Vedolizumab for Immune Mediated Colitis

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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 prednisolone.
  • - Colitis is defined as: colonoscopy with Mayo grade >0 or histological signs of active ICPI colitis or feces calprotectin >200.
  • - Negative pregnancy test in fertile women.
  • - Age ≥ 18.

Exclusion Criteria:

  • - • Severe ICPI induced colitis requiring hospitalization and IV corticosteroids.
  • - Any ongoing infectious disease, including GI infections.
  • - Neutropenia (< 2.0 10E9/L) within the last month.
  • - Known allergy towards vedolizumab or Infliximab.
  • - Severe heart failure, NYHA grade 3-4.
  • - Colorectal cancer.
  • - Conditions and/or 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04797325
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Copenhagen
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries Denmark
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Immune-Mediated Colitis
Additional Details

Background information Immune check point inhibitors (ICPI) have revolutionized the treatment of a growing number of cancer forms resulting in a rapidly increasing number of patients treated with these drugs within the very recent years. The aim is to allow and boost an immune response towards the neoantigens of neoplastic cells, but the blockage of inhibitory signals might also interfere with normal barriers against the development of autoimmunity or autoimmune-like reactions and thus lead to a number of immune-related adverse events (IrAEs). Gastrointestinal inflammation

  • - typically colitis - is the most common IrAE among ICPI treated patients.
Vedolizumab, a integrin antibody, has been shown to be highly effective in treating ICPI induced colitis with remission rates of 85%. Vedolizumab has a better safety profile than anti-tumor necrosis factor antibodies, including infliximab, with lower risk of infections and tumor development in inflammatory bowel disease patients. Moreover, vedolizumab does not seem to inhibit tumor specific T cell responses in vitro, suggesting that this treatment is also beneficial with regards to tumor response. The hypothesis. Vedolizumab induction and maintenance treatment of patients with ICPI related intestinal symptoms and evidence of colitis: 1. Is effective in inducing remission of the colitis. 2. Reduces the risk of progression from grade 2 to grade 3 or 4 colitis. 3. Reduces the need of systemic corticosteroid. 4. Is not associated with increased risk of tumor progression or other serious adverse events including serious infections. 5. Allows reintroduction/continuation of ICPI treatment. Further it is hypothesized that ICPI induced colitis can be diagnosed and monitored by intestinal bowel ultrasound and treatment response is associated with multi-omics changes in intestinal tissue, tumor tissue, feces, blood, and urine, e.g. peripheral blood mononuclear cells (PBMCs) RNAseq profiles, profiles of single cell RNAseq from isolated immune cells from standard pinch biopsies from the inflamed colon and composition of the microbiota. Lastly, it is hypothesized, that anti-tumor T-cell function is affected in vivo by the medication used to treat ICPI induced colitis, and that this can be assessed by changes in single cell RNAseq profiles of tumor resident T-cells (isolated from tumor biopsies).

Arms & Interventions

Arms

Active Comparator: vedolizumab

Active Comparator: Standard treatment

Interventions

Drug: - Vedolizumab

Repeatedly vedolizumab infusion at week 0, 2, 6, 14, 22

Drug: - Prednisolone

tablet prednisolone plus infliximab in severe cases.

Contact a Trial Team

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International Sites

Herlev University Hospital, Herlev, Denmark

Status

Address

Herlev University Hospital

Herlev, , 2730

Site Contact

Emilie Dahl

emilie.kristine.dahl@regionh.dk

+4538686391

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