Secondary | Cumulative steroid exposure | Cumulative steroid exposure over time for each patient will be calculated by adding the number of doses multiplied by strength of dose over the total follow-up time. Steroid exposure will be summarized descriptively for each treatment arm, and compared using a Wilcoxon rank-sum test.
With 20 patients per treatment arm, a Wilcoxon rank-sum test will have 80% power to detect a 41difference in cumulative steroid exposure that is 0.85 times the common standard deviation, assuming a one-sided, type-I error of 10 |
7 weeks | |
Secondary | Progression Free Survival | summarized using the method of Kaplan-Meier and compared using stratified log-rank tests | duration of time from start of randomization to time of progression or death, whichever occurs first or up to 24 months. | |
Secondary | Overall Survival | summarized using the method of Kaplan-Meier and compared using stratified log-rank tests | the duration of time from start of randomization to time of death or up to 24 months | |
Secondary | Overall Response Rate | Response rates will be summarized by treatment arm and presented with 90% exact binomial confidence intervals. The comparison of response rates between treatment arms will use Fisher's exact test | proportion of evaluable patients who achieve either a (complete response) CR or (partial response) PR or up to 24 Months |
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