Early Vedolizumab as First-Line for Immune-Related Colitis Therapy Trial (EVITA)

Early Concomitant Vedolizumab as First-Line for Immune-Related Colitis Therapy Trial

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

Study Overview

• Status: Recruiting
• Conditions: Immune Checkpoint Inhibitor-Related Colitis
• Intervention / Treatment: Drug: Vedolizumab 300 MG Injection [Entyvio]; Drug: Prednisone (and methylprednisolone); Other: Placebo Prednisone Capsules; Drug: Placebo for Sulfamethoxazole-Trimethoprim; Drug: Prednisone Taper; Other: Placebo Vedolizumab; Other: Sulfamethoxazole-Trimethoprim

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shilpa Grover, MD, MPH; Phone Number: 6177326389; Email: sgrover@bwh.harvard.edu
• Study Contact Backup: Name: Seonyoung Goo; Email: sgoo@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Shilpa Grover, MD, MPH; Phone Number: 617-632-6389; Email: sgrover@bwh.harvard.edu
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Elad Sharon; Email: elad_sharon@dfci.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.
• Concurrent immune-related adverse event requiring systemic steroids or systemic immunosuppression within 2 weeks.
• Colonic perforation or abscess.
• Partial or complete bowel obstruction within the last 3 months, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction.
• Active Clostridium difficile or other colonic infection.
• Concurrent hepatitis B or C infection.
• History of untreated tuberculosis and/or positive quantiferon/Tspot test without previous tuberculosis prophylaxis, or untreated active infection with mycobacterium tuberculosis.
• Active or known prior infection with nontuberculous mycobacteria (NTM).
• Unable or unwilling to undergo a colonoscopy/flexible sigmoidoscopy.
• Inpatient status, though patients can be screened while inpatients, they must be outpatient for the planned treatment of ICI colitis.
• History of total proctocolectomy.
• Female patients who are pregnant or breastfeeding or plan to become pregnant in the next 6 months.
• Patients who are unable to give informed consent.
• Previous SARS-CoV-2 infection within 10 days for mild infections or 20 days for severe/critical illness prior to first Vedolizumab dose.
• Unable to adhere to protocol requirements.
• Any condition that the physician investigators deem unsafe, including other conditions or medications that the investigator determines will put the subject at greater risk from vedolizumab plus brief course of steroids.
• Allergy to sulfamethoxazole-trimethoprim.
• Weight greater than 120 kg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Vedolizumab 300 MG Injection [Entyvio]; This is a biologic medication to treat colitis; Other Names: Entyvio; Drug: Prednisone (and methylprednisolone); This is a steroid; Other: Placebo Prednisone Capsules; Placebo for Prednisone; Drug: Placebo for Sulfamethoxazole-Trimethoprim; Placebo for antibiotic (Sulfamethoxazole-Trimethoprim) Antibiotic. Only if on >21 days of prednisone/placebo
Active Comparator: 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.	Drug: Prednisone (and methylprednisolone); This is a steroid; Drug: Prednisone Taper; This is a tapering dose of prednisone; Other: Placebo Vedolizumab; Placebo for Vedolizumab; Other: Sulfamethoxazole-Trimethoprim; Antibiotic if on >21 days of steroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steroid-free remission rate	Defined as less than 10 mg of prednisone/day and grade 1 or lower diarrhea symptoms without the use of additional biologic rescue medication.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steroid-free remission rate	Defined as less than 10 mg of prednisone/day and grade 1 or lower diarrhea symptoms without the use of additional biologic rescue medication.	5 weeks
Change in calprotectin	As compared to baseline	0, 2, 5 and 8 weeks
Cumulative steroid exposure	Steroid dose x Duration of treatment	5 weeks and 8 weeks
Time to steroid-free colitis remission	Defined as the time from the first day of treatment to the first day with less than 10 mg of prednisone/day and grade 1 or lower symptoms.	Up to 12 months
Rate of secondary immunosuppression for management of ICI colitis	Defined as the use of open-label prednisone or biologic rescue medication	5 weeks and 8 weeks
Rate of symptomatic remission	Defined as a reduction in stool frequency to < 4 bowel movements/day at 1 week	5 weeks and 8 weeks
Hospitalization rate	Due to colitis	8 weeks
Rates of colectomy	Due to colitis	8 weeks
Best overall cancer response		8 weeks and 12 months
Overall survival	Defined as time from the first day of protocol treatment to death or last contact date.	Time of death or 12 months
Proportion of participants with an adverse event (AE)	Proportion of participants with an AE through week 5 (±5 days) attributable to ICI colitis treatment	5 weeks
Proportion of participants with an AE	Proportion of participants with an AE through week 8 (±5 days) attributable to ICI colitis treatment	8 weeks
Presence of histologic inflammation		0, 8 weeks
Pattern of histologic inflammation	Categorized as: Active Colitis Pattern, Lymphocytic Pattern, Graft Vs Host Disease Pattern, Mixed Pattern.	0, 8 weeks
Endoscopic resolution of colitis	Rate of endoscopic resolution of colitis will be determined, if endoscopy is performed at 8 weeks	8 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Time to resumption of cancer treatment	12 months

Collaborators and Investigators

• Sponsor: Shilpa Grover, MD, MPH
• Collaborators: Takeda; Dana-Farber/Brigham and Women's Cancer Center
• Investigators: Principal Investigator: Shilpa Grover, MD, MPH, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2025
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: November 1, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Colitis; Immunotherapy Colitis; Immune Checkpoint Inhibitor Colitis; ICI Colitis
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Colitis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Therapeutics; Drug Administration Routes; Drug Therapy; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Amides; Aniline Compounds; Amines; Pyrimidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Benzene Derivatives; Pregnadienetriols; Pregnadienediols; Drug Combinations; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Sulfones; Trimethoprim; Prednisolone; Prednisone; Methylprednisolone; Trimethoprim, Sulfamethoxazole Drug Combination; Injections; vedolizumab
• Other Study ID Numbers: 24-080

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant data from the final research dataset that underlie results in a publication will be shared upon request.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication. Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

IPD Sharing Access Criteria

De-identified participant data from the final research dataset used in the published manuscript may be shared under the terms of a Data Use Agreement. Requests may be directed to sgrover@bwh.harvard.edu

The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No