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Trial registered on ANZCTR


Registration number
ACTRN12620000955910
Ethics application status
Approved
Date submitted
29/07/2020
Date registered
25/09/2020
Date last updated
25/09/2020
Date data sharing statement initially provided
25/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
OVGUS: A study examining the use oestradiol vaginal tablets (Vagifem Low) to treat genitourinary symptoms in women on adjuvant aromatase inhibitors for breast cancer
Scientific title
OVGUS: A phase II single arm feasibility study of oestradiol vaginal tablets for genitourinary symptoms in women on adjuvant aromatase inhibitors for breast cancer
Secondary ID [1] 300708 0
None
Universal Trial Number (UTN)
Trial acronym
OVGUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vulvovaginal atrophy 317353 0
Genitourinary syndrome of menopause 317354 0
Breast cancer 317355 0
Condition category
Condition code
Reproductive Health and Childbirth 315459 315459 0 0
Menstruation and menopause
Cancer 315460 315460 0 0
Breast
Renal and Urogenital 316778 316778 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Vagifem Low 10 mcg (estradiol vaginal inserts) are small, white, film-coated tablets containing 10.3 mcg of estradiol hemihydrate equivalent to 10 mcg of estradiol. Each Vagifem Low tablet is 6 mm in diameter and is placed in a disposable applicator. Each tablet-filled applicator is packaged separately in a blister pack.
Oestradiol 10mcg vaginal pessaries (Vagifem Low) will be inserted by the participant, using an applicator, daily for the first 14 days, then twice weekly for 10 weeks (total treatment duration 12 weeks).The Vagifem Low should be inserted at night (to allow at least 12 hours before serum testing).
Adherence to the treatment will be reported by participants in a diary.
Intervention code [1] 317507 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324586 0
Adherence to treatment with vagifem low (proportion completing at least 80% of the 12 weeks of study treatment). This is assessed using a patient reported diary.
Timepoint [1] 324586 0
12 weeks post-intervention commencement
Secondary outcome [1] 385103 0
The effect of Vagifem Low on most bothersome symptom (MBS). Participants will be asked to select their most bothersome symptom at baseline. This symptom will be scored by the participant as either none, mild, moderate or severe on a study-specific questionnaire.
Timepoint [1] 385103 0
Baseline, 2 weeks post commencing Vagifem Low and 12 weeks post commencing Vagifem Low
Secondary outcome [2] 385104 0
The effect of Vagifem Low on serum highly sensitive oestradiol via liquid chromatography – mass spectrometry (LC-MS/MS)
Timepoint [2] 385104 0
Baseline, 2 weeks post commencing Vagifem Low and 12 weeks post commencing Vagifem Low
Secondary outcome [3] 385106 0
The effect of Vagifem Low on vaginal dryness. This will be reported by the participant as either none, mild, moderate or severe on a study-specific questionnaire. .
Timepoint [3] 385106 0
Baseline and 12 weeks post commencing Vagifem Low
Secondary outcome [4] 385108 0
The effect of Vagifem Low on daily function (change in Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire score )
Timepoint [4] 385108 0
Baseline and 12 weeks post commencing Vagifem Low
Secondary outcome [5] 385109 0
The effect of Vagifem Low on urinary symptoms (change in the ICIQ FLUTS score)
Timepoint [5] 385109 0
Baseline and 12 weeks post commencing Vagifem Low
Secondary outcome [6] 385110 0
The effect of Vagifem Low on QOL (change in EORTC QLC-C30)
Timepoint [6] 385110 0
Baseline and 12 weeks post commencing Vagifem Low
Secondary outcome [7] 385111 0
Adverse effects of Vagifem Low (determined by AE reporting. This will be reported using the CTCAE v5.0.

The side effects associated with oestrogens taking orally or through the skin include (all very unlikely to occur with vaginal oestrogens)::

Common side effects (seen in less than 1 in 10 people):
• Headache
• Stomach pain
• Vaginal bleeding
• Vaginal discharge
• Vaginal discomfort

Uncommon side effects (seen in between 1 in 100 to 1 in 1000 people):
• Vaginal thrush infection
• Nausea
• Rash
• Weight gain
• Hot flushes
• High blood pressure

Rare or very rare side effects (see in less than 1 in 1000 people)
• Allergic reaction
• Trouble sleeping
• Depression
• Migraines
• Deep vein thrombosis
• Diarrhoea
• Itch
• Vaginal pain
• Vaginal ulceration
• Thickening of uterus wall
• Fluid retention

There is also an increased risk of heart attack, stroke, blood clots, endometrial (uterus) and breast cancer in people taking oestrogen tablets orally. There is no evidence that vaginal oestrogens increase therisk of these conditions.
Timepoint [7] 385111 0
12 weeks post-intervention commencement
Secondary outcome [8] 385112 0
Patient acceptance (determined by a study specific questionnaire)
Timepoint [8] 385112 0
12 weeks post-treatment commencement
Secondary outcome [9] 385113 0
Compliance with aromatase inhibitor (proportion stopping or switching endocrine therapy) assessed via a study-specific questionnaire.
Timepoint [9] 385113 0
12 weeks post-treatment commencement
Secondary outcome [10] 385114 0
Fear of cancer recurrence (change in Fear of Cancer Recurrence Inventory (FCRI)
Timepoint [10] 385114 0
Baseline and 12 weeks post commencing Vagifem Low
Secondary outcome [11] 386142 0
The effect of Vagifem Low on serum highly sensitive oestriol via liquid chromatography - mass spectrometry (LC-MS/MS)
Timepoint [11] 386142 0
Baseline, 2 weeks post-treatment commencement, 12 weeks post-treatment commencement
Secondary outcome [12] 386143 0
The effect of Vagifem Low on serum FSH via immunoassay.
Timepoint [12] 386143 0
Baseline, 2 weeks post-treatment commencement and 12 weeks post-treatment commencement
Secondary outcome [13] 386144 0
The effect of Vagifem Low on vaginal itch. This will be reported by the participant as either none, mild, moderate or severe on a study-specific questionnaire. .
Timepoint [13] 386144 0
Baseline and 12 weeks post-treatment commencement
Secondary outcome [14] 386145 0
The effect of Vagifem Low on vaginal pain. This will be reported by the participant as either none, mild, moderate or severe on a study-specific questionnaire. .
Timepoint [14] 386145 0
Baseline and 12 weeks post-treatment commencement
Secondary outcome [15] 386146 0
The effect of Vagifem Low on vaginal irritation. This will be reported by the participant as either none, mild, moderate or severe on a study-specific questionnaire. .
Timepoint [15] 386146 0
Baseline and 12 weeks post-treatment commencement
Secondary outcome [16] 386147 0
The effect of Vagifem Low on pain on penetration. This will be reported by the participant as either none, mild, moderate or severe on a study-specific questionnaire. .
Timepoint [16] 386147 0
Baseline and 12 weeks post-treatment commencement
Secondary outcome [17] 386153 0
Ease of use (determined by a study specific questionnaire)
Timepoint [17] 386153 0
12 weeks post-treatment commencement

Eligibility
Key inclusion criteria
1. Women with a history of early breast cancer (stage I-III)
2. Aged 18 years or older
3. On an aromatase inhibitor +/- GNRH agonist for at least 3 months
4. Genitourinary symptoms for at least 3 months (moderate or severe for at least one of vaginal dryness, itch, pain, irritation and pain with penetration)
5. Willing and able to comply with all study requirements, including treatment (e.g. able to insert pessaries), questionnaires, blood tests
6. Written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Use of oestrogen, testosterone or progesterone therapies (systemic or vaginal) in the 4 weeks prior to study treatment
2. Active or recent genitourinary infections (<14 days)

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
60 participants will be enrolled in this feasibility study. This was determined a reasonable size pilot study to gain an understanding of patient adherence. If adherence is established a larger phase 3 trial is planned to assess efficacy of Vagifem low.
Patients who do not receive study treatment or withdraw their consent to participate prior to response evaluation will be replaced.

All analyses will include all patients who were registered.
The primary endpoint is the proportion of patients who were adherent with the study treatment (completion of at least 80% of the 12 weeks of treatment). We hypothesise that at least 70% of participants will be adherent to the study treatment and if this is achieved the primary endpoint will be met.
Statistical analysis for the various endpoints in this study will involve comparisons between baseline data and data at the two subsequent timepoints (two week visit and end of study visit). This includes analysis of data from the validated questionnaires, the study specific questionnaires and blood test results. Data will be analysed using descriptive statistics; means, medians, frequencies and proportions. Proportions will be compared using chi-squared tests.

Recruitment
Recruitment status
Not yet recruiting
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)
NSW
Recruitment hospital [1] 17166 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 17167 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 17168 0
Nepean Hospital - Kingswood
Recruitment hospital [4] 17169 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 30865 0
2560 - Campbelltown
Recruitment postcode(s) [2] 30866 0
2139 - Concord
Recruitment postcode(s) [3] 30867 0
2747 - Kingswood
Recruitment postcode(s) [4] 30868 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 305153 0
Other Collaborative groups
Name [1] 305153 0
Breast Cancer Trials
Address [1] 305153 0
Level 4, 175 Scott Street
Newcastle
NSW 2300
Country [1] 305153 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
University of Sydney
Camperdown
NSW 2006
Country
Australia
Secondary sponsor category [1] 305512 0
None
Name [1] 305512 0
Address [1] 305512 0
Country [1] 305512 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305519 0
Sydney Local Health District Research Ethics Committee - CRGH
Ethics committee address [1] 305519 0
Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139
Ethics committee country [1] 305519 0
Australia
Date submitted for ethics approval [1] 305519 0
Approval date [1] 305519 0
22/07/2020
Ethics approval number [1] 305519 0

Summary
Brief summary
This study will investigate the feasibility of using oestradiol vaginal tablets (Vagifem Low) for women on adjuvant aromatase inhibitors for breast cancer

Who is it for?
You may be eligible to join this study if you are female, aged 18 and above, have early breast cancer (stage I-III), on an aromatase inhibitor for at least 3 months and are experiencing genitourinary symtoms

Study details
All participants in this study receive estradiol vaginal pessaries (Vagifem Low) for 12 weeks (daily application for the first 14 days, then twice a week application for the next ten weeks).

Feasibility/adherence to treatment will be assessed using a participant diary. This study will also assess symptom response, quality of life and sexual function using questionnaires and the effect of this treatment on blood levels of oestrogen.

We hope this study will further medical knowledge and may improve treatment of genitourinary symptoms for women in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100650 0
Dr Belinda Kiely
Address 100650 0
NHMRC Clinical Trials Centre, Level 6, Lifehouse
119-143 Missenden Road, Camperdown NSW 2050
Locked bag 77, Camperdown NSW 1450, Australia
Country 100650 0
Australia
Phone 100650 0
+61295625000
Fax 100650 0
Email 100650 0
belinda.kiely@health.nsw.gov.au
Contact person for public queries
Name 100651 0
Dr Antonia Pearson
Address 100651 0
Bill Walsh Laboratory,
Level 8 Kolling Building
Reserve Road, St Leonards, NSW 2065
Country 100651 0
Australia
Phone 100651 0
+612 9105 5090
Fax 100651 0
Email 100651 0
antonia.pearson@sydney.edu.au
Contact person for scientific queries
Name 100652 0
Dr Antonia Pearson
Address 100652 0
Bill Walsh Laboratory,
Level 8 Kolling Building
Reserve Road, St Leonards, NSW 2065
Country 100652 0
Australia
Phone 100652 0
+612 9105 5090
Fax 100652 0
Email 100652 0
antonia.pearson@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
only researchers who provide a methodologically sound proposal
Available for what types of analyses?
only to achieve the aims in the approved proposal, for IPD meta-analysis
How or where can data be obtained?
access subject to approvals by Principal Investigator belinda.kiely@health.nsw.gov.au
What supporting documents are/will be available?
No other documents available
Summary results
No Results