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Trial registered on ANZCTR


Registration number
ACTRN12615000083594
Ethics application status
Approved
Date submitted
6/01/2015
Date registered
2/02/2015
Date last updated
22/11/2019
Date data sharing statement initially provided
22/11/2019
Date results information initially provided
22/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Sexual Well Being After Breast cancer study - SWAB study
Scientific title
Efficacy and safety of intra-vaginal testosterone for the treatment of vulvo-vaginal atrophy (VVA) associated with aromatase inhibitor therapy in women with breast cancer.
Secondary ID [1] 285915 0
nil
Universal Trial Number (UTN)
Trial acronym
SWAB study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vulvovaginal Atrophy 293833 0
Breast cancer 293962 0
Condition category
Condition code
Renal and Urogenital 294135 294135 0 0
Other renal and urogenital disorders
Cancer 294259 294259 0 0
Breast
Reproductive Health and Childbirth 294260 294260 0 0
Menstruation and menopause

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
300mcg intravaginal testosterone cream will be compounded in the Professional Compounding Centers of America brand Versabase Cream as the base. Application dosing is nightly for 2 weeks then nightly three times a week for 24 weeks. Compliance to treatment will be the use of at least 75% of the medication in each 13 week period ( assessed by weight)
Intervention code [1] 290890 0
Treatment: Drugs
Comparator / control treatment
The placebo cream will be the Professional Compounding Centers of America brand Versabase Cream
Control group
Placebo

Outcomes
Primary outcome [1] 293937 0
Assessment of the efficacy of intravaginal testosterone therapy, for the treatment of sexual dysfunction due to vulvo vaginal atrophy in women who have symptoms estrogen insufficiency having treatment of breast cancer with an aromatase inhibitor (AI) as assessed by the satisfaction domain of the Female Sexual Function Index
Timepoint [1] 293937 0
26 weeks
Secondary outcome [1] 312179 0
Assessment of sexual wellbeing as assessed by
a) the total score of the Female Sexual Function Index ( FSFI)
b) the subdomains of desire, arousal, orgasm, satisfaction and sexual pain
c) distress associated with female sexual dysfunction measured by the Female Sexual Distress Scale- revised ( FSDS-R)
Timepoint [1] 312179 0
26 weeks
Secondary outcome [2] 312180 0
Indices of vaginal health as assessed by: a) Atrophic vaginitis assessed by clinical examination b) Change in vaginal pH c) Change in the proportion of vaginal parabasal and superficial cells d)the Profile of Female Sexual Function (PFSP) questionnaire
Timepoint [2] 312180 0
26 weeks
Secondary outcome [3] 312181 0
The presence of urinary incontinence as assessed by the Questionnaire for Urinary Incontinence Diagnosis (QUID)
Timepoint [3] 312181 0
26 weeks
Secondary outcome [4] 312182 0
The circulating levels of Estradiol, Estrone, Testosterone, Dihydrotestosterone and their metabolites by liquid chromatography mass spectrometry (LCMS).
Timepoint [4] 312182 0
26 weeks

Eligibility
Key inclusion criteria
Women:
1. Who are aged over 18 years with invasive breast cancer treated with an AI
2. Who are experiencing at least one symptom of vaginal dryness, itch causing pain with sexual activity for which they seek treatment.
3. Have less than 5% superficial cells on vaginal smear
4. Have a vaginal pH above 5
5. Have a clinically acceptable Papanicolaou smear (no evidence of malignancy or squamous intraepithelial lesions) within the past 2 years if the cervix is present
6. Have a clinically acceptable mammogram if 50 years or older as per the management of their breast specialist (oncologist or surgeon).
7. who are able and willing to participate in the study as evidenced by providing written consent
Minimum age
18 Years
Maximum age
70 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Women who have:

a) undiagnosed genital bleeding
b) used vaginal hormonal products (rings, creams, or gels) in the past month
c) sexual dysfunction caused by another medical condition
d) used systemic sex steroid therapy (estrogen, testosterone, tibolone or dehydroepiandrosterone) in the preceding 6 months.
e) renal disease, history of cerebrovascular disease, thrombo-embolic disorders, myocardial infarction or angina at any time before study entry or thrombo-phlebitis within the last 5 years, or any other major illness that has occurred within the last 6 months.
f) hypertension equal to or above 160/95 mm Hg
g) Significant gastrointestinal, liver or gall bladder disease
h) a condition known to affect steroid metabolism or taken therapy known to affect steroid metabolism other than the AI therapy for breast cancer (eg, clomiphene, testolactone, ketoconazole, spironolactone, histamine 2 [Histamine 2 receptor blockers, etc.])
i) a previous diagnosis of cancer, except non melanotic skin cancer
j) moderate to severe acne or hirsutism, have used anti-androgen therapy for acne or hirsutism in the preceding 5 years, or who have androgenic alopecia (we will exclude women with clinically meaningful androgen excess)
k) have a history of, or current evidence of, abuse of alcohol or any drug substance or be a regular drinker of more than 3 standard drinks per day

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)
Participants will be recruited through oncologists, breast specialists and the Breast Cancer Network of Australia. They will beinvited to contact the Women’s Health Research Program (WHRP). If eligible to participate they will attend the WHRP for 4 visits.

Each participant will be given a unique two-digit participant screening number in sequential ascending order at the Screening visit. Participants will receive these numbers in the order in which they enter the study and they will retain this number throughout their participation in the study.

Participants who meet inclusion/exclusion criteria will be assigned a Randomization Number. The randomization code will be generated independently by the Department of Epidemiology and Preventive Medicine, Monash University and randomization and packaging will be undertaken by the compounding pharmacy in the Alfred Hospital, Melbourne.
The participant will receive study drug with their unique Randomization number.

Treatment randomization will occur 4-6 weeks after screening.

All investigators and clinical staff will remain blinded to allocation of therapy until the statistical data base is cleaned and locked.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Analysis by intention to treat including anyone who receives at least one dose of treatment and has any follow-up data collected.
The primary outcome variable is the satisfaction domain of the FSFI which has 6 domain scores and an overall score (the overall score is a weighted sum of the domain scores). This is the primary outcome as satisfaction is the domain of greatest clinical relevance.
Based on the paper by Fernandes et al, the following differences were observed between the mean scores for the lubricant (placebo) and testosterone groups at 12 weeks.
Based on a comparison of means in the satisfaction domain, the estimated sample size would be 21 in each group. (2x 10.5) as the difference between means and the SD were equivalent.
However, even though satisfaction is our primary clinical concern, we do not want to have inadequate power to assess the other domains.

To allow for dropouts we will recruit 50 women to each group.

If a significant difference was seen between groups at 26 weeks, then an analysis would be done at 12 weeks to see if the difference was already detectable at that point- this is for timing only. If no such difference was seen at 26 weeks, the 12 week analysis would not proceed. For this reason, we do not need to adjust the 26 week analysis for multiple comparisons.
For all domains, for the final analysis it may be appropriate to adjust the mean scores at 26 weeks for the baseline mean score.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 9083 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 290496 0
University
Name [1] 290496 0
Monash University
Address [1] 290496 0
99 Commercial Rd
Melbourne 3004
VIC
Country [1] 290496 0
Australia
Primary sponsor type
University
Name
Monash University
Address
99 Commercial Rd
Melbourne 3004
VIC
Country
Australia
Secondary sponsor category [1] 289195 0
None
Name [1] 289195 0
Address [1] 289195 0
Country [1] 289195 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292153 0
Monash University Human Research Ethics
Ethics committee address [1] 292153 0
Human Ethics Office
First Floor, Building 3e
Room 111
Monash Research Office
Clayton Campus
Monash University VIC 3800

Ethics committee country [1] 292153 0
Australia
Date submitted for ethics approval [1] 292153 0
27/01/2015
Approval date [1] 292153 0
18/02/2015
Ethics approval number [1] 292153 0
2014002067

Summary
Brief summary
This study will determine the effectiveness of intravaginal testosterone cream therapy for the treatment of sexual dysfunction due to Genitourinary Syndrome of Menopause (GSM) in women with breast cancer being treated with an aromatase inhibitor (AI). Who is it for? You may be eligible to join this study if you are aged 18 years or above, have been diagnosed with invasive breast cancer, currently being treated with an AI and experiencing at least one symptom of vaginal dryness, itch, or pain with sexual activity for which you are seeking treatment Study details -participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will apply the intravaginal testosterone cream, whilst participants in the other group will apply the intravaginal placebo cream. Both groups will apply the creams nightly for the first two weeks and then nightly 3 times a week for the remaining 24 weeks. Circulating levels of hormones will be checked before, during and at the end of the treatment period and participants will be asked to answer questionnaires related to sexual function.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53806 0
Prof Susan Davis
Address 53806 0
Women's Health Research Program Monash University Level 6, The Alfred
Centre 99 Commercial Rd Melbourne Victoria 3004
Country 53806 0
Australia
Phone 53806 0
+61 3 9903 0827
Fax 53806 0
+61 3 9903 0828
Email 53806 0
susan.davis@monash.edu
Contact person for public queries
Name 53807 0
Prof Susan Davis
Address 53807 0
Women's Health Research Program Monash University Level 6, The Alfred
Centre 99 Commercial Rd Melbourne Victoria 3004
Country 53807 0
Australia
Phone 53807 0
+61 3 9903 0827
Fax 53807 0
+61 3 9903 0828
Email 53807 0
susan.davis@monash.edu
Contact person for scientific queries
Name 53808 0
Prof Susan Davis
Address 53808 0
Women's Health Research Program Monash University Level 6, The Alfred
Centre 99 Commercial Rd Melbourne Victoria 3004
Country 53808 0
Australia
Phone 53808 0
+61 3 9903 0827
Fax 53808 0
+61 3 9903 0828
Email 53808 0
susan.davis@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 5810 0
J Clin Endocrinol Metab. 2018 Nov 1;103(11):4146-4154. doi: 10.1210/jc.2018-01345.
Intravaginal Testosterone Improves Sexual Satisfaction and Vaginal Symptoms Associated With Aromatase Inhibitors.
Davis SR, Robinson PJ, Jane F, White S2, White M, Bell RJ.
Attachments [1] 5810 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary