Immune-Mediated Colitis Clinical Trial
Official title:
Open Label Randomized Controlled Clinical Trial of Vedolizumab Versus Conventional Treatment for Checkpoint Inhibitor Induced Colitis
This is an open label randomized trial to evaluate the efficacy and treatment duration with vedolizumab to patients with immune mediated colitis. The trial will include 82 patients randomized into two arms, either standard treatment with prednisolone (plus infliximab in severe cases) or vedolizumab treatment up front.
Status | Recruiting |
Enrollment | 82 |
Est. completion date | April 2025 |
Est. primary completion date | April 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Patients with solid tumors treated with PD-1, PD-L1 and /or CTLA-4 inhibitors and where IrAE colitis is preventing further treatment with check point inhibitors - IrAE colitis where the oncologist suggests treatment with tablet or IV corticosteroids (prednisolone or equivalent) - Negative pregnancy test in fertile women - Age = 18. Exclusion Criteria: - Any ongoing infectious disease, including GI infections - Neutropenia within the last month - Known allergy towards vedolizumab or Infliximab - Severe heart failure, NYHA grade 3-4 - Colorectal cancer - Other IrAEs requiring systemic treatment with either prednisolone (> 10 mg daily or equivalents) or other immunosuppressive medications within 14 days before study drug administration - Females of childbearing potential or males of reproductive potential who are not willing to use an effective method of contraception, such as oral, injected, or implanted hormonal methods of contraception, intrauterine device or intrauterine system, condom in combination with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, creamer suppository, male sterilization, or true abstinence throughout study and for a minimum of 3 months after study drug therapy |
Country | Name | City | State |
---|---|---|---|
Denmark | Herlev University Hospital | Herlev |
Lead Sponsor | Collaborator |
---|---|
University of Copenhagen |
Denmark,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | T-cell response | Tumor-specific T cell responses in patients under systemic prednisolone treatment or treatment with infliximab or vedolizumab. | Change from week 0 to week 15. | |
Other | pharmacogenomic | Pharmacogenomic profiling of genes correlated to ICPI colitis treatment outcome | week 0 to week 30 | |
Other | Omics | Omics profiles from blood (buffy coat RNA sequencing transcriptome), urine (metabonome), feces (microbiota, metabonome), and colonic biopsies (RNA sequencing transcriptome) | week 0 to week 30. | |
Other | Single cells | Single cell RNAseq profiles of PMBCs and single cell RNAseq profiles of immune cells isolated from the mucosal area | week 0 to week 30 | |
Other | Subgroup analysis | all outcomes in the subgroup of patients with verified colitis defined as f-calprotectin >200 or endoscopic mayoscore > 0 or intestinal biopsies with evidence of enterocolitis | week 30 | |
Other | subgroup analysis | all outcomes mentined above in patients without the need of prednisolone during screening | week 30 | |
Primary | dose of prednisolone | The cumulative dose of corticosteroids (tablets and IV) due to IrAE colitis at week 30 | Week 30 | |
Secondary | clinical remission | Clinical remission at week 2, 10 and 30*, defined as a partial Mayo score = 2. | week 2 | |
Secondary | clinical remission | Clinical remission at week 2, 10 and 30*, defined as a partial Mayo score = 2. | week 10 | |
Secondary | clinical remission | Clinical remission at week 2, 10 and 30*, defined as a partial Mayo score = 2. | week 30 | |
Secondary | time to response | Time to clinical remission and eventual relapse of GI symptoms (measured by patient reported stool chart registered the first 30 days). | 30 days | |
Secondary | partial Mayo score | Response defined as decrease in partial Mayo score = 30 % at week 2, 10 and 30 | week 2 | |
Secondary | partial Mayo score | Response defined as decrease in partial Mayo score = 30 % at week 2, 10 and 30 | week 10 | |
Secondary | partial Mayo score | Response defined as decrease in partial Mayo score = 30 % at week 2, 10 and 30 | week 30 | |
Secondary | change in scores | change between clinical scores | change from week 0 and 10 and 30 | |
Secondary | fecal calprotectin | change between fecal-calprotectin | change from week 0 and 10 and 30 | |
Secondary | IUS | Intestinal ultrasound | change from week 0 and 10 and 30 | |
Secondary | endoscopy | endoscopy | change from week 0 and 30 | |
Secondary | change in scores | biochemistry | change from week 0 and 10 and 30 | |
Secondary | Life qualtity | Changes in quality of life | change from week 0 and 10 and 30 | |
Secondary | steroid use for other reasons | Corticosteroid use for non-intestinal indications. | During the 30 weeks period | |
Secondary | ICPI treatment | The proportion of patients able to continue ICPI treatment at any time after inclusion and until week 30*. | Week 30 | |
Secondary | steroid free remission | Proportion of patients in corticosteroid (tablets or IV) free remission at week 10 and 30* and the cumulative dose corticosteroid at week 10 | week 10 | |
Secondary | steroid free remission | Proportion of patients in corticosteroid (tablets or IV) free remission at week 10 and 30* | week 30 | |
Secondary | ICPI treatment | Proportion of patients able to continue ICPI treatment at any time after inclusion and until week 30 | week 30 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04768504 -
Tofacitinib for the Treatment of Refractory Immune-related Colitis From Checkpoint Inhibitor Therapy- TRICK Study
|
Phase 2 |