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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001137381
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
10/07/2026
Date registered
Help: Date registered
11/09/2026
Date last updated
Help: Date last updated
11/09/2026
Date data sharing statement initially provided
Help: Data sharing statement date
11/09/2026
Type of registration
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Prospectively registered

Titles & IDs
Public title
Faecal Microbiota Transplantation Optimised Immune Checkpoint Inhibitor Therapy in Advanced Cutaneous Squamous Cell Carcinoma
Scientific title
Faecal Microbiota Transplantation Optimised Immune Checkpoint Inhibitor Therapy in Advanced Cutaneous Squamous Cell Carcinoma
Additional trial identifiers [1] 317806 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
FITE Study
Related trial records

Health condition
Health condition(s) studied:
Advanced Cutaneous Squamous Cell Carcinoma 342722 0
Condition category
Condition code
Cancer 338875 338875 0 0
Non melanoma skin cancer
Skin 339018 339018 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Faecal Microbiota Transplant (FMT) Intervention
Participants receive two colonoscopic Faecal Microbiota Transplant administrations of anaerobically prepared whole-stool supplied by BiomeBank (Adelaide, Australia), a Good Manufacturing Practice (GMP)-certified Therapeutic Goods Administration (TGA) -approved stool bank:

Dose: 37.5g (150ml) per administration
Schedule: FMT #1 within 7 days of first cemiplimab dose; FMT #2 at 6 weeks after FMT #1
Mode of administration: Colonoscopic infusion into the ileum or right colon, performed by a credentialled gastroenterologist at St Vincent's Hospital Melbourne
Duration: Two administrations over 6 weeks
Participants are allocated to either a single-donor (2 doses of FMT both obtained from a single individual; Cohort A) or two-donor (2 doses of FMT obtained from two different individuals; Cohort B) FMT formulation. Standard bowel preparation (Prepkit-C) is performed prior to each colonoscopy. Loperamide 4mg orally is administered 2 hours before each procedure to assist retention. FMT will be administed by study investigators, and adherence monitored.

The FMT product is a biological therapeutic good holding TGA approval for recurrent Clostridioides difficile infection.

Cemiplimab (International Nonproprietary Name {INN}: cemiplimab)
Cemiplimab is a fully human anti-PD-1 IgG4 monoclonal antibody administered as standard-of-care PBS-reimbursed therapy concurrently with FMT:

Dose: 350mg flat dose
Mode of administration: Intravenous infusion over approximately 30 minutes
Schedule: Every 3 weeks after first dose; with the FMT being administred within 7 days of the first dose of cemiplimab
Duration: Up to 24 months, or until disease progression, unacceptable toxicity, or patient/clinician decision to cease
Cemiplimab may be administered at St Vincent's Hospital Melbourne or at a local oncology service for rural and regional participants.

Dietary Co-intervention
All participants will be counselled to follow the same whole-food, no-food-additive diet commencing 3 weeks prior to the first FMT and continuing for the duration of the study. The diet is plant-enriched, rich in fermentable fibres and polyphenols, moderate in animal protein, and low in saturated fat. Written dietary guidelines, a sample meal plan, and verbal counselling from a clinical dietitian are provided to each participant, with the participants to self prepare their food. The dietitian may adapt recommendations to accommodate individual food intolerances while maintaining the core dietary principles. Dietician review and adherence assessment via food records will occur at 3/6/12/24 months.

All participants in this study will receive the same intervention, the cohorts are assigned based on the availability of the FMT at the time of enrollment (convenience allocation).
Intervention code [1] 334657 0
Treatment: Drugs
Intervention code [2] 334658 0
Lifestyle
Intervention code [3] 334808 0
Treatment: Other
Description of the comparator or control
Primary Endpoint - No control group
Comaprator group for the cohort intervention (secondary endpoint) is single donor FMT.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 346087 0
Progression-free survival (PFS)
Timepoint [1] 346087 0
Progression-free survival (PFS), defined as the time from initiation of immunotherapy until objective disease progression or death from any cause, whichever occurs first. Standard care radiologic imaging will be performed approximately every 3 months and utilized to assess RECIST v1.1, or if imaging is not completed then WHO clinical response criteria may be used for participants assessed clinically (e.g., predominantly cutaneous disease).
Secondary outcome [1] 464543 0
Overall Response Rate (ORR)
Timepoint [1] 464543 0
From treatment initiation to disease progression or end of study (up to 24 months)
Secondary outcome [2] 464544 0
Best Overall Response (BOR)
Timepoint [2] 464544 0
From treatment initiation to disease progression or end of study (up to 24 months)
Secondary outcome [3] 464545 0
Disease Control Rate (DCR)
Timepoint [3] 464545 0
From treatment initiation to disease progression or end of study (up to 24 months)
Secondary outcome [4] 464546 0
Progression-Free Survival Against an External Control Arm
Timepoint [4] 464546 0
Time from initiation of immunotherapy until objective disease progression or death from any cause
Secondary outcome [5] 464547 0
Overall Survival (OS)
Timepoint [5] 464547 0
From treatment initiation to death or end of follow-up (up to 10 years)
Secondary outcome [6] 464548 0
Disease-Specific Survival (DSS)
Timepoint [6] 464548 0
From treatment initiation to death from cSCC or end of follow-up (up to 10 years)
Secondary outcome [7] 464549 0
Duration of Response (DOR)
Timepoint [7] 464549 0
From first documented response to progression or death (up to 24 months)
Secondary outcome [8] 464550 0
Complete Response Rate
Timepoint [8] 464550 0
From treatment initiation to disease progression or end of study (up to 24 months)
Secondary outcome [9] 464551 0
Duration of Disease Control
Timepoint [9] 464551 0
From first documented disease control to progression or death (up to 24 months)
Secondary outcome [10] 464552 0
FMT Safety
Timepoint [10] 464552 0
From treatment initiation to end of active follow-up (24 months)
Secondary outcome [11] 464553 0
FMT Tolerability
Timepoint [11] 464553 0
From FMT #1 to end of active follow-up (24 months), at a minimum frequency of 3 monthly visits.
Secondary outcome [12] 464554 0
Donor Microbial Strain Engraftment
Timepoint [12] 464554 0
Pre-FMT, Month 3 and Month 12 post first FMT administration
Secondary outcome [13] 464555 0
Gut Microbiome Composition and Function, as a descriptive composite microbial assessment.
Timepoint [13] 464555 0
Screening, pre-FMT, Month 3 and Month 12 post first FMT administration
Secondary outcome [14] 464556 0
Skin Microbiome Composition differences between cancerous and non-cancerous skin.
Timepoint [14] 464556 0
Pre-FMT, Month 3 and Month 12 from first FMT administration.
Secondary outcome [15] 464557 0
Mucosal Microbiota
Timepoint [15] 464557 0
FMT #1 and FMT #2 visits
Secondary outcome [16] 464558 0
Changes in systemic immune cell populations and serum cytokine and complement profiles following FMT and ICI therapy. This will be assessed as a composite outcome.
Timepoint [16] 464558 0
Screening, pre-FMT, Month 3 and Month 12 from first FMT administration.
Secondary outcome [17] 467016 0
Assess response to single vs two donor dose strategy [scientific exploratory analysis only]
Timepoint [17] 467016 0
Screening, pre-FMT, Month 3 and Month 12 post first FMT administration

Eligibility
Key inclusion criteria
1. Age 18 years or older
2. Histologically confirmed locally advanced (not amenable to curative surgery and/or radiotherapy) or metastatic cutaneous squamous cell carcinoma (cSCC), including:
- SCC of unknown primary with unresectable nodal metastases and a prior cSCC lesion treated within the draining lymph node echelon
- SCC of unknown primary with a positive UV-mutational signature (COSMIC 7A/7B)
- Parotid SCC considered by the investigator to have arisen from a prior cutaneous lesion
3. Treatment-naïve for systemic anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy
4. ECOG performance status 0–2
5. Life expectancy of 6 months or greater
6. Willing and able to undergo colonoscopic FMT and comply with all study-related specimen collection procedures
7. Willing and able to provide written informed consent and comply with all clinic visits and study-related procedures
8. Able to understand and complete study-related questionnaires
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
1. SCC arising in a non-cutaneous site (including oral cavity, oropharynx, paranasal sinus, larynx, hypopharynx, nasopharynx, salivary gland, nasal mucosa, or anogenital area)
2. Pregnancy, intention to become pregnant within 12 months, or breastfeeding
3. History of allogeneic stem cell transplant or solid organ transplantation (corneal transplants are permitted)
4. Severe allergy or anaphylaxis to food products
5. Total white cell count less than 3.0 × 10E9/L or albumin less than 20g/L
6. Concurrent solid organ malignancy other than localised cSCC, or history of malignancy other than localised cSCC within 3 years of enrolment, with the exception of tumours with negligible risk of metastasis or death (including adequately treated basal cell carcinoma, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or low-risk early-stage prostate adenocarcinoma under active surveillance)
7. Immunosuppressive corticosteroids greater than 10mg prednisone daily (or equivalent) within 14 days prior to first dose, or other systemic immunosuppressants
8. Prior systemic anti-cancer immunotherapy for cSCC including anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-4-1BB, anti-OX-40, therapeutic vaccines, or PI3Kd inhibitors
9. Uncontrolled HIV, hepatitis B, or hepatitis C infection (controlled infections meeting specified criteria are permitted — refer to full protocol for details)
10. Active tuberculosis
11. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrolment
12. History of documented allergic reaction or acute hypersensitivity to antibody treatments, or known hypersensitivity to any excipient in the cemiplimab drug product
13. Any medical comorbidity, physical finding, metabolic dysfunction, or laboratory abnormality that in the opinion of the investigator renders the participant unsuitable for participation due to safety risk or potential to affect interpretation of results
14. Known psychiatric or substance abuse disorder that would interfere with study participation requirements
15. Any condition that the treating clinician considers to pose a risk to the participant in undertaking FMT

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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
A sample size of approximatley 30 participants was determined via Monte Carlo simulation of 100,000 replicates. This provides 82% power to detect a clinically meaningful improvement in progression-free survival (PFS), defined as 74% PFS at 12 months, against a fixed null PFS rate of 55% at 12 months at the 0.05 significance level using a one-sample log-rank test assuming constant hazards. The null PFS rate of 55% is derived from the registrational cemiplimab phase II trial in advanced cSCC (DOI: 10.1136/jitc-2021-002757). Simulation assumptions include recruitment at a constant rate averaging 3 participants per month (Poisson process), trial closure to recruitment at target sample size or 12 months whichever is later, final data cutoff at 36 months, and loss to follow-up at a constant hazard averaging 1% every 3 years.

Baseline demographics, treatment and response data will be summarised using descriptive statistics. The influence of selected clinicopathological prognostic features on survival outcomes will be assessed using Cox regression (covariates: age, sex, head and neck primary site, ECOG performance status, immunocompromised status, metastatic disease and prior nodal radiotherapy), with Firth's penalised likelihood applied in the event of data separation given the small sample size. Survival will be estimated using the Kaplan–Meier method with 95% confidence limits estimated using the beta product confidence procedure. Microbial, immunological and metabolomic data will be analysed by experienced bioinformaticians using standard pipelines for shotgun metagenomic sequencing, metabolomics and immune profiling, with comparison between responders and non-responders using descriptive and exploratory statistical methods.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
21/09/2026
Actual
Date of last participant enrolment
Anticipated
21/09/2027
Actual
Date of last data collection
Anticipated
21/09/2037
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 322354 0
Hospital
Name [1] 322354 0
St Vincent's Hospital, Melbourne
Country [1] 322354 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital, Melbourne
Address
Country
Australia
Secondary sponsor category [1] 325271 0
None
Name [1] 325271 0
Address [1] 325271 0
Country [1] 325271 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 320854 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 320854 0
Ethics committee country [1] 320854 0
Australia
Date submitted for ethics approval [1] 320854 0
31/07/2026
Approval date [1] 320854 0
02/09/2026
Ethics approval number [1] 320854 0
St Vincent’s HREC Reference: 255/26

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 151850 0
Dr Luke McLean
Address 151850 0
Department of Oncology, St Vincent's Hospital. Victoria Parade, Fitzroy VIC 3065
Country 151850 0
Australia
Phone 151850 0
+61 3 9231 3155
Fax 151850 0
Email 151850 0
[email protected]
Contact person for public queries
Name 151851 0
Luke McLean
Address 151851 0
Department of Oncology, St Vincent's Hospital. Victoria Parade, Fitzroy VIC 3065
Country 151851 0
Australia
Phone 151851 0
+61 3 9231 3155
Fax 151851 0
Email 151851 0
[email protected]
Contact person for scientific queries
Name 151852 0
Dr Amy Hamilton
Address 151852 0
Department of Gastroenterology, St Vincent's Hospital. Victoria Parade, Fitzroy VIC 3065
Country 151852 0
Australia
Phone 151852 0
+61 9231 2316
Fax 151852 0
Email 151852 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.