Clinical trial NCT05562518: GRACE-trial: a Randomized Active-controlled Trial for VulvovaGinal AtRophy in BreAst Cancer Patients on Endocrine Therapy.
Official title: GRACE-trial: a Randomized Active-controlled Trial for VulvovaGinal AtRophy in BreAst Cancer Patients on Endocrine Therapy.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Vulvovaginal Atrophy
Breast Cancer
Keywords: breast cancer
vulvovaginal atrophy
endocrine therapy
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: University Ghent
First posted: 2022-09-30
Enrollment: 160
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this prospective active-controlled randomized trial the investigators will assess for the first time ever the different local treatments of vulvovaginal atrophy in breast cancer patients on endocrine therapy. These patients are currently inadequately treated based on ignorance of possible treatment modalities and stigmatization of vulvovaginal atrophy.

Detailed description: In this prospective active-controlled randomized trial the investigators will assess for the first time ever the different local treatments of vulvovaginal atrophy in breast cancer patients on endocrine therapy. These patients are currently inadequately treated based on ignorance of possible treatment modalities and stigmatization of vulvovaginal atrophy.

While current knowledge on comparative data of the local treatments of vulvovaginal atrophy is based on retrospective data or one-to-one comparisons, we will prospectively evaluate all different local treatments based on patient-reported outcome measurements. This new data is mandatory for increasing the awareness of physicians of the treatment possibilities of vulvovaginal atrophy in breast cancer patients. Together with the use of different communication channels towards patients, this combination will substantially contribute to the increase of quality-of-life of breast cancer patients with vulvovaginal atrophy.

The primary objectives in this trial are two-fold. The first primary objective addresses the efficacy of the different implemented treatment strategies based on patient-reported outcome measurements (PROMs). These PROMs will be implemented prior to treatment and after initiation of the implemented treatments (estrogen, DHEA, probiotics or moisturizer). By implementing repeated PROM assessment, longitudinal evaluation of symptom alterations due to the treatment can be objectified.

The second primary objective is the safety evaluation of the implemented treatments. This evaluation will be achieved by measuring the sex hormone concentrations systemically with repeated longitudinal measurements.

In this study, the investigators will measure sex hormone concentrations through high-sensitive assessments based on LC-MS/MS. Considering the ALARA (as low a reasonably achievable) principle in radiation safety, we could extrapolate this ALARA principle to the safety of the local hormonal treatment of vulvovaginal atrophy in breast cancer patients, where potential differences in increase of sex hormone concentrations between the different treatment modalities could be objectified. Despite previous literature that could not show increased recurrence of breast cancer, this finding will play an import role in the decision-making of treatment of vulvovaginal atrophy in breast cancer patients. As mentioned earlier, a direct comparison of these sex hormone concentrations for the different treatment modalities is currently lacking.

As translational secondary objective, the investigators aim to investigate the microbial alterations when using local treatment for vulvovaginal atrophy. Identification of these alterations will contribute in understanding the pathophysiology of vulvovaginal atrophy and may unravel changes caused by the local treatment and may create opportunities in the future for additive treatment or new therapeutic strategies to ameliorate the quality-of-life of breast cancer patients with vulvovaginal atrophy.

Eligibility criteria: Inclusion Criteria:

* breast cancer patient
* current endocrine therapy (AI or SERM)
* postmenopausal status, defined by:

  * 12 months amenorrhoea or
  * 6 months amenorrhoe and FSH level of \>40 mIU/mL or

    \*\>6 weeks after bilateral oophorectomy or
  * induced postmenopause (ovarian function suppression using GnRH-analogue)
* presence of one or more symptoms of vulvovaginal atrophy (dyspareunia, dryness, irritation)

Exclusion Criteria:

* a history of vulvar or vaginal surgery
* current other vulvar or vaginal disease
* recent use of antibiotics/antifungals/corticosteroids (less than 1 month)
* current use of vaginal hormonal treatment or vaginal moisturizer: inclusion is possible after a washout period of 4 weeks

Primary outcomes:
measure: Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the EQ5D-questionnaire.
timeFrame: 12 weeks
measure: Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the FACT-ES questionnaire.
timeFrame: 12 weeks
measure: Change in sex steroid hormone concentrations in a time frame of 12 weeks.
timeFrame: 12 weeks
Secondary outcomes:
measure: Identification of vaginal microbial alterations after implementation of treatment.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: University Hospital Ghent
Study officials:
affiliation: University Hospital, Ghent
name: Hans Verstraelen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: