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Trial registered on ANZCTR


Registration number
ACTRN12624000120572
Ethics application status
Approved
Date submitted
11/01/2024
Date registered
9/02/2024
Date last updated
25/08/2024
Date data sharing statement initially provided
9/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study of the Efficacy and Safety of Faecal Microbiota Transplant for the Treatment of Immune Checkpoint Inhibitor Colitis
Scientific title
A Pilot Study of the Efficacy and Safety of Faecal Microbiota Transplant for the Treatment of Immune Checkpoint Inhibitor Colitis
Secondary ID [1] 311245 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune Checkpoint Inhibitor Colitis 332467 0
Condition category
Condition code
Inflammatory and Immune System 329161 329161 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 329162 329162 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 329414 329414 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be an open-label study, all potential participants will be offered the intervention.

Faecal Microbiota Transplant (FMT) - provided by The Australian Red Cross Lifeblood

A suspension of faecal microbiota derived from 50g of human stool from an individual screened donor in a mixture of Glycerolyte-57 and normal saline, to achieve an equivalent concentration of 10% glycerol as a cryoprotectant. The suspension is filtered to remove particles >1mm.

Faecal Microbiota for Transplant (Faecal microbiota cryopreserved in glycerol) – is designed for administration to the patient’s caecum via colonoscopy as a single 150g dose.

The procedure including both colonoscopy and faecal transplant will be performed by a consultant gastroenterologist and will take approximately 30 minutes.

This will be administered once only on Day 0 of the study.
Intervention code [1] 327703 0
Treatment: Other
Comparator / control treatment
Patients who do not wish to have an FMT will be enrolled on to the control arm of the study and be managed as per standard of care for immune checkpoint inhibitor colitis with steroid therapy only. As per standard of care, patients who fail to respond to steroid therapy may receive biologic therapy including infliximab or vedolizumab.
Control group
Active

Outcomes
Primary outcome [1] 336990 0
Commencement of steroid therapy
Timepoint [1] 336990 0
Patients in the FMT intervention arm will be assessed up to day 7 post-transplant. Patients in the control group will be assessed up to day 7 post commencement of steroid therapy.
Secondary outcome [1] 430333 0
Change in endoscopic grading of colitis
Timepoint [1] 430333 0
Patients in the FMT intervention arm and control group will be assessed at week 8 post the initial colonoscopy
Secondary outcome [2] 430334 0
Change in histologic grading of colitis
Timepoint [2] 430334 0
Patients in the FMT intervention arm and control group will be assessed at week 8 post the initial colonoscopy
Secondary outcome [3] 430335 0
Rate of less than or equal to Grade 1 diarrhoea and/or colitis
Timepoint [3] 430335 0
Patients in the FMT intervention arm and control group will be assessed at week 8 post the initial colonoscopy
Secondary outcome [4] 431130 0
Safety of FMT. Possible adverse events include worsening of clinical symptoms including diarrhoea, abdominal pain, rectal bleeding and bloating.
Timepoint [4] 431130 0
Patients in the FMT intervention arm and control group will be assessed at week 8 post the initial colonoscopy

Eligibility
Key inclusion criteria
- 18 years of age or older.
- Able to provide informed consent.
- Receipt of an immune checkpoint inhibitor agent (e.g. anti-CTLA-4, anti-PD-(L)1) as part of a treatment regimen for a solid cancer within 6 months of the onset of colitis symptoms. The ICI may be used as a single agent, or in combination with other ICIs, or with chemotherapy.
- Current diagnosis of immune-related diarrhoea and/or colitis characterized by grade 2 diarrhea as per CTCAE v5.0.
- Treatment including corticosteroid and biologic naive
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients who have received either corticosteroid or immunosuppressive treatment for the current episode of ICI colitis
- Life-threatening food allergies, e.g. nut allergy
- Patients unable to provide informed consent
- Patients with a known diagnosis of inflammatory bowel disease
- Patients with a previous total colectomy
- Patients with an –ostomy (i.e. ileostomy or colostomy)
- Diagnosis of a thromboembolic event (deep vein thrombosis, pulmonary embolism, embolic stroke, myocardial infarction, or peripheral arterial insufficiency) within 3 months of enrollment.
- Diagnosis of concomitant infectious colitis (e.g. C. difficile or other bacterial source), unless the patient has finished an appropriate length of treatment with antibiotics as indicated for each diagnosis at the time of enrollment.
- Active pregnancy or breastfeeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/06/2024
Actual
5/06/2024
Date of last participant enrolment
Anticipated
2/06/2025
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 315503 0
Other
Name [1] 315503 0
Gastroenterological Society of Australia Research Grant
Country [1] 315503 0
Australia
Primary sponsor type
University
Name
Monash University
Address
21 Chancellor's Walk, Monash University, Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 317580 0
None
Name [1] 317580 0
Address [1] 317580 0
Country [1] 317580 0
Other collaborator category [1] 282906 0
Hospital
Name [1] 282906 0
Alfred Health
Address [1] 282906 0
55 Commercial Road, Melbourne Victoria 3004
Country [1] 282906 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314405 0
Alfred Health Ethics and Research Committee
Ethics committee address [1] 314405 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 314405 0
Australia
Date submitted for ethics approval [1] 314405 0
14/09/2023
Approval date [1] 314405 0
06/12/2023
Ethics approval number [1] 314405 0

Summary
Brief summary
The immune checkpoint inhibitors (ICI) are a form of cancer treatment that have resulted in significant improvement in the outcomes of the management of a number of malignancies. They work by activating the immune system and thereby promoting the destruction of cancer cells. The use of ICIs is limited by a group of side-effects known as immune related adverse events (irAEs). One of the more common irAEs is the development of inflammation of the large intestine known as ICI colitis. The treatment of ICI colitis is mostly aimed at suppressing the immune system and ‘switching off’ the overactive immune cells that are causing the inflammation. The use of treatments that suppress the Immune system may themselves result in significant side-effects by increasing the risk of infection. Immune suppression may have a detrimental impact on the outcome of the cancer being treated, by reducing the ability of the patient’s immune system to control the cancer.

Who is it for?
You may be eligible for this study if you are an adult who is receiving treatment for a solid cancer, who has experienced onset of colitis symptoms within 6 months of treatment commencement.

Study details
Participants in this study will be able to choose if they wish to receive the intervention or are considered part of the 'control' group. Participants who choose to receive the intervention will undergo a colonoscopy where they will receive a faecal transplant.
If a participant chooses not to receive the intervention, they will continue with standard treatment as determined by their doctor.
All participants will then be followed up for 8 weeks and asked to complete questionnaires and provide additional blood and stool samples.

It is hoped that this study will help assess the efficacy and safety of Faecal Microbiota Transplant as first-line therapy in the treatment of ICI colitis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131466 0
Prof Alex Boussioutas
Address 131466 0
Alfred Hospital. 55 Commercial Road. Melbourne. 3004
Country 131466 0
Australia
Phone 131466 0
+61 3 9903 8942
Fax 131466 0
Email 131466 0
[email protected]
Contact person for public queries
Name 131467 0
Alex Boussioutas
Address 131467 0
Alfred Hospital. 55 Commercial Road. Melbourne. 3004
Country 131467 0
Australia
Phone 131467 0
+61 3 9903 8942
Fax 131467 0
Email 131467 0
[email protected]
Contact person for scientific queries
Name 131468 0
Alex Boussioutas
Address 131468 0
Alfred Hospital 55 Commercial Road. Melbourne. 3004
Country 131468 0
Australia
Phone 131468 0
+61 3 9903 8942
Fax 131468 0
Email 131468 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.