FMT in Checkpoint Inhibitor-mediated Diarrhea and Colitis

Not Applicable

Recruiting

• Conditions: Colitis; Kidney Cancer; Diarrhea; Malignant Melanoma
• Interventions: Procedure: Faecal Microbiota Transplantation (FMT); Procedure: Placebo

• Registration Number: NCT06206707
• Lead Sponsor: University of Aarhus

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

Study Timeline

• Status Verified: 2023-12
• Study First Submitted: 2024-01-02
• Study First Submitted QC: 2024-01-04
• Study First Posted: 2024-01-16
• Study Start: 2024-01-23
• Last Update Submitted: 2024-01-24
• Last Update Posted: 2024-01-25
• Primary Completion: 2024-12-31
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Faecal microbiota transplantation (FMT)	Faecal Microbiota Transplantation (FMT)	Patients receive two applications of capsule FMT with 3-7 days between applications.
Placebo	Placebo	Patients receive two applications of placebo capsules with 3-7 days between applications.

Primary Outcome Measures

Name	Time	Method
Clinical remission of immune-mediated diarrhea	At 42 days after intervention treatment	Number of patients with steroid-free resolution of diarrhea, defined as \< 3 liquid stools (Bristol \<6) per 24 hours during day 40 and 41 after the last intervention treatment.

Secondary Outcome Measures

Name	Time	Method
Accumulated steroid dose	Up to 12 weeks after intervention treatment	Accumulated steroid dose (total dose in mg) during 12 weeks following experimental treatment.
Remission of diarrhea defined by CTCAE	At 42 days after intervention treatment	Number of patients in steroid-free clinical remission of diarrhea 6 weeks (42 days) after the last intervention treatment. Clinical remission is defined as \< 4 stools over baseline per day (CTCAE diarrhea grade 1 or less), at day 40 and 41.
Faecal-calprotectin	Up to 6 weeks after intervention treatment	Percentual change in faecal-calprotectin from prior to intervention to week 6 after the last intervention.
Endoscopic remission	Up to 6 weeks after intervention treatment	Endoscopic remission, defined as Mayo endoscopic score 0, at week 6 after the last intervention treatment.
Remission of colitis defined by CTCAE	At 42 days after intervention treatment	Number of patients in steroid-free clinical remission of colitis 6 weeks (42 days) after the last intervention treatment. Clinical remission is defined as asymptomatic in regards to colitis (CTCAE colitis grade 1 or less), at day 40 and 41.
Number of days until CTCAE diarrhea grade 1	Up to 12 weeks after intervention treatment	Number of days until less than 4 stools over baseline per day (CTCAE diarrhea grade 1 or less), lasting a minimum of 48 consecutive hours with no increase in steroid dose in the 12 weeks of follow-up.
Gut mucosa-associated microbiome	Up to 6 weeks after intervention treatment	Changes in mucosa-associated microbiome from baseline to week 6 after the last intervention.
Therapy response of FMT	Up to 12 weeks after intervention treatment	Therapy response defined as a decrease of at least 3 points in Simple Clinical Colitis Activity Index (SCCAI) score, at weeks 1, 6 and 12 after the last intervention treatment.
Faecal microbiota composition	Up to 6 weeks after intervention treatment	Changes in faecal microbiome composition from baseline to week 6 after the last intervention.
Resumption of immune checkpoint inhibitor therapy	Up to 12 weeks after intervention treatment	Number of patients resuming immune checkpoint inhibitor therapy during the 12 weeks of follow-up.
Endoscopic response	Up to 6 weeks after intervention treatment	Endoscopic response, defined as decrease in Mayo endoscopic score ≥1 grade, at week 6 after the last intervention treatment.
Number of days until resolution of diarrhea	Up to 12 weeks after intervention treatment	Number of days until resolution of diarrhea, defined as 3 or fewer Bristol type 6-7 stools per day, lasting a minimum of 48 consecutive hours.
Incidence of fecal microbiota transplantation (FMT)-related adverse events	At 42 days after intervention treatment	Number of adverse events (AE) during first 6 weeks after intervention treatment. AE's will be graded by CTCAE.
Incidence of fecal microbiota transplantation (FMT)-related serious adverse events	At 12 weeks after intervention treatment	Number of serious adverse events (SAE) during 12 weeks follow-up after the final intervention treatment. SAE's will be graded by CTCAE.
Hospitalisation	Up to 12 weeks after intervention treatment	Hospitalisation defined as the total number of days hospitalised, during 12 weeks of follow-up.
Blood immunological parameters	Up to 6 weeks after intervention treatment	Changes in blood immunological parameters (including circulating cytokines) from baseline and at week 6 after the last intervention.
Mortality	Up to 12 weeks after intervention treatment	Mortality during the 12 weeks of follow-up.
Response to immune checkpoint inhibitor therapy	Up to 12 weeks after intervention treatment	Response to immune checkpoint inhibitor therapy defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1 and iRECIST).
Patient and physician perceptions of FMT treatment	At 42 days after intervention treatment	Patient and physician perceptions of FMT treatment and the usage for IMC assessed by a patient questionnaire at week 6 and a physician questionnaire.
Health-related quality of life	At 42 days after intervention treatment	Changes in health-related quality of life assessed by EQ-5D-5L at baseline and week 6.
Colectomy	Up to 12 weeks after intervention treatment	Colectomy during 12 weeks of follow-up.

Trial Locations

Locations (1)

Aarhus University Hospital; 🇩🇰 Aarhus N, Denmark