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Trial registered on ANZCTR


Registration number
ACTRN12622001585718
Ethics application status
Approved
Date submitted
15/12/2022
Date registered
22/12/2022
Date last updated
5/10/2024
Date data sharing statement initially provided
22/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The ROSEND Trial - A Randomised trial for the treatment of recalcitrant symptomatic rosacea using definitive volumetric modulated arc radiotherapy or standard dermatological treatment
Scientific title
Phase IIb open label randomised controlled trial of definitive volumetric modulated arc radiotherapy versus standard dermatological treatment for recalcitrant symptomatic rosacea
Secondary ID [1] 308007 0
Nil
Universal Trial Number (UTN)
U1111-1282-7725
Trial acronym
ROSEND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recalcitrant Rosacea 328151 0
Condition category
Condition code
Skin 325205 325205 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ARM B: Volumetric Modulated Arc Therapy (VMAT): 36Gy in 20 once daily fractions delivered within a period of eight weeks in total inclusive of a mid-treatment break of a minimum two weeks.
Patients are required to attend a treatment planning session that will assist with planning the treatment. The planning procedure will take up to approximately 60 minutes and involve a computed-tomography (CT) scan with the patient positioned in the treatment position.
Treatment is expected to take around 15 minutes per treatment. The intervention will be prescribed by a radiation oncologist and administered by radiation therapists. Patients will commence treatment within four (4) weeks or randomisation and there will be approximately one (1) to two (2) weeks from the time of simulation to the commencement of radiotherapy.
During treatment, imaging will be completed to ensure treatment is administered accurately.
All patients will complete quality of life.
Intervention code [1] 324809 0
Treatment: Other
Comparator / control treatment
The comparator/control treatment for this study is the standard of care dermatological arm - treatment will be one or a combination of the standard dermatological treatments.
The aim is to determine if interventional arm is superior to the comparator/control treatment.
ARM A: A course of standard-of-care dermatological treatment, or a combination of treatments at the discretion of the treating Dermatologist, which will involve; topical therapy applied for a minimum of 16 weeks to a maximum of indefinitely during the study period (Metronidazole (0.75%) gel or cream, applied once or twice daily or Ivermectin (1%) cream applied once daily), and/or Vascular laser or Intense pulse light treatment delivered by a Dermatologist – limited to three episodes of treatment of approximately 15-20 minutes duration each, with a maximum of four weeks between each episode, and/or Oral antibiotic therapy (Doxycycline 50-100 mg per day or Minocycline 50-200 mg per day) taken for a minimum of eight weeks to a maximum of indefinitely during the study period.
All patients will complete quality of life and a medication diary.
If in-field failure occurs, crossover from the control arm to the intervention arm will be permitted which will be optional and at the discretion of the investigator. A patient will be eligible to crossover if they experience in-field failure, are willing to cease any other current therapy for recalcitrant rosacea and provide written informed consent to cross-over to receive VMAT radiotherapy. Patients who have in-field failure and cross-over after the 12 month timepoint may undergo a biopsy if the 12-month biopsy was negative for rosacea.
There will be a washout period of 8 weeks between ceasing standard-of-care treatment and commencing VMAT.
Control group
Active

Outcomes
Primary outcome [1] 333042 0
Evaluate the efficacy of VMAT compared to the dermatological standard of care at 12 months post-randomisation measured by a the incidence of in-field failure within 12 months of randomisation. This will be assessed through use of the Investigator global assessment (IGA) scale for Rosacea. Failure is defined as a subsequent increase to an IGA score of 2 or higher following initial clearance of significant rosacea or patients who do not have any clearance of significant rosacea within 12 months.
Timepoint [1] 333042 0
Assessed 12 months following date of randomisation.
Secondary outcome [1] 416854 0
Proportion of patients with in-field failure. This will be assessed through use of the Investigator global assessment (IGA) scale for Rosacea. Failure is defined as a subsequent increase to an IGA score of 2 or higher following initial clearance of significant rosacea or patients who do not have any clearance of significant rosacea within 12 months.
Timepoint [1] 416854 0
Assessed 12 months post randomisation.
Secondary outcome [2] 416855 0
Cumulative incidence of treatment-related acute toxicity as graded by the CTCAE v5. Analysis of Adverse Events (AEs) will be based on the safety population (ie. only patients who received a study treatment), and patients will be grouped for analysis based on the treatment they actually received. Possible acute AEs for radiotherapy arm include dry desquamation of the skin, mucositis and mild epistaxis. For the standard of care arm, possible acute AEs includes Gastro-intestinal upset/nausea due to use of doxycycline, allergic reaction to metronidazole or ivermectin creams.
Timepoint [2] 416855 0
Reported within 6 months of treatment.
For patients receiving radiotherapy - assessed at baseline, end of radiotherapy, four weeks following end of radiotherapy, then three and 6 months from date of randomisation.
For those on the standard of care arm - assessed at baseline, then three and 6 months following randomisation.
Secondary outcome [3] 416856 0
Cumulative incidence of treatment-related late toxicity as graded by the CTCAE v5. Analysis of AEs will be based on the safety population (ie. only patients who received a study treatment), and patients will be grouped for analysis based on the treatment they actually received. A possible late AE for the radiotherapy arm is telangiectasia . For the standard of care arm, a possible late AE is scarring or pigmentation of skin following laser or light treatment..
Timepoint [3] 416856 0
Reported greater than 6 months following treatment.
For patients receiving radiotherapy - assessed at 9, 12, 18 and 24 months from date of randomisation.
For those on the standard of care arm - assessed at 9, 12, 18 and 24 months from date of randomisation..
Secondary outcome [4] 416857 0
Patient-reported Quality of Life (QoL) assessed using the Dermatology Life Quality Index (DLQI). For general inflammatory skin conditions, a change in DLQI score of at least 4 points will be considered clinically important
Timepoint [4] 416857 0
For patients receiving radiotherapy - assessed at baseline, end of radiotherapy, 4 weeks following the end of radiotherapy then 3, 6, 9, 12, 18 and 24 months following randomisation.
For those on the standard of care arm - assessed at baseline, and then at 3, 6, 9, 12, 18 and 24 months following date of randomisation.
Secondary outcome [5] 416858 0
Change in patient-assessed erythema of rosacea score at relapse or 12- and 24- months compared to baseline, as measured by the Revised PSA–5 score of facial erythema of rosacea
Timepoint [5] 416858 0
Assessed at baseline, then 12, and 24 months following randomisation and time of relapse.
Secondary outcome [6] 416859 0
Proportion of patients requiring further therapy for rosacea by 12- and 24- months (VMAT, topical creams or systemic treatments) through assessment of medical records or during a study visit..
Timepoint [6] 416859 0
Assessed 12, and 24 months following randomisation.
Secondary outcome [7] 416860 0
Proportion of patients with clearance of rosacea (a reduction in score from 2-4 (mild to severe) to 0-1 (clear to almost clear) using the IGA scale for rosacea following subsequent therapy.
Timepoint [7] 416860 0
Assessed 24 months post randomisation.
Secondary outcome [8] 416868 0
Incremental cost effectiveness of VMAT radiation therapy (RT) compared to standard of care, as measured by Quality Adjusted Life Years (QALYs). Costs will include initial and subsequent treatments (tracked by a patient diary), attendances with local physicians and specialists, and AE management. QoL will be evaluated using the EQ-5D-5L. Data will be collected by assessing patient medical records.
Timepoint [8] 416868 0
Assessed at baseline, during radiotherapy planning, end of radiotherapy, 4 weeks following end of radiotherapy then 3, 6, 9, 12, 18 and 24 months following randomisation.
Secondary outcome [9] 426315 0
Rate of per-protocol compliance to the VMAT RT planning and treatment protocol. Compliance data will be collected from the documented Radiation Therapy Quality Assurance assessment, with major and minor deviations defined in the trial protocol.
Timepoint [9] 426315 0
Assessed immediately after radiotherapy planning is completed and prior to treatment commencing.
Secondary outcome [10] 426316 0
Rate of per-protocol compliance to the prescribed standard of care treatment, assessed via a patient medication diary
Timepoint [10] 426316 0
Assessed at 3, 6, 9, 12, 18 and 24 months following randomisation.

Eligibility
Key inclusion criteria
60 years of age or over.
Recalcitrant and relapsing rosacea, defined as those who have suffered with rosacea for at least 10 years and have relapsed following treatment with at least one systemic therapy and one topical therapy. Prior therapy must have been administered for at least 12 weeks.
Rosacea score of 3-4 as defined by the IGA scale for rosacea.
Able to have punch biopsies as described for the translational component of the study.
Able to receive VMAT RT to 36 Gy in 20 fractions in 4-8weeks for this condition.
Willing and able to give written informed consent.
Willing and able to participate in and comply with the study procedures and follow-up schedule.
Life expectancy of over 2 years.
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Rosacea where Telangiectasia is the primary feature.
Rosacea which involves the forehead.
History of a radiation sensitivity syndrome.
Previous in-field RT.
Previous in-field invasive skin cancer treated within 4 weeks of enrolment.
Human Immunodeficiency Virus infection.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be maintained via central randomisation performed on an independent web-based platform
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation will be used. Randomisation will be stratified by two severity levels of rosacea (IGA score 3 and score 4) to balance the two treatment arms for the influence of rosacea severity. Randomisation will occur in blocks of 2 or 4 (size randomly varying in 1:1 ratio) to ensure groups are as balanced as possible.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Other
Other design features
This is a parallel randomised controlled trial. However, cross-over from the standard of care arm (Dermatological standard of care treatment) to the intervention arm (VMAT Radiotherapy) will be permitted at the time of in-field failure (ie. primary endpoint being met). Cross-over is optional and at the discretion of the investigator
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The recruitment target (N=40, with 20 participants per arm) is based on evaluating the difference in proportion of patients who have failed at 12-months post-randomisation between Arm A (standard of care) and Arm B (VMAT RT). Based on the findings of a previous randomised controlled trial of Ivermectin (1%) versus metronidazole 0.75% cream for moderate to severe rosacea (Taieb et al., 2015), it is conservatively assumed that the standard of care arm (Arm A) in the current study will have a 12-month failure rate of 65%. The 12-month failure rate in the VMAT arm (Arm B) is assumed to be 20% based on a previous retrospective case series (Fogarty, 2021). Assuming a two-sided test with an alpha of 0.05 and a power of 0.80, and a drop-out rate of 10%, the required sample size is 40 patients total, randomised into two equal groups of 20.

Statistical analyses will be performed with an intention-to-treat (ITT) approach to study intervention effectiveness based on comparisons between assigned trial arms regardless of whether the participants complied with the assigned protocol or whether the treatment was given. Comparison of the primary outcome (cumulative incidence of in-field failure within 12-months of randomisation) in the intervention arm relative to the control arm will be tested using logistic regression, first univariably with group as the main fixed effect, and then multivariably to test for the possible influence of stratification factors and any important characteristics that are unbalanced between the groups at baseline.

Comparisons of secondary outcomes with count data (e.g., incidences of treatment-related toxicity at) will be performed using Poisson regression. For secondary outcomes with continuous data (e.g., QoL), comparisons will be conducted using linear regression. For concordance analysis, kappa statistics and intraclass correlation coefficients will be used to measure agreement between clinical and histopathological classification.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/10/2023
Actual
21/05/2024
Date of last participant enrolment
Anticipated
1/01/2025
Actual
Date of last data collection
Anticipated
1/01/2027
Actual
Sample size
Target
40
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23750 0
Icon Cancer Centre Revesby - Revesby
Recruitment hospital [2] 27194 0
Icon Cancer Centre Gosford - Gosford
Recruitment postcode(s) [1] 39194 0
2212 - Revesby
Recruitment postcode(s) [2] 43277 0
2250 - Gosford

Funding & Sponsors
Funding source category [1] 312270 0
Charities/Societies/Foundations
Name [1] 312270 0
Icon Cancer Foundation
Country [1] 312270 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Icon Cancer Foundation
Address
Level 1/22 Cordelia St, South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 314525 0
None
Name [1] 314525 0
Address [1] 314525 0
Country [1] 314525 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311644 0
St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC)
Ethics committee address [1] 311644 0
Ethics committee country [1] 311644 0
Australia
Date submitted for ethics approval [1] 311644 0
19/12/2022
Approval date [1] 311644 0
05/06/2023
Ethics approval number [1] 311644 0

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

Contacts
Principal investigator
Name 121830 0
Prof Gerald Fogarty
Address 121830 0
Icon Cancer Centre Revesby, 1/3 MacArthur Ave, Revesby NSW 2212
Country 121830 0
Australia
Phone 121830 0
+61 2 8722 2800
Fax 121830 0
Email 121830 0
gerald.fogarty@icon.team
Contact person for public queries
Name 121831 0
Lloyd Smyth
Address 121831 0
Icon Cancer Centre, Level 1/22 Cordelia St, South Brisbane QLD 4101
Country 121831 0
Australia
Phone 121831 0
+61 7 3737 4500
Fax 121831 0
Email 121831 0
research.iit@icon.team
Contact person for scientific queries
Name 121832 0
Gerald Fogarty
Address 121832 0
Icon Cancer Centre Revesby, 1/3 MacArthur Ave, Revesby NSW 2212
Country 121832 0
Australia
Phone 121832 0
+61 2 8722 2800
Fax 121832 0
Email 121832 0
gerald.fogarty@icon.team

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data that underlie the results reported in study-related articles
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Investigators whose proposed use of the data has ethical approval by an independent human research ethics committee, following approval of the proposal by the sponsor (Icon Cancer Foundation).
Available for what types of analyses?
To achieve the aims of the proposal
How or where can data be obtained?
Proposals should be directed to the Investigator Initiated Trials and Grants Manager (research.iit@icon.team) or the Study Chair. For accepted proposals, data will be made available to the requestor as an exported dataset from the study database.


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.