Immune Checkpoint Inhibitor-Related Colitis
Conditions
Keywords
Immunotherapy Colitis, Immune Checkpoint Inhibitor Colitis, ICI Colitis, Colitis
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.
Interventions
This is a biologic medication to treat colitis
This is a steroid
DRUGPrednisone Taper
This is a tapering dose of prednisone
Placebo for Prednisone
OTHERPlacebo Vedolizumab
Placebo for Vedolizumab
Antibiotic if on \>21 days of steroids
DRUGPlacebo for Sulfamethoxazole-Trimethoprim
Placebo for antibiotic (Sulfamethoxazole-Trimethoprim) Antibiotic. Only if on \>21 days of prednisone/placebo
Sponsors
Dana-Farber/Brigham and Women's Cancer Center
Takeda
Shilpa Grover, MD, MPH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steroid-free remission rate | 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
| Measure | Time frame | Description |
|---|---|---|
| Steroid-free remission rate | 5 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. |
| Change in calprotectin | 0, 2, 5 and 8 weeks | As compared to baseline |
| Cumulative steroid exposure | 5 weeks and 8 weeks | Steroid dose x Duration of treatment |
| Time to steroid-free colitis remission | Up to 12 months | 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. |
| Rate of secondary immunosuppression for management of ICI colitis | 5 weeks and 8 weeks | Defined as the use of open-label prednisone or biologic rescue medication |
| Rate of symptomatic remission | 5 weeks and 8 weeks | Defined as a reduction in stool frequency to \< 4 bowel movements/day at 1 week |
| Hospitalization rate | 8 weeks | Due to colitis |
| Endoscopic resolution of colitis | 8 weeks | Rate of endoscopic resolution of colitis will be determined, if endoscopy is performed at 8 weeks |
| Best overall cancer response | 8 weeks and 12 months | — |
| Overall survival | Time of death or 12 months | Defined as time from the first day of protocol treatment to death or last contact date. |
| Proportion of participants with an adverse event (AE) | 5 weeks | Proportion of participants with an AE through week 5 (±5 days) attributable to ICI colitis treatment |
| Proportion of participants with an AE | 8 weeks | Proportion of participants with an AE through week 8 (±5 days) attributable to ICI colitis treatment |
| Presence of histologic inflammation | 0, 8 weeks | — |
| Pattern of histologic inflammation | 0, 8 weeks | Categorized as: Active Colitis Pattern, Lymphocytic Pattern, Graft Vs Host Disease Pattern, Mixed Pattern. |
| Rates of colectomy | 8 weeks | Due to colitis |
Other
| Measure | Time frame |
|---|---|
| Time to resumption of cancer treatment | 12 months |
Countries
United States
Contacts
Primary ContactShilpa Grover, MD, MPH
Backup ContactSeonyoung Goo
Outcome results
None listed