An Investigational Study of Infliximab With Prednisone or Methylprednisolone Versus Prednisone Combination Treatment in Immune Related or Severe Diarrhea in Patients Treated With Yervoy and/or Opdivo

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the effects of Infliximab and oral prednisone versus methylprednisolone and oral prednisone in patients with melanoma, lung cancer, or renal cell carcinoma who have immune related Grade 3-4 diarrhea for up to 3 days or persistent Grade 2 diarrhea for more than 5 days after treatment with Yervoy and/or Opdivo

Official Title
-----------------
A Phase 2, Randomized, Open-Label Study of Infliximab and Lower Exposure Corticosteroids vs Methylprednisolone and Higher Exposure Oral Corticosteroids for the Management of Immune-Related Severe or Persistent Diarrhea in Patients Treated With Yervoy (Ipilimumab) and/or Opdivo (Nivolumab)

Conditions
-----------------
Renal Cell Carcinoma, Melanoma, Lung Cancer

Intervention / Treatment
-----------------
* Drug: Infliximab + Prednisone
* Drug: Methylprednisolone + Prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Subjects must have melanoma or lung cancer or renal cell carcinoma and received ipilimumab or nivolumab as a single treatment or in combination Subject must have NCI common toxicity Grade 3-4 immune-related diarrhea for up to 3 days or persistent Grade 2 diarrhea for more than 5 days Subjects must be discontinued from ipilimumab or nivolumab as monotherapy or with the combination regimen Exclusion Criteria: Subjects who received other anti Cytotoxic T-lymphocytic antigen (CTLA-4) (non-ipilimumab) or other anti-Programmed death-1 (PD-1) (non-nivolumab) treatment Subjects treated with systemic Corticosteroid (CST) within 1 week before randomization and subjects treated with infliximab within 7 weeks before randomization Subjects with known history of tuberculosis Subjects with immunosuppressive disease that require use of systemic steroids or immunosuppressive treatment Subjects allergic to infliximab, inactive components of infliximab, murine proteins and methylprednisolone Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infliximab + Prednisone<br>Infliximab intravenous solution (single dose) + low dose prednisone per oral for 18 days | Drug: Infliximab + Prednisone<br>* Prednisone dose will be decreased every 3 days for 18 days<br>|
| Experimental: Methylprednisolone + Prednisone<br>Methylprednisolone intravenous solution (single dose) + high dose prednisone per oral for 40 days | Drug: Methylprednisolone + Prednisone<br>* Prednisone dose will be decreased every 4 days for 40 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in management of immune related grade 3 and 4 diarrhea as measured by proportion of responders to less than or equal to grade 1 |  | Up to 78 hours | 
| Improvement in management of persistent grade 2 diarrhea as measured by proportion of responders to less than or equal to grade 1 |  | Up to 78 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days to improvement to less than grade 1 diarrhea |  | Randomization up to 12 weeks | 
| Quality of life as measured by European Quality of Life-5 Dimensions Questionnaire (EQ-5D) |  | Up to 12 weeks | 
| Number of hospitalizations |  | Up to 12 weeks | 
| Duration of hospitalizations |  | Up to 12 weeks | 
| Number of patients with adverse events (AEs) |  | Up to 12 weeks | 
| Number of patients with AEs related to steroid use |  | Up to 12 weeks | 
| Number of patients with Gastrointestinal (GI) specific AEs |  | Up to 12 weeks |