GRACE-trial: a Randomized Active-controlled Trial for vulvovaGinal atRophy in breAst Cancer Patients on Endocrine Therapy. (GRACE)

September 28, 2023 updated by: University Hospital, Ghent
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Estrogen
locally administered estrogen (oestriol)
Drug: Estrogen
1 vaginal ovule daily for three consecutive weeks, followed by 1 vaginal ovule 2 times per week
Active Comparator: Dehydroepiandrosterone
locally administered dehydroepiandrosterone (DHEA)
Drug: dehydroepiandrosterone
1 vaginal ovule daily
Active Comparator: Estrogen + probiotics
locally administered estrogen (oestriol) + probiotics
Drug: Estrogen + probiotics
2 vaginal ovules daily for 5 consecutive days, repeated every 4 weeks
Active Comparator: Moisturizer
locally administered hyaluronic acid
Drug: Moisturizer
1 vaginal ovule daily for 10 consecutive days, followed by 1 vaginal ovule every three days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the EQ5D-questionnaire.
Time Frame: 12 weeks

Efficacy of the implemented treatments will be assessed based on patient-reported outcome measurements (PROM) that describe symptoms and quality-of-life.

The first primary outcome will be based on assessment using the EQ5D-questionnaire.

This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The change in these PROMs will be evaluated over the predefined timeframe of 12 weeks.

The EQ5D-questionnaire includes a scale describing the general health of the participant at the predefined times, using a metric scale from 0 to 100 (0 being the worst health and 100 being the best health).
12 weeks
Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the FACT-ES questionnaire.
Time Frame: 12 weeks

Efficacy of the implemented treatments will be assessed based on patient-reported outcome measurements (PROM) that describe symptoms and quality-of-life.

The second primary outcome will be based on assessment using the FACT-ES-questionnaire.

This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The change in these PROMs will be evaluated over the predefined timeframe of 12 weeks.

The FACT-ES consists of question with answer possibilities from 0 to 4 (with the higher the score, the better the quality of life).
12 weeks
Change in sex steroid hormone concentrations in a time frame of 12 weeks.
Time Frame: 12 weeks
The change in concentration of sex steroid hormone concentration as a surrogate for safety be be evaluated by measuring the sex hormone concentrations systemically with repeated longitudinal measurements. This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The following sex steroid hormone concentrations will be assessed: estrone, estradiol, DHEA-S, DHEA, testosterone, and dihydrotestosterone.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of vaginal microbial alterations after implementation of treatment.
Time Frame: 12 weeks
The vaginal microbiome will be determined at start and after 12 weeks. Bacterial DNA will be extracted and the microbiota will be identified using cpn60 sequencing. The change in microbial profiles between the two timepoints will be assessed.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Ghent

Collaborators

University Ghent

Investigators

  • Principal Investigator: Hans Verstraelen, MD, PhD, University Hospital, Ghent

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2022

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

February 7, 2022

First Submitted That Met QC Criteria

September 28, 2022

First Posted (Actual)

September 30, 2022

Study Record Updates

Last Update Posted (Actual)

September 29, 2023

Last Update Submitted That Met QC Criteria

September 28, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BC-09638

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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