Colitis, Diarrhea, Kidney Cancer, Malignant Melanoma
Conditions
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
Interventions
Capsule FMT
PROCEDUREPlacebo
Placebo capsules
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a double-blind, placebo controlled, randomised trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Faecal microbiota composition | Up to 6 weeks after intervention treatment | Changes in faecal microbiome composition from baseline to week 6 after the last intervention. |
| 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. |
| 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. |
| 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. |
| 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. |
| Colectomy | Up to 12 weeks after intervention treatment | Colectomy during 12 weeks of follow-up. |
| Mortality | Up to 12 weeks after intervention treatment | Mortality during the 12 weeks of follow-up. |
| Accumulated steroid dose | Up to 12 weeks after intervention treatment | Accumulated steroid dose (total dose in mg) during 12 weeks following experimental treatment. |
| 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. |
| 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. |
| 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. |
| 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. |
| Hospitalisation | Up to 12 weeks after intervention treatment | Hospitalisation defined as the total number of days hospitalised, during 12 weeks of follow-up. |
Countries
Denmark
Contacts
Primary ContactTrine L Laursen, BSc
Backup ContactChristian L Hvas, PhD
Outcome results
None listed