GRACE-trial: a Randomized Active-controlled Trial for vulvovaGinal atRophy in breAst Cancer Patients on Endocrine Therapy.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the EQ5D-questionnaire.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •a history of vulvar or vaginal surgery (Inclusion is possible after hysterectomy. For these subjects no microbiome sampling will be performed. Microbiome analysis is not performed for these subjects.)
- •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
研究组 & 干预措施
Dehydroepiandrosterone
locally administered dehydroepiandrosterone (DHEA)
干预措施: dehydroepiandrosterone (Drug)
Estrogen
locally administered estrogen (oestriol)
干预措施: Estrogen (Drug)
Estrogen + probiotics
locally administered estrogen (oestriol) + probiotics
干预措施: Estrogen + probiotics (Drug)
Moisturizer
locally administered hyaluronic acid
干预措施: Moisturizer (Drug)
结局指标
主要结局
Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the EQ5D-questionnaire.
时间窗: 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).
Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the FACT-ES questionnaire.
时间窗: 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).
Change in sex steroid hormone concentrations in a time frame of 12 weeks.
时间窗: 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.
次要结局
- Identification of vaginal microbial alterations after implementation of treatment.(12 weeks)