Early Concomitant Vedolizumab as First-Line for Immune-Related Colitis Therapy Trial
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Shilpa Grover, MD, MPH
- Enrollment
- 80
- Locations
- 2
- Primary Endpoint
- Steroid-free remission rate
Overview
Brief Summary
The goal of this clinical trial is to compare the effectiveness and safety of Vedolizumab with a short course of steroids compared to standard course of steroids for the treatment of immune checkpoint inhibitor colitis (ICI colitis) in adults.
The main questions it aims to answer are:
- How many patients treated with Vedolizumab and a short course of steroids experience resolution of colitis at 8 weeks.
- How many patients treated with a standard course of steroids experience resolution of colitis at 8 weeks.
Participants will:
Recieve 3 doses of Vedolizumab or a placebo (a look-alike substance that contains no drug) infusions over 6 weeks Receive intravenous Medrol daily for 3 days Receive Prednisone daily for 7 days Receive Prednisone or placebo taper daily Receive Sulfamethoxazole-Trimethoprim or placebo taper daily Weekly checkups and periodic tests
Detailed Description
This is a phase II, randomized trial to evaluate the efficacy and safety of the drugs Vedolizumab, methylprednisolone, and prednisone to manage the side of effect of colitis caused by immune checkpoint inhibitors (ICIs).
The names of the treatments involved in this study are:
- Vedolizumab
- Methylprednisolone
- Prednisone
- Sulfamethoxazole-Trimethoprim
The FDA has approved Vedolizumab, methylprednisolone, and prednisone to treat many conditions affecting the immune system, including colitis.
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 and stool samples will also be collected for research. Any extra samples for research would only be collected only if it is safe for the participant.
Participants will complete weekly follow-ups either over the phone or in-person. During these visits, participants will be asked about any new symptoms or changes in their health, their medications, and their symptoms. Blood for research may be collected at four of these visits if it coincides with a scheduled clinical blood draw.
Participants are expected to be on study treatment for 8 weeks. The study team will review their medical records at 12 months for any changes in their health.
It is expected that approximately 80 people will participate in this research study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •In order to participate in the study, a patient must meet all the following inclusion criteria:
- •Age ≥18 years.
- •Treatment with an ICI for cancer within the past 8 weeks.
- •Confirmed endoscopic/histologic diagnosis of ICI colitis.
- •Grade 2-3 diarrhea by Common Terminology Criteria for Adverse Events.
- •Willing and able to comply with the requirements of the protocol.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Exclusion Criteria
- •Prior history of inflammatory colitis requiring treatment with greater than prednisone 10 mg daily or equivalent or any immunosuppressive medication.
- •Current or recent use of immunosuppressive biologic medication (for any reason including ICI colitis) within 4 weeks.
Exclusion Criteria
- Not provided
Arms & Interventions
Vedolizumab and Short Course of Steroids
Participants in this arm will receive Vedolizumab infusions (3 doses) and steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days). Participants may also receive daily placebo (for Prednisone and Sulfamethoxazole-Trimethoprim).
Intervention: Vedolizumab 300 MG Injection [Entyvio] (Drug)
Vedolizumab and Short Course of Steroids
Participants in this arm will receive Vedolizumab infusions (3 doses) and steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days). Participants may also receive daily placebo (for Prednisone and Sulfamethoxazole-Trimethoprim).
Intervention: Prednisone (and methylprednisolone) (Drug)
Vedolizumab and Short Course of Steroids
Participants in this arm will receive Vedolizumab infusions (3 doses) and steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days). Participants may also receive daily placebo (for Prednisone and Sulfamethoxazole-Trimethoprim).
Intervention: Placebo Prednisone Capsules (Other)
Vedolizumab and Short Course of Steroids
Participants in this arm will receive Vedolizumab infusions (3 doses) and steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days). Participants may also receive daily placebo (for Prednisone and Sulfamethoxazole-Trimethoprim).
Intervention: Placebo for Sulfamethoxazole-Trimethoprim (Drug)
Standard Course of Steroids
Participants in this arm will receive steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days), followed by a steroid (Prednisone) taper. Participants may also receive Sulfamethoxazole-Trimethoprim (an antibiotic). Participants will receive 3 placebo infusions.
Intervention: Prednisone (and methylprednisolone) (Drug)
Standard Course of Steroids
Participants in this arm will receive steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days), followed by a steroid (Prednisone) taper. Participants may also receive Sulfamethoxazole-Trimethoprim (an antibiotic). Participants will receive 3 placebo infusions.
Intervention: Prednisone Taper (Drug)
Standard Course of Steroids
Participants in this arm will receive steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days), followed by a steroid (Prednisone) taper. Participants may also receive Sulfamethoxazole-Trimethoprim (an antibiotic). Participants will receive 3 placebo infusions.
Intervention: Placebo Vedolizumab (Other)
Standard Course of Steroids
Participants in this arm will receive steroids for 10 days (intravenous Medrol daily for 3 days and Prednisone daily for 7 days), followed by a steroid (Prednisone) taper. Participants may also receive Sulfamethoxazole-Trimethoprim (an antibiotic). Participants will receive 3 placebo infusions.
Intervention: Sulfamethoxazole-Trimethoprim (Other)
Outcomes
Primary Outcomes
Steroid-free remission rate
Time Frame: 8 weeks
Defined as less than 10 mg of prednisone/day and grade 1 or lower diarrhea symptoms without the use of additional biologic rescue medication.
Secondary Outcomes
- Steroid-free remission rate(5 weeks)
- Change in calprotectin(0, 2, 5 and 8 weeks)
- Cumulative steroid exposure(5 weeks and 8 weeks)
- Time to steroid-free colitis remission(Up to 12 months)
- Rate of secondary immunosuppression for management of ICI colitis(5 weeks and 8 weeks)
- Rate of symptomatic remission(5 weeks and 8 weeks)
- Hospitalization rate(8 weeks)
- Rates of colectomy(8 weeks)
- Endoscopic resolution of colitis(8 weeks)
- Best overall cancer response(8 weeks and 12 months)
- Overall survival(Time of death or 12 months)
- Proportion of participants with an adverse event (AE)(5 weeks)
- Proportion of participants with an AE(8 weeks)
- Presence of histologic inflammation(0, 8 weeks)
- Pattern of histologic inflammation(0, 8 weeks)
Investigators
Shilpa Grover, MD, MPH
Director Onco-Gastroenterology, Division of Gastroenterology
Brigham and Women's Hospital