FMT in Checkpoint Inhibitor-mediated Diarrhea and Colitis

Kidney Cancer Clinical Trial

— Immunobiome  

Official title:

Faecal Microbiota Transplantation for Immune Checkpoint Inhibitor-mediated Diarrhea/Colitis: a Randomised, Double-blind Pilot Efficacy and Safety Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06206707
• Other study ID #: 1-10-72-105-23
• Status: Recruiting
• Phase: N/A
• Start date: January 23, 2024
• Est. completion date: March 31, 2025

Study information

• Verified date: December 2023
• Source: University of Aarhus
• Contact: Trine L Laursen, BSc
• Phone: +4540408207
• Email: trnlau[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

As above

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Diarrhea
• Kidney Cancer
• Kidney Neoplasms
• Malignant Melanoma
• Melanoma

Intervention

Procedure:
• Faecal Microbiota Transplantation (FMT)
Capsule FMT
• Placebo
Placebo capsules

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus N

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical remission of immune-mediated diarrhea	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.	At 42 days after intervention treatment
Secondary	Remission of diarrhea defined by CTCAE	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.	At 42 days after intervention treatment
Secondary	Remission of colitis defined by CTCAE	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.	At 42 days after intervention treatment
Secondary	Therapy response of FMT	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.	Up to 12 weeks after intervention treatment
Secondary	Number of days until CTCAE diarrhea grade 1	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.	Up to 12 weeks after intervention treatment
Secondary	Number of days until resolution of diarrhea	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.	Up to 12 weeks after intervention treatment
Secondary	Incidence of fecal microbiota transplantation (FMT)-related adverse events	Number of adverse events (AE) during first 6 weeks after intervention treatment. AE's will be graded by CTCAE.	At 42 days after intervention treatment
Secondary	Incidence of fecal microbiota transplantation (FMT)-related serious adverse events	Number of serious adverse events (SAE) during 12 weeks follow-up after the final intervention treatment. SAE's will be graded by CTCAE.	At 12 weeks after intervention treatment
Secondary	Faecal microbiota composition	Changes in faecal microbiome composition from baseline to week 6 after the last intervention.	Up to 6 weeks after intervention treatment
Secondary	Gut mucosa-associated microbiome	Changes in mucosa-associated microbiome from baseline to week 6 after the last intervention.	Up to 6 weeks after intervention treatment
Secondary	Faecal-calprotectin	Percentual change in faecal-calprotectin from prior to intervention to week 6 after the last intervention.	Up to 6 weeks after intervention treatment
Secondary	Blood immunological parameters	Changes in blood immunological parameters (including circulating cytokines) from baseline and at week 6 after the last intervention.	Up to 6 weeks after intervention treatment
Secondary	Hospitalisation	Hospitalisation defined as the total number of days hospitalised, during 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Secondary	Colectomy	Colectomy during 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Secondary	Mortality	Mortality during the 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Secondary	Accumulated steroid dose	Accumulated steroid dose (total dose in mg) during 12 weeks following experimental treatment.	Up to 12 weeks after intervention treatment
Secondary	Resumption of immune checkpoint inhibitor therapy	Number of patients resuming immune checkpoint inhibitor therapy during the 12 weeks of follow-up.	Up to 12 weeks after intervention treatment
Secondary	Response to immune checkpoint inhibitor therapy	Response to immune checkpoint inhibitor therapy defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1 and iRECIST).	Up to 12 weeks after intervention treatment
Secondary	Patient and physician perceptions of FMT 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.	At 42 days after intervention treatment
Secondary	Health-related quality of life	Changes in health-related quality of life assessed by EQ-5D-5L at baseline and week 6.	At 42 days after intervention treatment
Secondary	Endoscopic response	Endoscopic response, defined as decrease in Mayo endoscopic score =1 grade, at week 6 after the last intervention treatment.	Up to 6 weeks after intervention treatment
Secondary	Endoscopic remission	Endoscopic remission, defined as Mayo endoscopic score 0, at week 6 after the last intervention treatment.	Up to 6 weeks after intervention treatment

External Links

•   Centre for faecal microbiota transplantation (CEFTA)