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

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02763761

Collaborator

(none)

Enrollment

Locations

Arms

7.5

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma Melanoma Lung Cancer	Drug: Infliximab + Prednisone Drug: Methylprednisolone + Prednisone	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Aug 16, 2016

Anticipated Primary Completion Date :

Mar 31, 2017

Anticipated Study Completion Date :

Mar 31, 2017

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Infliximab + Prednisone

Infliximab intravenous solution (single dose) + low dose prednisone per oral for 18 days

Drug: Infliximab + Prednisone

Prednisone dose will be decreased every 3 days for 18 days

Experimental: Methylprednisolone + Prednisone

Methylprednisolone intravenous solution (single dose) + high dose prednisone per oral for 40 days

Drug: Methylprednisolone + Prednisone

Prednisone dose will be decreased every 4 days for 40 days

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Los Angeles	Los Angeles	California	United States	90024
2	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
3	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
4	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322-1013
5	University of Louisville	Louisville	Kentucky	United States	40202
6	University of Michigan	Ann Arbor	Michigan	United States	48109
7	Atlantic Health System	Morristown	New Jersey	United States	07962
8	Local Institution	Albuquerque	New Mexico	United States	87131
9	NYU Langone Medical Center	New York	New York	United States	10016
10	Huntsman Cancer Institute at The University of Utah	Salt Lake City	Utah	United States	84112