Clinical trial NCT05860881: Topical Sirolimus in Chemoprevention of Facial Squamous Cell Carcinomas in Solid Organ Transplant Recipients (SiroSkin)
Official title: A Randomised Double-blind Placebo-controlled Trial of Topical Sirolimus in Chemoprevention of Facial Squamous Cell Carcinomas in Solid Organ Transplant Recipients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Solid Organ Transplant Recipients
Skin Cancer
Lead sponsor: Melanoma and Skin Cancer Trials Limited
Sponsor class: OTHER
Collaborators: name: Monash University
name: The University of Queensland
First posted: 2023-05-16
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 01.21 SiroSkin is a phase 3, double-blind, multi-centre, parallel-arm, randomised, placebo-controlled trial to evaluate the use of topical 1% sirolimus in the chemoprevention of skin cancer, versus placebo, applied every night for 24 weeks in solid organ transplant recipients.

Detailed description: Keratinocyte carcinomas are a major burden affecting mortality and morbidity in solid organ transplant recipients (SOTRs). Due to an increased prevalence of skin cancers, SOTRs require recurrent skin checks and frequent skin cancer surgery. The gold standard of treatment is surgery, enabling complete remission and a cure in the majority of cases. Despite this, there is no effective way of preventing new cancers from developing in the same area.

Oral sirolimus is a selective immunosuppressant agent which has proven to reduce the burden of skin cancer; however, it is poorly tolerated due to side effects. Topical sirolimus has proven effective in reducing the skin cancer burden in animal models and is safe on the face of patients with tuberous sclerosis. An initial 12-week phase II clinical trial recently conducted by the research team suggested topical sirolimus to be safe and effective, as it reduced the early signs of skin cancer without any major side effects.

In this phase III randomised, double-blind, placebo-controlled study, we propose using 1% topical sirolimus applied to the face on a regular basis for 24 weeks. We aim to determine whether this topical cream can fill a major gap in our current therapies by reducing the onset of new skin cancers and therefore reduce the burden of disease in terms of number of biopsies and surgeries, and potential hospitalisations and death.

Eligibility criteria: Inclusion Criteria:

1. Be aged 18 years or older and able to provide consent
2. Have received an organ transplant equal to or greater than 12 months prior to consent
3. Have had at least 1 SCC/BCC in the past 5 years
4. Have at least 5 keratotic lesions on their face at inclusion

Exclusion Criteria:

1. Are currently receiving sirolimus or everolimus orally\*
2. Have a skin cancer on their face requiring excisional surgery\*\*
3. Have an open wound on their face requiring treatment
4. Are pregnant or planning to become pregnant in the next 6 months
5. Anticipate elective medical events which may prevent daily cream application.
6. Are unable to provide informed consent, complete questionnaires and attend trial site for visits
7. Are participating in another clinical trial with an investigational drug/device aiming to reduce skin cancers or affect level of immunosuppression
8. Planning to move overseas within 2 years

(\*)Patients are eligible to join the study after ceasing treatment and after a washout period of 16 days for sirolimus and 8 days for everolimus.

(\*\*) Once treatment of the lesion is completed these patients can be re-screened.

Primary outcomes:
measure: KC development
timeFrame: 2 years
Secondary outcomes:
measure: The occurrence of KCs
timeFrame: 2 years
measure: The number of biopsy-proven SCCs
timeFrame: 2 years
measure: The occurrence of biopsy-proven squamous cell carcinomas (SCCs)
timeFrame: 2 years
measure: The number of IECs, BCCs and subtypes of SCCs or BCCs
timeFrame: 2 years
measure: The occurrence of IECs, BCCs and subtypes of SCCs or BCCs
timeFrame: 2 years
measure: The number of AKs
timeFrame: 2 years
measure: Cost-effectiveness
timeFrame: 2 years
measure: The number and occurrence of intervention-related side effects
timeFrame: Up to 30 days post end of treatment
measure: Compliance
timeFrame: 6 months
measure: Quality of life (EQ-5D-5L)
timeFrame: 2 years
measure: Quality of life (BaSQoL)
timeFrame: 2 years
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Carlton
country: Australia
facility: Skin Health Institute
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
Study officials:
affiliation: The University of Queensland
name: Kiarash Khosrotehrani, MD PhD FACD
role: STUDY_CHAIR
References: