Neoplasms

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Carcinoma

Carcinoma, Squamous Cell

Facies

Skin Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Topical 1% sirolimus cream applied daily to the face for 6 months

Topical placebo cream applied daily to the face for 6 months

The intervention topical cream consists of sirolimus 1% in a vehicle. Patients randomised to the intervention will be required to apply the sirolimus topical cream to their face for 6 months

Sirolimus Topical Cream

Cream containing only the base, or vehicle.

Placebo

Melanoma and Skin Cancer Trials Coordinator

Kiarash Khosrotehrani

Diona Damian

Angela Webster

Susan Brown

Daniel Chambers

Lea Dousset

Helmut Schaider

Sarah Chivers

Alvin Chong

Kiarash Khosrotehrani, MD PhD FACD

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 6 months in solid organ transplant recipients.

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 6 months. 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.

Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days (168 hours) prior to their baseline \& screening visit (D0) and agree to use adequate methods of contraception for the duration of drug administration.

Topical Sirolimus in Chemoprevention of Facial Squamous Cell Carcinomas in Solid Organ Transplant Recipients (SiroSkin)

A Randomised Double-blind Placebo-controlled Trial of Topical Sirolimus in Chemoprevention of Facial Squamous Cell Carcinomas in Solid Organ Transplant Recipients

The percentage of patients who develop keratinocyte carcinomas on the treated area at completion of 6 months of topical 1% sirolimus, then at 12 and 24 months follow up.

The percentage of patients who develop biopsy-proven SCC on the treated area at the completion of 6 months of topical 1% sirolimus, then at 12 and 24 months follow up.

The occurrence of biopsy-proven SCC at the completion of 6 months of topical 1% sirolimus, then at 12 and 24 months follow up on the treated area.

The percentage of patients who develop intraepidermal carcinomas (IECs), BCCs and subtypes of SCCs or BCCs at each of the aforementioned time-points on the treated area.

The occurrence of intraepidermal carcinomas (IECs), BCCs and subtypes of SCCs or BCCs at each of the aforementioned time-points on the treated area.

The percentage of patients who experience a reduction in the number of facial actinic keratosis from recruitment to the end of the study (6 months) on photographic images and counts.

The cost-effectiveness of utilizing topical sirolimus therapy on SOTRs measured by the ratio of the cost of the intervention to the improvement in the primary outcome.

Number and occurrence of intervention-related side effects, by type

The average number of doses of topical sirolimus (or placebo for the placebo arm) applied during the 24 weeks.

The percentage of patients who complete the 24-week course of treatment.

The percentage of patients who complete the 24-week course of treatment.

The percentage of patients who complete the 24-week course of treatment

Monash University

The University of Queensland

Melanoma and Skin Cancer Trials Limited

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Blood and Lymph Conditions

COVID-19

Autoimmune Diseases

Hematologic Neoplasms

Hematologic Diseases

Antibodies

Vaccines

Immunoglobulins

Myeloma Proteins

Paraproteins

Patients who have received a solid organ transplant and who have received at least 3 doses of Covid-19 vaccine

Patients with a rare autoimmune disease who have received at least 3 doses of Covid-19 vaccine

Patients with acute myeloid and lymphoid blood cancers who have received at least 3 doses of Covid-19 vaccine.

The lateral flow device to be used is the Fortress COVID-19 Total Antibody Device for the detection of IgM and IgG SARS-CoV-2 against the spike protein. The device has been evaluated for use in detecting anti-S in transplant patients and found to have a sensitivity of 92% and specificity of 95%.

self-administered lateral flow assays

Michelle Willicombe, MBBS, MD

DESIGN Observational epidemiological study

AIMS - To determine:

1. The proportion of immunosuppressed people who have detectable SARS-CoV-2 antibodies following a primary vaccine course (3 doses), and the demographic, disease, and treatment characteristics that influence antibody status.
2. If the detection of antibodies inversely correlates with subsequent risk of severe acute respiratory syndrome coronavirus-2 infection and/or severity of disease in immunosuppressed people.

The aim of this proposal is to assess at a population level; 1) the proportion of immunosuppressed people who have detectable SARS-CoV-2 antibodies following a primary vaccine course (3 doses), and the sociodemographic, disease, and treatment characteristics that influence antibody status; 2) if the detection of antibodies inversely correlates with subsequent risk of SARS-CoV2 infection and/or severity of disease in immunosuppressed individuals.

The investigators aim to target patient groups least likely to mount an immune response to vaccination; a) solid organ transplant recipients; b) patients with a rare autoimmune disease c) patients with haematological malignancies, specifically lymphoid malignancies. The investigators will use comprehensive registries to identify and recruit patients from these groups, and utilise the existing linkages these registries already have to obtain COVID-19 outcome information.

The investigators hypothesise that a sizeable proportion of immunosuppressed people will have no detectable SARS-CoV-2 antibodies following a three vaccine doses, and that this cohort is particularly susceptible to SARS-CoV-2 infection and death.

Mass Evaluation of Lateral Flow Immunoassays for the Detection of SARS-CoV-2 (Covid-19) Antibodies

Mass Evaluation of Lateral Flow Immunoassays for the Detection of SARS-CoV-2 Antibody Responses in Immunosuppressed People (The MELODY Study)

1. The proportion of with and without antibodies to SARS-CoV-2 at 21 - 90 days post three vaccine doses will be presented.

1. The proportion of with and without antibodies to SARS-CoV-2 at 21 - 90 days post four vaccine doses will be presented.

The incidence of participants having at least one RT-qPCR proven infection in the 6-month follow-up will be presented for those with and without antibodies to SARS-CoV-2 after 3rd or 4th vaccine.

Incidence of participants hospitalised due to COVID-19 and deaths due to COVID-19 by 6 months will be presented for those with and without antibodies to SARS-CoV-2 following 3rd or 4th vaccine, and compared as described above if there are sufficient events.

Rates of those with and without antibodies to SARS-CoV-2 after 3rd or 4th vaccine will be presented for different clinical characteristics and sociodemographic factors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Topical Sirolimus in Chemoprevention of Facial Squamous Cell Carcinomas in Solid Organ Transplant Recipients (SiroSkin)	NCT05860881	Solid Organ Tra... Skin Cancer	Sirolimus Topic... Placebo	18 Years -	Melanoma and Skin Cancer Trials Limited
Topical Sirolimus in Chemoprevention of Facial Squamous Cell Carcinomas in Solid Organ Transplant Recipients (SiroSkin)	NCT05860881	Solid Organ Tra... Skin Cancer	Sirolimus Topic... Placebo	18 Years -	Melanoma and Skin Cancer Trials Limited
Mass Evaluation of Lateral Flow Immunoassays for the Detection of SARS-CoV-2 (Covid-19) Antibodies	NCT05148806	Solid Organ Tra... Autoimmune Dise... Haematological ...	self-administer...	12 Years -	Imperial College London
Topical Sirolimus in Chemoprevention of Facial Squamous Cell Carcinomas in Solid Organ Transplant Recipients (SiroSkin)	NCT05860881	Solid Organ Tra... Skin Cancer	Sirolimus Topic... Placebo	18 Years -	Melanoma and Skin Cancer Trials Limited
Mass Evaluation of Lateral Flow Immunoassays for the Detection of SARS-CoV-2 (Covid-19) Antibodies	NCT05148806	Solid Organ Tra... Autoimmune Dise... Haematological ...	self-administer...	12 Years -	Imperial College London

Spots Global Cancer Trial Database for solid organ transplant recipients