Clinical trial NCT06206707: FMT in Checkpoint Inhibitor-mediated Diarrhea and Colitis
Official title: Faecal Microbiota Transplantation for Immune Checkpoint Inhibitor-mediated Diarrhea/Colitis: a Randomised, Double-blind Pilot Efficacy and Safety Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diarrhea
Colitis
Malignant Melanoma
Kidney Cancer
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2024-01-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a double-blind, placebo controlled, randomised trial
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to determine the outcome of patients with immune checkpoint inhibitor-mediated diarrhea/colitis (IMC) treated with faecal microbiota transplantation (FMT) in a randomised, placebo-controlled trial.

The aim of the present study is to assess the feasibility, pilot efficacy, and safety of FMT for patients with IMC.

Participants will be treated two times with capsule FMT or placebo capsules in a 1:1 ratio. The intervention treatment will be an add-on to the patients' standard treatment for IMC.

Researchers will compare the FMT-treated group to the placebo-treated group to see if FMT promotes remission of IMC.

Detailed description: As above

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or above.
2. Histologically proven diagnosis of malignant melanoma and/or kidney cancer.
3. Treatment with any immune checkpoint inhibitor (Nivolumab, Pembrolizumab, Cemiplimab, Atezolizumab, Durvalumab, Avelumab, Ipilimumab), alone or in combination, within the last 8 weeks.
4. Grade 2 or higher CTCAE diarrhea, of which at least 3 stools are Bristol chart score 6-7.
5. Negative PCR for enteric pathogens including C. difficile, after the onset of diarrhea.
6. Signed written informed consent.

Exclusion Criteria:

1. Diagnosed bacterial infection requiring antibiotic treatment at inclusion.
2. Pregnancy or breastfeeding. Pregnancy ruled out by male sex, postmenopausal women or a negative choriogonadotropin (hCG) urine test.
3. Primary diarrheal disease pre-existing to the immune checkpoint inhibitor treatment, including inflammatory bowel disease.
4. Unable to ingest capsules.
5. Unable to understand written or oral patient information.

Primary outcomes:
measure: Clinical remission of immune-mediated diarrhea
timeFrame: At 42 days after intervention treatment
Secondary outcomes:
measure: Remission of diarrhea defined by CTCAE
timeFrame: At 42 days after intervention treatment
measure: Remission of colitis defined by CTCAE
timeFrame: At 42 days after intervention treatment
measure: Therapy response of FMT
timeFrame: Up to 12 weeks after intervention treatment
measure: Number of days until CTCAE diarrhea grade 1
timeFrame: Up to 12 weeks after intervention treatment
measure: Number of days until resolution of diarrhea
timeFrame: Up to 12 weeks after intervention treatment
measure: Incidence of fecal microbiota transplantation (FMT)-related adverse events
timeFrame: At 42 days after intervention treatment
measure: Incidence of fecal microbiota transplantation (FMT)-related serious adverse events
timeFrame: At 12 weeks after intervention treatment
measure: Faecal microbiota composition
timeFrame: Up to 6 weeks after intervention treatment
measure: Gut mucosa-associated microbiome
timeFrame: Up to 6 weeks after intervention treatment
measure: Faecal-calprotectin
timeFrame: Up to 6 weeks after intervention treatment
measure: Blood immunological parameters
timeFrame: Up to 6 weeks after intervention treatment
measure: Hospitalisation
timeFrame: Up to 12 weeks after intervention treatment
measure: Colectomy
timeFrame: Up to 12 weeks after intervention treatment
measure: Mortality
timeFrame: Up to 12 weeks after intervention treatment
measure: Accumulated steroid dose
timeFrame: Up to 12 weeks after intervention treatment
measure: Resumption of immune checkpoint inhibitor therapy
timeFrame: Up to 12 weeks after intervention treatment
measure: Response to immune checkpoint inhibitor therapy
timeFrame: Up to 12 weeks after intervention treatment
measure: Patient and physician perceptions of FMT treatment
timeFrame: At 42 days after intervention treatment
measure: Health-related quality of life
timeFrame: At 42 days after intervention treatment
measure: Endoscopic response
timeFrame: Up to 6 weeks after intervention treatment
measure: Endoscopic remission
timeFrame: Up to 6 weeks after intervention treatment
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: University of Aarhus
name: Christian L Hvas, PhD
role: PRINCIPAL_INVESTIGATOR
References: